Structural covariance network activity in the medial prefrontal cortex is modulated by childhood abuse in adolescents with depression.

Aberrant structural covariance (SC) in the medial prefrontal cortex (mPFC) is believed to play a crucial role in adolescent-onset major depressive disorder (AO-MDD). However, the effect of childhood abuse (CA) on SC in AO-MDD patients is still unknown. Here, we measured anomalous SC in the mPFC of AO-MDD patients and assessed the potential modulation of this feature by CA. We acquired T1-weighted structural images of AO-MDD patients (n = 93) and healthy controls (HCs, n = 81). Using voxel-based morphometry analysis, we calculated gray matter volumes for each subject. Subsequently, we classified abnormal SC in the mPFC into three subtypes according to overall CA. Compared with HCs, AO-MDD patients showed alterations in the structural covariance network of the mPFC, which is a central region in the default mode network (DMN). We also found an anterior-posterior dissociation in the structural covariance connectivity of the DMN. A history of CA modulated bilateral mPFC SC. These changes were primarily focused on the SC between the mPFC and the limbic system, indicating a gap in the rate of neural maturation between these regions. In summary, the DMN and frontal-limbic system, which are involved in emotional processing, appear to play a significant role in the development of AO-MDD. These findings highlight the crucial effects of CA on neurophysiological alterations in individuals with AO-MDD.

Non-improvement predicts subsequent non-response to repeated-dose intravenous ketamine for depression: a re-analysis of a 2-week open-label study in patients with unipolar and bipolar depression.

There is insufficient evidence to guide dose and frequency optimization with repeated-dose ketamine for depression. This study assessed the value of symptomatic non-improvement after the first few ketamine infusions as a predictor of overall non-response in depression for early decision-making to discontinue treatment. A total of 135 individuals with major depressive disorder or bipolar disorder experiencing a current major depressive episode were administered six repeated doses of intravenous ketamine. Depressive symptoms were assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS) at baseline, 4 h after the first infusion, and 24 h after each infusion. Improvement, partial response, and response were defined as a reduction rate of ≥ 20%, 30%, and 50% in MADRS scores, respectively. This study examined the relationship between improvement (as opposed to non-improvement after each infusion or consecutive non-improvements after the first few infusions) and partial response and response after the sixth infusion. This analysis was summarized using sensitivity, specificity, and other diagnostic test parameters. The sensitivities of improvement at 24 h post-infusion 4 and improvement at 24 h post-infusion 3, vs. three consecutive non-improvements, as predictors for overall partial response and response exceeded 90%. No significant reduction in depressive symptoms was seen in non-improvers following the remaining infusions after the above-identified point. Our study suggests that non-improvement after four infusions, or more conservatively three consecutive non-improvements after three infusions, could serve as a signal of overall non-response to repeated-dose intravenous ketamine for depression and that subsequent treatments would not be warranted.

A genome and gene catalog of the aquatic microbiomes of the Tibetan Plateau.

The Tibetan Plateau supplies water to nearly 2 billion people in Asia, but climate change poses threats to its aquatic microbial resources. Here, we construct the Tibetan Plateau Microbial Catalog by sequencing 498 metagenomes from six water ecosystems (saline lakes, freshwater lakes, rivers, hot springs, wetlands and glaciers). Our catalog expands knowledge of regional genomic diversity by presenting 32,355 metagenome-assembled genomes that de-replicated into 10,723 representative genome-based species, of which 88% were unannotated. The catalog contains nearly 300 million non-redundant gene clusters, of which 15% novel, and 73,864 biosynthetic gene clusters, of which 50% novel, thus expanding known functional diversity. Using these data, we investigate the Tibetan Plateau aquatic microbiome's biogeography along a distance of 2,500 km and >5 km in altitude. Microbial compositional similarity and the shared gene count with the Tibetan Plateau microbiome decline along with distance and altitude difference, suggesting a dispersal pattern. The Tibetan Plateau Microbial Catalog stands as a substantial repository for high-altitude aquatic microbiome resources, providing potential for discovering novel lineages and functions, and bridging knowledge gaps in microbiome biogeography.

NEFA can serve as good biological markers for the diagnosis of depression in adolescents.

