Association between early-life mosquito repellents exposure and ADHD-like behaviours.

BACKGROUND: Limited research has explored the impact of mosquito repellents exposure during early life on ADHD symptoms. This study aimed to explore the associations of exposure to mosquito repellents from pregnancy to 3 years old and the prevalence of ADHD-like behaviours among children aged 3-9 years, and further identify the sensitive exposure period. METHODS: A cross-sectional study was conducted, including 12 275 children in Hefei City, China. Exposure was self-reported via primary caregivers. ADHD-like behaviours were measured by the Swanson, Nolan and Pelham, version IV scale (SNAP-IV), and Conners' Parent Rating Scale (CPRS). Cross-over analysis, binary logistic regression and linear regression were employed. RESULTS: After adjusting for confounding variables, early-life exposure to mosquito repellents was associated with a higher risk of ADHD-like behaviours (OR = 1.81, 95% CI = 1.49-2.19). By comparing the strength of the association for each subgroup, we found exposure during 1-3 years old was a sensitive period (OR = 1.89, 95% CI = 1.25-2.87) by the cross-over analysis. Furthermore, we found a dose-response relationship in which the likelihood of ADHD-like behaviours increased with children's early-life mosquito repellents exposure dose. CONCLUSIONS: Early-life exposure to mosquito repellents is linked with an elevated risk of ADHD-like behaviours in children, with a sensitive period identified during 1-3 years old.

Preparation and evaluation of decellularized epineurium as an anti-adhesive biofilm in peripheral nerve repair.

Following peripheral nerve anastomosis, the anastomotic site is prone to adhesions with surrounding tissues, consequently impacting the effectiveness of nerve repair. This study explores the development and efficacy of a decellularized epineurium as an anti-adhesive biofilm in peripheral nerve repair. Firstly, the entire epineurium was extracted from fresh porcine sciatic nerves, followed by a decellularization process. The decellularization efficiency was then thoroughly assessed. Subsequently, the decellularized epineurium underwent proteomic analysis to determine the remaining bioactive components. To ensure biosafety, the decellularized epineurium underwent cytotoxicity assays, hemolysis tests, cell affinity assays, and assessments of the immune response following subcutaneous implantation. Finally, the functionality of the biofilm was determined using a sciatic nerve transection and anastomosis model in rats. The result indicated that the decellularization process effectively removed cellular components from the epineurium while preserving a number of bioactive molecules, and this decellularized epineurium was effective in preventing adhesion while promoting nerve repairment and functional recovery. In conclusion, the decellularized epineurium represents a novel and promising anti-adhesion biofilm for enhancing surgical outcomes of peripheral nerve repair.

Improved cure rate of periprosthetic joint infection through targeted antibiotic therapy based on integrated pathogen diagnosis strategy.

Objectives: This study aimed to determine whether combined of pathogen detection strategies, including specimen acquisition, culture conditions, and molecular diagnostics, can improve treatment outcomes in patients with periprosthetic joint infections (PJI). Methods: This retrospective study included suspected PJI cases from three sequential stages at our institution: Stage A (July 2012 to June 2015), Stage B (July 2015 to June 2018), and Stage C (July 2018 to June 2021). Cases were categorized into PJI and aseptic failure (AF) groups based on European Bone and Joint Infection Society (EBJIS) criteria. Utilization of pathogen diagnostic strategies, pathogen detection rates, targeted antibiotic prescription rates, and treatment outcomes were analyzed and compared across the three stages. Results: A total of 165 PJI cases and 38 AF cases were included in this study. With the progressive implementation of the three optimization approaches across stages A, B and C, pathogen detection rates exhibited a gradual increase (χ2 = 8.282, P=0.016). Similarly, utilization of targeted antibiotic therapy increased stepwise from 57.1% in Stage A, to 82.3% in Stage B, and to 84% in Stage C (χ2 = 9.515, P=0.009). The 2-year infection control rate exceeded 90% in both stages B and C, surpassing stage A (71.4%) (χ2 = 8.317, P=0.011). Combined application of all three optimized protocols yielded the highest sensitivity of 91.21% for pathogen detection, while retaining higher specificity of 92.11%. Conclusion: The utilization of combined pathogen diagnostic strategies in PJI can increase pathogen detection rates, improve targeted antibiotic prescription, reduce the occurrence of antibiotic complications, and achieve better treatment outcomes.

Optical frequency multiplication using residual network with random forest regression.

