Interactive effect of air pollution and genetic risk of depression on processing speed by resting-state functional connectivity of occipitoparietal network.

BACKGROUND: Air pollution, a reversible environmental factor, was significantly associated with the cognitive domains that are impaired in major depressive disorder (MDD), notably processing speed. Limited evidence explores the interactive effect of air pollution and the genetic risk of depression on cognition. This cross-sectional study aims to extend the research by specifically examining how this interaction influences depression-related cognitive impairment and resting-state brain function. METHODS: Eligible participants were 497 healthy adult volunteers (48.7% males, mean age 24.5) living in Beijing for at least 1 year and exposed to relatively high air pollution from the local community controlling for socioeconomic and genomic. Six months' ambient air pollution exposures were assessed based on residential addresses using monthly averages of fine particulate matter with a diameter of less than or equal to 2.5 µm (PM2.5). A cross-sectional analysis was conducted using functional magnetic resonance imaging (fMRI) and cognitive performance assessments. The polygenic risk score (PRS) of MDD was used to estimate genetic susceptibility. RESULTS: Using a general linear model and partial least square regression, we observed a negative association between resting-state local connectivity in precuneus and PRS-by-PM2.5 interactive effect (PFWE = 0.028), indicating that PM2.5 exposure reduced the spontaneous activity in precuneus in individuals at high genetic risk for MDD. DNA methylation and gene expression of the SLC30A3 gene, responsible for maintaining zinc-glutamate homeostasis, was suggestively associated with this local connectivity. For the global functional connectivity, the polygenic risk for MDD augmented the neural impact of PM2.5 exposure, especially in the frontal-parietal and frontal-limbic regions of the default mode network (PFDR < 0.05). In those genetically predisposed to MDD, increased PM2.5 exposure positively correlated with resting-state functional connectivity between the left angular gyrus and left cuneus gyrus. This connectivity was negatively associated with processing speed. CONCLUSIONS: Our cross-sectional study suggests that air pollution may be associated with an increased likelihood of cognitive impairment in individuals genetically predisposed to depression, potentially through alterations in the resting-state function of the occipitoparietal and default mode network.

Spontaneous formation of MXene-oxidized sono/chemo-dynamic sonosensitizer/nanocatalyst for antibacteria and bone-tissue regeneration.

Prolonged and incurable bacterial infections in soft tissue and bone are currently causing large challenges in the clinic. Two-dimensional (2D) materials have been designed to address these issues, but materials with satisfying therapeutic effects are still needed. Herein, CaO2-loaded 2D titanium carbide nanosheets (CaO2-TiOx@Ti3C2, C-T@Ti3C2) were developed. Surprisingly, this nanosheet exhibited sonodynamic ability, in which CaO2 caused the in situ oxidation of Ti3C2 MXene to produce acoustic sensitiser TiO2 on its surface. In addition, this nanosheet displayed chemodynamic features, which promoted a Fenton reaction triggered by self-supplied H2O2. We detected that C-T@Ti3C2 nanosheets increased reactive oxygen species (ROS) production in response to sonodynamic therapy, which displayed an ideal antibacterial effect. Furthermore, these nanoreactors facilitated the deposition of Ca2+, which promoted osteogenic transformation and enhanced bone quality in osteomyelitis models. Herein, a wound healing model and prosthetic joint infection (PJI) model were established, and the C-T@Ti3C2 nanosheets played a protective role in these models. Taken together, the results indicated that the C-T@Ti3C2 nanosheets function as a multifunctional instrument with sonodynamic features, which might reveal information regarding the treatment of bacterial infections during wound healing.

The association between childhood trauma and pain symptoms in depressed adults: The moderating role of anxious attachment.

Studies have previously demonstrated that anxious attachment shapes the association between childhood traumatic experiences and somatic pain; however, it remains unclear how this relationship is influenced by anxious attachment in patients with depression. This study investigated how anxious attachment influences the relationship between childhood traumatic experiences and pain symptoms in depressed patients from a social psychological perspective. A total of 139 adult patients with depression participated in this study; the level of depression was assessed by a psychiatric professional. Childhood trauma, pain symptoms, and attachment dimensions were tested by various questionnaires. The moderating role of anxious attachment in the trauma-pain association was examined using the PROCESS Model 1. Our findings showed that in depressed patients, childhood maltreatment had a significant positive impact on the severity of pain ratings. Moreover, anxious attachment influenced the relationship between childhood trauma and pain symptoms. Our study indicated that anxious attachment is not necessarily a negative outcome for depressed patients; moderate levels of anxious attachment alleviate childhood trauma-related pain symptoms in individuals with highly traumatic experiences. Understanding the traumatic experiences and attachment styles of depressed patients with pain complaints can help to develop intervention strategies.

Flexible and high-strength bioactive glass fiber membrane for bone regeneration with the aid of alkoxysilane sol spinnability.