BACKGROUND: The incidence of adolescent depression has markedly risen in recent years, with a high recurrence rate into adulthood. Diagnosis in adolescents is challenging due to subjective factors, highlighting the crucial need for objective diagnostic markers. METHODS: Our study enrolled 204 participants, including healthy controls (n = 88) and first-episode adolescent depression patients (n = 116). Serum samples underwent gas chromatography-mass spectrometry (GC-MS) analysis to assess non-esterified fatty acids (NEFA) expression. Machine learning and ROC analysis were employed to identify potential biomarkers, followed by bioinformatics analysis to explore underlying mechanisms. RESULTS: Nearly all differentially expressed NEFA exhibited significant downregulation. Notably, nonanoic acid, cis-10-pentadecenoic acid, cis-10-carboenoic acid, and cis-11-eicosenoic acid demonstrated excellent performance in distinguishing adolescent depression patients. Metabolite-gene interaction analysis revealed these NEFAs interacted with multiple genes. KEGG pathway analysis on these genes suggested that differentially expressed NEFA may impact PPAR and cAMP signaling pathways. LIMITATIONS: Inclusion of diverse populations for evaluation is warranted. Biomarkers identified in this study require samples that are more in line with the experimental design for external validation, and further basic research is necessary to validate the potential depressive mechanisms of NEFA. CONCLUSIONS: The overall reduction in NEFA expression in first-episode adolescent depression patients suggests a potential mediation of depression symptoms through cAMP and PPAR signaling pathways. NEFA levels show promise as a diagnostic tool for identifying first-episode adolescent depression patients.

Long-term quality of life after repeated ketamine infusions in anxious and nonanxious patients with depression.

BACKGROUND: There have been many studies on the benefits of repeated ketamine infusions on patients' depression but few on the impact of ketamine on patients' long-term quality of life (QoL). This study investigated long-term QoL in individuals with depression, both anxious and nonanxious. METHODS: A total of 107 individuals with a diagnosis of depression were included in the study. The patients were evaluated on Days 0, 13 and 26 and Months 6 and 9, and they received six ketamine infusions over the course of two weeks. The World Health Organization Quality of Life-BREF (WHOQOL-BREF) Scale and the Patient Health Questionnaire-9 (PHQ-9) Scale were used to measure depressive symptoms and QoL. Linear mixed models were used to evaluate depressive symptoms and QoL during ketamine treatment. RESULTS: A total of 67.2 % of patients were diagnosed with anxious depression. In the long term, there were no significant differences in the time-by-group interactions for general QoL (F = 0.510; P = 0.676), physical QoL (F = 2.092; P = 0.102), psychological QoL (F = 0.102; P = 0.959), social QoL (F = 2.180; P = 0.091), or environmental QoL (F = 1.849; P = 0.139) between the two groups. LIMITATIONS: The main limitation of this study is its open-label design. CONCLUSION: The improvement in depression symptoms and QoL following ketamine treatment was not impacted by the presence or absence of anxiety in patients who were depressed prior to treatment. Only occasionally did depressed individuals with anxiety experience a worsening of their quality of life compared to those without anxiety.

IPAC integrates rewarding and environmental memory during the acquisition of morphine CPP.

The association between rewarding and drug-related memory is a leading factor for the formation of addiction, yet the neural circuits underlying the association remain unclear. Here, we showed that the interstitial nucleus of the posterior limb of the anterior commissure (IPAC) integrated rewarding and environmental memory information by two different receiving projections from ventral tegmental area (VTA) and nucleus accumbens shell region (NAcSh) to mediate the acquisition of morphine conditioned place preference (CPP). A projection from the VTA GABAergic neurons (VTAGABA) to the IPAC lateral region GABAergic neurons (IPACLGABA) mediated the effect of morphine rewarding, whereas the pathway from NAcSh dopamine receptor 1-expressing neurons (NAcShD1) to the IPAC medial region GABAergic neurons (IPACMGABA) was involved in the acquisition of environmental memory. These findings demonstrated that the distinct IPAC circuits VTAGABA→IPACLGABA and NAcShD1R→IPACMGABA were attributable to the rewarding and environmental memory during the acquisition of morphine CPP, respectively, and provided the circuit-based potential targets for preventing and treating opioid addiction.

Mapping metabolite change in the mouse brain after esketamine injection by ambient mass spectrometry imaging and metabolomics.

