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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.

Abstract 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 (P FWE = 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 (P FDR

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.

Summary: 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.

Abstract 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. Graphical Abstract

Abstract A growing body of research suggests that social or physical activity can affect the risk of Major depressive disorder (MDD). However, the bidirectional relationship between them remains to be clarified further, especially between inactivity and MDD. Here, we performed a two-sample Mendelian Randomization analysis using genetic variants associated with social/physical activities and MDD, and assessed the mediating effect of obesity-related measures and brain imaging phenotypes. The dataset on MDD, social activities, and physical activities included 500,199; 461,369; 460,376 individuals, respectively. Information regarding body mass index (BMI), body fat percentage (BFP), IDPs for 454,633; 461,460; 8,428 participants, respectively. We identified bidirectional causal relationships between sport clubs or gyms, strenuous sports, heavy do-it-youself, other exercises and MDD. We also observed that leisure/social inactivity (odds ratio [OR] = 1.64; P = 5.14 × 10−5) or physical inactivity (OR = 3.67; P = 1.99 × 10−5) caused an increased risk of MDD, which were partially mediated by BMI or BFP and masked by the weighted-mean orientation dispersion index of left acoustic radiation or volume of right caudate. Furthermore, we discovered that MDD increased the risk of leisure/social inactivity (OR = 1.03; P = 9.89 × 10−4) or physical inactivity (OR = 1.01; P = 7.96 × 10−4). In conclusions, we found that social/physical activities reduced the risk of MDD, while MDD in turn hindered social/physical activities. Inactivity may increase the risk of MDD, which was mediated or masked by brain imaging phenotypes. These results help to understand the manifestations of MDD and provide evidence and direction for the advancement of intervention and prevention.

Stem cell transplantation has been proved a promising therapeutic instrument in intervertebral disc degeneration (IVDD). However, the elevation of oxidative stress in the degenerated region impairs the efficiency of mesenchymal stem cells (BMSCs) transplantation treatment via exaggeration of mitochondrial ROS and promotion of BMSCs apoptosis. Herein, we applied an emulsion-confined assembly method to encapsulate Coenzyme Q10 (Co-Q10), a promising hydrophobic antioxidant which targets mitochondria ROS, into the lecithin micelles, which renders the insoluble Co-Q10 dispersible in water as stable colloids. These micelles are injectable, which displayed efficient ability to facilitate Co-Q10 to get into BMSCs in vitro, and exhibited prolonged release of Co-Q10 in intervertebral disc tissue of animal models. Compared to mere use of Co-Q10, the Co-Q10 loaded micelle possessed better bioactivities, which elevated the viability, restored mitochondrial structure as well as function, and enhanced production of ECM components in rat BMSCs. Moreover, it is demonstrated that the injection of this micelle with BMSCs retained disc height and alleviated IVDD in a rat needle puncture model. Therefore, these Co-Q10 loaded micelles play a protective role in cell survival and differentiation through antagonizing mitochondrial ROS, and might be a potential therapeutic agent for IVDD.

Objectives Bags such as handbags, shoulder bags, and backpacks are commonly used. However, it is difficult to assess the biomechanical effects of bag‐carrying styles on the lumbar spine and paraspinal muscles using traditional methods. This study aimed to evaluate the biomechanical effects of bag‐carrying styles on the lumbar spine. Methods We developed a hybrid model that combined a finite element (FE) model of the lumbar spine and musculoskeletal models of three bag‐carrying styles. The image data was collected from a 26‐years‐old, 176 cm and 70 kg volunteer. OpenSim and ABAQUS were used to do the musculoskeletal analysis and finite analysis. Paraspinal muscle force, intervertebral compressive force (ICF), and intervertebral shear force (ISF) on L1 were calculated and loaded into the FE model to assess the stress distribution on the lumbar spine. Results Different paraspinal muscle activation occurred in the three bag‐carrying models. The increase in the ICF generated by all three bags was greater than the bags' weights. The handbag produced greater muscle force, ICF, ISF, and peak stress on the nucleus pulposus than the backpack and shoulder bag of the same weight. Peak stress on the intervertebral discs in the backpack model and the L1–L4 segments of the shoulder bag model increased linearly with bag weight, and increased exponentially with bag weight in the handbag model. Conclusion Unbalanced bag‐carrying styles (shoulder bags and handbags) led to greater muscle force, which generated greater ICF, ISF, and peak stress on the lumbar spine. The backpack produced the least burden on the lumbar spine and paraspinal muscles. Heavy handbags should be used carefully in daily life.

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.

Walnuts (Juglans regia L.) are a major food crop in Beijing. Recently, walnut anthracnose has become a serious problem in walnut plantations of Beijing, and the diversity of pathogens that cause this disease is poorly understood, making targeted treatment difficult. This study investigated incidences of walnut anthracnose in seven districts of Beijing (Changping, Fangshan, Haidian, Huairou, Mentougou, Miyun and Pinggu). A total of 377 isolates of Colletotrichum spp. were obtained from walnut anthracnose infected leaves and fruits. Morphological observation and multigene phylogenetic analysis of the genes ACT, CAL, CHS-1, GAPDH, ITS and TUB2 revealed that the isolates consisted of six species, C. aenigma, C. fructicola, C. gloeosporioides, C. siamense, C. liaoningense and C. sojae. Among these, C. gloeosporioides was the dominant species, and, for the first time, C. liaoningense and C. sojae were found to cause anthracnose in walnuts. Sensitivity tests showed that prochloraz and SYP-14288 had the strongest inhibitory effect on mycelial growth. These findings have clarified the species that cause walnut anthracnose in these seven districts of Beijing, which provides a scientific basis for diagnosis and control of walnut anthracnose.