In this research, the spinnability of bioactive glass (BG) precursor solution was supplied by alkoxysilane sol with appropriate molar ratio of H2O/silicon (R) to prepare bioactive glass fiber membrane (BFM) using electrospinning (ES) technique. Alkoxysilane could form a linear or chain-like colloidal aggregation in hydrolysis-polycondensation with R = 2 or so, thereby exhibiting good spinnability. Therefore, the role of polymer binders could be largely replaced. Due to the significant decrease of polymer binder, the defects within the fibers are largely reduced and degree of fiber densification was improved after calcination, leading to BFM drastically enhanced strength and flexibility. The effect of R and calcination temperature on mechanical performance were investigated in detail. The tensile strength could reach the highest value 2.31 MPa with R = 2 and calcination at 700 °C. In addition, under this preparation condition, the BFM also possessed good flexibility with bending rigidity 37.7 mN. Furthermore, the great performance of promoting cell proliferation and osteogenesis could be observed from in vitro cellular experiment. The BFM calcined at 750 °C exhibited the best promoting osteogenic differentiation ability. The rat skull defect model revealed BFM could perform well in osteogenesis in vivo.

Biomechanical Effects of Multi-segment Fixation on Lumbar Spine and Sacroiliac Joints: A Finite Element Analysis.

OBJECTIVE: Spine fixation surgery affects the biomechanical environment in the sacroiliac joint (SIJ), which may lead to the SIJ pain or degeneration after surgery. The purpose of this study is to determine the impact of the number and position of fixed segments on the SIJs and provide references for surgeons to plan fixation levels and enhance surgical outcomes. METHODS: The intact lumbar-pelvis finite element (FE) models and 11 fixation FE models with different number and position of fixed segments were developed based on CT images. A 400N follower load and 10° range of motion (ROM) of the spine were applied to the superior endplate of L1 to simulate the flexion, extension, bending and torsion motion after surgery. The peak stress on the SIJs, lumbar intervertebral discs, screws and rods were calculated to evaluate the biomechanical effects of fixation procedures. RESULTS: With the lowermost instrumented vertebra (LIV) of L5 or S1, the peak stress on SIJs increased with the number of fixed segments increasing. The flexion motion led to the greater von Mises stress on SIJ compared with other load conditions. Compared with the intact model, peak stress on all fixed intervertebral discs was reduced in the models with less than three fixed segments, and it increased in the models with more than three fixed segments. The stress on the SIJ was extremely high in the models with all segments from L1 to L5 fixed, including L1-L5, L1-S1 and L1-S2 fixation models. The stress on the segment adjacent to the fixed segments was significant higher compared to that in the intact model. The peak stress on rods and screws also increased with the number of fixed segments increasing in the flexion, extension and bending motion, and the bending and flexion motions led to the greater von Mises stress on SIJs. CONCLUSION: Short-term fixation (≤2 segments) did not increase the stress on the SIJs significantly, while long-term segment fixation (≥4 segments) led to greater stress on the SIJs especially when all the L1-L5 segments were fixed. Unfixed lumbar segments compensated the ROM loss of the fixed segments, and the preservation of lumbar spine mobility would reduce the risks of SIJ degeneration.

Association of intestinal anti-inflammatory drug target genes with psychiatric Disorders: A Mendelian randomization study.

INTRODUCTION: Psychiatric disorders present a substantial global public health burden with limited drug options. The gut-brain axis connects inflammatory bowel diseases and psychiatric disorders, which often have comorbidities. While some evidence hints at anti-inflammatory drugs aiding in treating psychiatric conditions, the specific effects of intestinal anti-inflammatory drugs remain unclear. OBJECTIVES: This study investigates the causal effect of intestinal anti-inflammatory drug targets on psychiatric disorders. We hypothesize that these drug targets may offer new insights into the treatment and prevention of such disorders. Additionally, we explore gut microbiota's mediating role between drug target genes and psychiatric disorders. METHODS: We performed two-sample Mendelian randomization (MR) using summary data from existing expression quantitative trait loci (eQTL) and protein QTL in the brain, along with public genome-wide association studies of disease. We also explored gut microbiota's mediating effect. The statistics encompassed six psychiatric disorders involving 9,725-500,199 individuals. Colocalization analysis enhanced the MR evidence. RESULTS: We uncovered a causal link between TPMT (a target of olsalazine) expression in the amygdala and bipolar disorder (BD) risk (odds ratio [OR] = 1.08; P = 4.29 × 10-4). This association was observed even when the sigmoid colon and whole blood eQTL were considered as exposures. Colocalization analysis revealed a shared genetic variant (rs11751561) between TPMT expression and BD, with a posterior probability of 61.6 %. Interestingly, this causal effect was influenced by a decrease in the gut microbiota abundance of the genus Roseburia (effect proportion = 10.05 %). Moreover, elevated ACAT1 expression was associated with higher obsessive-compulsive disorder risk (OR = 1.62; P = 3.64 × 10-4; posterior probability = 3.1 %). CONCLUSION: These findings provide novel targets for the treatment of psychiatric disorders, underscore the potential of repurposing olsalazine, and emphasize the importance of TPMT and ACAT1 in future drug development.