Ketamine is a new, fast, and effective antidepression treatment method; however, the possible dissociation effects, sensory changes, abuse risk, and the inability to accurately identify whether patients have a significant response to ketamine limit its clinical use. Further exploration of the antidepressant mechanisms of ketamine will contribute to its safe and practical application. Metabolites, the products of upstream gene expression and protein regulatory networks, play an essential role in various physiological and pathophysiological processes. In traditional metabonomics it is difficult to achieve the spatial localization of metabolites, which limits the further analysis of brain metabonomics by researchers. Here, we used a metabolic network mapping method called ambient air flow-assisted desorption electrospray ionization (AFADESI)-mass spectrometry imaging (MSI). We found the main changes in glycerophospholipid metabolism around the brain and sphingolipid metabolism changed mainly in the globus pallidus, which showed the most significant metabolite change after esketamine injection. The spatial distribution of metabolic changes was evaluated in the whole brain, and the potential mechanism of esketamine's antidepressant effect was explored in this research.

NFATc2-dependent epigenetic downregulation of the TSC2/Beclin-1 pathway is involved in neuropathic pain induced by oxaliplatin.

Neuropathic pain is a common dose-limiting side effect of oxaliplatin, which hampers the effective treatment of tumors. Here, we found that upregulation of transcription factor NFATc2 decreased the expression of Beclin-1, a critical molecule in autophagy, in the spinal dorsal horn, and contributed to neuropathic pain following oxaliplatin treatment. Meanwhile, manipulating autophagy levels by intrathecal injection of rapamycin (RAPA) or 3-methyladenine (3-MA) differentially altered mechanical allodynia in oxaliplatin-treated or naïve rats. Utilizing chromatin immunoprecipitation-sequencing (ChIP-seq) assay combined with bioinformatics analysis, we found that NFATc2 negatively regulated the transcription of tuberous sclerosis complex protein 2 (TSC2), which contributed to the oxaliplatin-induced Beclin-1 downregulation. Further assays revealed that NFATc2 regulated histone H4 acetylation and methylation in the TSC2 promoter site 1 in rats' dorsal horns with oxaliplatin treatment. These results suggested that NFATc2 mediated the epigenetic downregulation of the TSC2/Beclin-1 autophagy pathway and contributed to oxaliplatin-induced mechanical allodynia, which provided a new therapeutic insight for chemotherapy-induced neuropathic pain.

Protocol for LaSmZrO/YSZ/NiCoCrAlYHf thermal barrier coatings using arc ion-plating and electron-beam physical vapor deposition.

Re-La2Zr2O7 are promising candidates to substitute Y2O3-stabilized ZrO2 (YSZ) in gas turbine engines. Here, we present a protocol for the deposition of LaSmZrO/YSZ/NiCoCrAlYHf thermal barrier coatings via arc ion-plating physical vapor deposition (AIP-PVD) and electron-beam physical vapor deposition (EB-PVD) technique. We describe the steps for specimen preparation via polishing and grit blasting and detail NiCoCrAlYHf bond coatings deposition via AIP-PVD and LaSmZrO and YSZ ceramic coatings deposition via EB-PVD. This protocol can be expanded to other multi-layer coatings deposition. For complete details on the use and execution of this protocol, please refer to Shen et al. (2022a).

Thermal property and failure behavior of LaSmZrO thermal barrier coatings by EB-PVD.

La2Zr2O7 coatings are promising candidates to substitute YSZ coatings in advanced gas turbine engines. In this work, Sm-doped La2Zr2O7 coatings were deposited by physical vapor deposition. This work focuses on the crystal structure, thermal conductivity, thermal expansion coefficient, morphology, composition, and thermal durability of LaSmZrO coatings. The LaSmZrO ceramics exhibit low thermal conductivity (1.69 W/mK at 800°C) and high thermal expansion coefficient (9.72∗10-6 K-1 at 1500°C) compared with La2Zr2O7. The LaSmZrO/YSZ coatings with feathery microstructure show relatively good thermal durability (8183 cycles or 856 h) under high temperature. The broken regions are observed at the ceramic coating/bond coating interface. The failure behaviors are relevant with crack evolution and thermally grown oxide growth. This work might guide the investigation of advanced coatings under high temperature.

Design and implementation of a highly integrated dual hemisphere capsule robot.

To achieve cancer screening in any appointed position in 3D regions of the gastrointestinal (GI) tract such as esophagus, stomach and colon, a highly integrated dual hemisphere capsule robot (DHCR) with a novel three-layer nested structure is proposed. Based on tracking effect, in which the robotic axis is likely to be approximately coincident with the orientation of the space universal rotating magnetic field (SURMF) using the gyroscope dynamic balance, the dual hemisphere structure realizes the observation at a fixed-point in the passive mode and the rolling locomotion in the active mode by the dynamic posture control of the SURMF manipulation. The image acquisition module, wireless transmission module and driving actuator are tuned in a spherical structure, making the DHCR more compact and less invasive. To verify the maneuverability of the innovative DHCR both for observation at a fixed-point and navigation in curved intestine by aid of image, experiments are conducted in the simulated GI tract environment. The results show that the DHCR achieves effective conversion between posture adjustment and rolling locomotion, which lays a foundation for all-over inspection and medical operation inside 3D regions of the GI tract of human body.