In this work, we present a method for optical frequency multiplication utilizing a hybrid deep learning approach that integrates the Residual Network (ResNet) with the Random Forest Regression (RFR) algorithm. Three different frequency multiplication modulation schemes are adopted to illustrate the method, which can obtain suitable parameters for these schemes. Based on the parameters predicted by the algorithm, the 8-tupling, 12-tupling, and 16-tupling mm-wave signals are generated by numerical simulation. The simulation results show that for 8-tupling frequency multiplication, an OSSR (optical sideband suppression ratio) is 30.73 dB and an RFSSR (radio frequency spurious suppression ratio) of 80 GHz is 42.29 dB. For 12-tupling frequency multiplication, the OSSR is 30.09 dB, and the RFSSR of the 120 GHz mm wave is 36.21 dB. For generating 16-tupling frequency mm-wave, an OSSR of 29.86 dB and an RFSSR of 34.52 dB are obtained. In addition, the impact of amplitude fluctuation and bias voltage drift on the quality of mm-wave signals is also studied.

Fabrication of bulk superhydrophobic wood by grafting porous poly(divinylbenzene) to wood structure using isocyanatoethyl methacrylate.

Superhydrophobic treatment of wood can effectively reduce the interaction between wood and moisture, avoiding deformation, cracking, mould, and other defects caused by water absorption, which can extend the service life of wood and broaden the application field. Currently, the poor abrasion resistance of superhydrophobic wood is a crucial problem limiting its widespread application, and the preparation of superhydrophobic wood with robustness, abrasion resistance, and chemical resistance remains a huge challenge. In this work, robust bulk superhydrophobic wood with excellent abrasion resistance and chemical durability was fabricated by synthesizing porous poly(divinylbenzene) in wood cell cavities using graft copolymerization and solvothermal methods. The contact angles and rolling angles on the superhydrophobic wood surface were approximately 156° and 3°, respectively. Superhydrophobicity was carried through the entire structure of the wood. Even after severe damage by abrasion and sawing, as well as tests with organic solvents and harsh environments, the superhydrophobic properties of wood remained stable. Meanwhile, the superhydrophobic wood exhibited great self-cleaning and antifouling properties. In addition, the water uptake and dimensional stability of the wood were significantly improved. This work developed a simple, efficient, and durable strategy for the fabrication of superhydrophobic wood with robustness, abrasion resistance, and chemical resistance, which was expected to be applied to the wood industry to achieve the high-value applications of wood products and extend their service life.

Associations of phthalates with accelerated aging and the mitigating role of physical activity.

Phthalates are positioned as potential risk factors for health-related diseases. However, the effects of exposure to phthalates on accelerated aging and the potential modifications of physical activity remain unclear. A total of 2317 participants containing complete study-related information from the National Health and Nutrition Examination Survey 2007-2010 were included in the current study. We used two indicators, the Klemera-Doubal method biological age acceleration (BioAgeAccel) and phenotypic age acceleration (PhenoAgeAccel), to assess the accelerated aging status of the subjects. Multiple linear regression (single pollutant models), weighted quantile sum (WQS) regression, Quantile g-computation, and Bayesian kernel machine regression (BKMR) models were utilized to explore the associations between urinary phthalate metabolites and accelerated aging. Three groups of physical activity with different intensities were used to evaluate the modifying effects on the above associations. Results indicated that most phthalate metabolites were significantly associated with BioAgeAccel and PhenoAgeAccel, with effect values (ß) ranging from 0.16 to 0.21 and 0.16-0.37, respectively. The WQS indices were positively associated with BioAgeAccel (0.33, 95% CI: 0.11, 0.54) and PhenoAgeAccel (0.50, 95% CI: 0.19, 0.82). Quantile g-computation indicated that phthalate mixtures were associated with accelerated aging, with effect values of 0.15 (95% CI: 0.02, 0.28) for BioAgeAccel and 0.39 (95% CI: 0.12, 0.67) for PhenoAgeAccel respectively. The BKMR models indicated a significant positive association between the concentrations of urinary phthalate mixtures with the two indicators. In addition, we found that most phthalate metabolites showed the strongest effects on accelerated aging in the no physical activity group and that the effects decreased gradually with increasing levels of physical activity (P < 0.05 for trend). Similar results were also observed in the mixed exposure models (WQS and Quantile g-computation). This study indicates that phthalates exposure is associated with accelerated aging, while physical activity may be a crucial barrier against phthalates exposure-related aging.

Disruption of pulmonary microvascular endothelial barrier by dysregulated claudin-8 and claudin-4: uncovered mechanisms in porcine reproductive and respiratory syndrome virus infection.