The Association of Redox Regulatory Drug Target Genes with Psychiatric Disorders: A Mendelian Randomization Study.

Redox regulatory drug (RRD) targets may be considered potential novel drug targets of psychosis due to the fact that the brain is highly susceptible to oxidative stress imbalance. The aim of the present study is to identify potential associations between RRD targets' perturbation and the risk of psychoses; to achieve this, Mendelian randomization analyses were conducted. The expression quantitative trait loci (eQTL) and protein QTL data were used to derive the genetic instrumental variables. We obtained the latest summary data of genome-wide association studies on seven psychoses as outcomes, including schizophrenia (SCZ), bipolar disorder (BD), major depressive disorder (MDD), attention-deficit/hyperactivity disorder, autism, obsessive-compulsive disorder and anorexia nervosa. In total, 95 unique targets were included in the eQTL panel, and 48 targets in the pQTL one. Genetic variations in the vitamin C target (OGFOD2, OR = 0.784, p = 2.14 × 10-7) and melatonin target (RORB, OR = 1.263, p = 8.80 × 10-9) were significantly related to the risk of SCZ. Genetic variation in the vitamin E (PRKCB, OR = 0.248, p = 1.24 × 10-5) target was related to an increased risk of BD. Genetic variation in the vitamin C target (P4HTM: cerebellum, OR = 1.071, p = 4.64 × 10-7; cerebellar hemisphere, OR = 1.092, p = 1.98 × 10-6) was related to an increased risk of MDD. Cognitive function mediated the effects on causal associations. In conclusion, this study provides supportive evidence for a causal association between RRD targets and risk of SCZ, BD or MDD, which were partially mediated by cognition.

Anti-Stress and Anti-ROS Effects of MnOx-Functionalized Thermosensitive Nanohydrogel Protect BMSCs for Intervertebral Disc Degeneration Repair.

Stem cell transplantation is proven to be a promising strategy for intervertebral disc degeneration (IDD) repair. However, replicative senescence of bone marrow-derived mesenchymal stem cells (BMSCs), shear damage during direct injection, mechanical stress, and the reactive oxygen species (ROS)-rich microenvironment in degenerative intervertebral discs (IVDs) cause significant cellular damage and limit the therapeutic efficacy. Here, an injectable manganese oxide (MnOx)-functionalized thermosensitive nanohydrogel is proposed for BMSC transplantation for IDD therapy. The MnOx-functionalized thermosensitive nanohydrogel not only successfully protects BMSCs from shear force and mechanical stress before and after injection, but also repairs the harsh high-ROS environment in degenerative IVDs, thus effectively increasing the viability of BMSCs and resident nucleus pulposus cells (NPCs). The MnOx-functionalized thermosensitive nanohydrogel provides mechanical protection for stem cells and helps to remove endogenous ROS, providing a promising stem cell delivery platform for the treatment of IDD.

Contribution of copy number variants on antipsychotic treatment response in Han Chinese patients with schizophrenia.

BACKGROUND: Response to antipsychotic drugs (APD) varies greatly among individuals and is affected by genetic factors. This study aims to demonstrate genome-wide associations between copy number variants (CNVs) and response to APD in patients with schizophrenia. METHODS: A total of 3030 patients of Han Chinese ethnicity randomly received APD (aripiprazole, olanzapine, quetiapine, risperidone, ziprasidone, haloperidol and perphenazine) treatment for six weeks. This study is a secondary data analysis. Percentage change on the Positive and Negative Syndrome Scale (PANSS) reduction was used to assess APD efficacy, and more than 50% change was considered as APD response. Associations between CNV burden, gene set, CNV loci and CNV break-point and APD efficacy were analysed. FINDINGS: Higher CNV losses burden decreased the odds of 6-week APD response (OR = 0.66 [0.44, 0.98]). CNV losses in synaptic pathway involved in neurotransmitters were associated with 2-week PANSS reduction rate. CNV involved in sialylation (1p31.1 losses) and cellular metabolism (19q13.32 gains) associated with 6-week PANSS reduction rate at genome-wide significant level. Additional 36 CNVs associated with PANSS factors improvement. The OR of protective CNVs for 6-week APD response was 3.10 (95% CI: 1.33-7.19) and risk CNVs was 8.47 (95% CI: 1.92-37.43). CNV interacted with genetic risk score on APD efficacy (Beta = -1.53, SE = 0.66, P = 0.021). The area under curve to differ 6-week APD response attained 80.45% (95% CI: 78.07%-82.82%). INTERPRETATION: Copy number variants contributed to poor APD efficacy and synaptic pathway involved in neurotransmitter was highlighted. FUNDING: National Natural Science Foundation of China, National Key R&D Program of China, China Postdoctoral Science Foundation.