Posture Dynamic Modeling and Stability Analysis of a Magnetic Driven Dual-Spin Spherical Capsule Robot.

In order to realize the intervention operation in the unstructured and ample environments such as stomach and colon, a dual-spin spherical capsule robot (DSCR) driven by pure magnetic torque generated by the universal rotating magnetic field (URMF) is proposed. The coupled magnetic torque, the viscoelastic friction torque, and the gravity torque were analyzed. Furthermore, the posture dynamic model describing the electric-magnetic-mechanical-liquid coupling dynamic behavior of the DSCR in the gastrointestinal (GI) tract was established. This model is a second-order periodic variable coefficient dynamics equation, which should be regarded as an extension of the Lagrange case for the dual-spin body system under the fixed-point motion, since the external torques were applied. Based on the Floquet-Lyapunov theory, the stability domain of the DSCR for the asymptotically stable motion and periodic motion were obtained by investigating the influence of the angular velocity of the URMF, the magnetic induction intensity, and the centroid deviation. Research results show that the DSCR can realize three kinds of motion, which are asymptotically stable motion, periodic motion, and chaotic motion, according to the distribution of the system characteristic multipliers. Moreover, the posture stability of the DSCR can be improved by increasing the angular velocity of the URMF and reducing the magnetic induction intensity.

Epigenetic upregulation of hippocampal CXCL12 contributes to context spatial memory-associated morphine conditioning.

Conditioned place preference (CPP) is a learned behavior, in which animals learn to associate environmental contexts with rewarding effects. The formation of CPP is an integrated outcome of multiple learning processes. Although multiple anatomical substrates underlying this contextual learning have been proposed, it remains unknown whether a specific molecular signaling pathway within CA1 mediates context learning associated with morphine conditioning. Here, we showed that repeated context learning associated with morphine conditioning significantly increased CXCL12 levels in hippocampal CA1 neurons, and the inhibition of CXCL12 expression ameliorated the CPP behavior following context exposure with morphine conditioning. Additionally, repeated context exposure with morphine conditioning increased the phosphorylation of STAT3 and the acetylation of histone H4 in CXCL12-expressing neurons in CA1. Immunoprecipitation and chromatin immunoprecipitation assays demonstrated that repeated context exposure with morphine conditioning increased the binding of STAT3 to the CXCL12 gene promoter and the interaction between STAT3 and p300, which contributed to the enhanced transcription of CXCL12 by increasing the acetylation of histone H4 in the CXCL12 gene promoter. The inhibition of STAT3 by intrathecal injection of S3I-201 suppressed the acetylation of histone H4. These data demonstrated the epigenetic upregulation of CXCL12 following repeated context exposure with morphine conditioning, which potentially contributed to the spatial memory consolidation associated with conditioned place preference induced by morphine conditioning.

[Near-infrared luminescence and energy transfer of ACaPO4 : Eu2+, Nd3+ (A = Li, K, Na)].

Near-infrared (NIR) luminescence phosphors ACaPO4 : Eu2+, Nd2+ (A = Li, K, Na) were prepared by conventional solid state method and the sensitization of Nd3+ near-infrared luminescence by Eu2+ was investigated. The characteristic NIR luminescence of Nd3+ in ACaPO4 matrix is greatly enhanced by co-doping of Eu2+. The fluorescence properties of ACaPO4 : Eu2+, the NIR luminescence properties of ACaPO4 : Eu2+, Nd3+ and the fluorescence lifetime were studied. The effect of emission wavelength of Eu2+ on NIR luminescence of Nd3+ was investigated; The energy transfer mechanism between Eu2+ and Nd3+ was also discussed. Emission peak wavelength of Eu2+ In ACaPO4 matrixes was found red shift with the series of A = Li, K, Na and the extent of the overlap with the different excitation peaks of Nd3+ changes obviously. It was concluded that the emission peak position of Eu2+ is a very important factor for energy transfer, and the optimal wavelength range for Eu2+ --> Nd3+ energy transfer is 500 to 550 nm.