The pulmonary endothelium is a dynamic and metabolically active monolayer of endothelial cells. Dysfunction of the pulmonary endothelial barrier plays a crucial role in the acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), frequently observed in the context of viral pneumonia. Dysregulation of tight junction proteins can lead to the disruption of the endothelial barrier and subsequent leakage. Here, the highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) served as an ideal model for studying ALI and ARDS. The alveolar lavage fluid of pigs infected with HP-PRRSV, and the supernatant of HP-PRRSV infected pulmonary alveolar macrophages were respectively collected to treat the pulmonary microvascular endothelial cells (PMVECs) in Transwell culture system to explore the mechanism of pulmonary microvascular endothelial barrier leakage caused by viral infection. Cytokine screening, addition and blocking experiments revealed that proinflammatory cytokines IL-1ß and TNF-α, secreted by HP-PRRSV-infected macrophages, disrupt the pulmonary microvascular endothelial barrier by downregulating claudin-8 and upregulating claudin-4 synergistically. Additionally, three transcription factors interleukin enhancer binding factor 2 (ILF2), general transcription factor III C subunit 2 (GTF3C2), and thyroid hormone receptor-associated protein 3 (THRAP3), were identified to accumulate in the nucleus of PMVECs, regulating the transcription of claudin-8 and claudin-4. Meanwhile, the upregulation of ssc-miR-185 was found to suppress claudin-8 expression via post-transcriptional inhibition. This study not only reveals the molecular mechanisms by which HP-PRRSV infection causes endothelial barrier leakage in acute lung injury, but also provides novel insights into the function and regulation of tight junctions in vascular homeostasis.

Sex differences and dietary patterns in the association of air pollutants and hypertension.

BACKGROUND: Hypertension is one of the major public health problems in China. Limited evidence exists regarding sex differences in the association between hypertension and air pollutants, as well as the impact of dietary factors on the relationship between air pollutants and hypertension. The aim of this study was to investigate the sex-specific effects of dietary patterns on the association between fine particulate matter (PM2.5), ozone(O3) and hypertension in adults residing in Jiangsu Province of China. METHODS: A total of 3189 adults from the 2015 China Adult Chronic Disease and Nutrition Surveillance in Jiangsu Province were included in this study. PM2.5 and O3 concentrations were estimated using satellite space-time models and assigned to each participant. Dietary patterns were determined by reduced rank regression (RRR), and multivariate logistic regression was used to assess the associations of the obtained dietary patterns with air pollutants and hypertension risk. RESULTS: After adjusting for confounding variables, we found that males were more sensitive to long-term exposure to PM2.5 (Odds ratio (OR) = 1.42 95%CI:1.08,1.87), and females were more sensitive to long-term exposure to O3 (OR = 1.61 95%CI:1.15,2.23). Traditional southern pattern identified through RRR exhibited a protective effect against hypertension in males (OR = 0.73 95%CI: 0.56,1.00). The results of the interaction between dietary pattern score and PM2.5 revealed that adherence to traditional southern pattern was significantly associated with a decreased risk of hypertension in males (P < 0.05), while no significant association was observed among females. CONCLUSIONS: Our findings suggested that sex differences existed in the association between dietary patterns, air pollutants and hypertension. Furthermore, we found that adherence to traditional southern pattern may mitigate the risk of long-term PM2.5 exposure-induced hypertension in males.

Detection of Cadmium(II) in Aquatic Products Using a Rolling-Circle Amplification-Coupled Ratio Fluorescent Probe Based on an Aptamer-Peptide Conjugate.

The existing aptamers for cadmium (Cd2+), the common toxic heavy metal contaminant in food, cannot meet the requirements for detecting Cd2+ in rapid detection methods. In previous work, we found that coupling aptamer-peptide conjugates (APCs) with peptides and aptamers can provide a less disruptive method with a significantly improved affinity. Moreover, we found that the spatial conformation of aptamers and peptides is crucial for obtaining proper affinity in APC. Therefore, we describe a simple design strategy to obtain a series of APCs with different affinities by designing peptide orientations (N-terminal, C-terminal). The best affinity was found for APC(C1-N) with a binding constant (Ka) of 2.23 × 106 M-1, indicating that the APC(C1-N) affinity was significantly increased by 829.17% over aptamer. Finally, a rolling-circle amplification (RCA)-coupled ratio fluorescence-based biosensor for Cd2+ detection was established with a detection limit of 0.0036 nM, which has great potential for practical aquatic product detection.

Association between caregiver-child interaction and autistic-like behaviors at around three years of age.

BACKGROUND: The prevalence of autistic-like behaviors is increasing worldwide, both in developed and developing countries. With a high disease burden and complex developmental causes, there has been much interest in the etiology of the disease, and there is a lack of evidence on the relationship between caregiver-child interaction and autistic-like behaviors. AIM/OBJECTIVE: This study investigated the association between caregiver-child interaction and children's autistic-like behaviors during early childhood. METHOD: The subjects of this study were 171 kindergartens selected from the Longhua Child Cohort Study (LCCS), and a total of 40,237 children around the age of three were included. Sociodemographic characteristics, family income, and frequency of interaction between caregivers and children were all filled in by the child's primary caregiver, and the adapted Chinese Autism Behavior Checklist was used to assess children's autism-like behaviors. Tobit Regression and ancovariance analysis (ANCOVA) were used to measure the relationship between caregiver-child interactions (family and social activities) and autism-like behaviors, with a two-tailed p value of <0.05 being significant. RESULTS: Tobit regression analyses found that in the 0-1 year age group, different frequencies of singing activities by caregivers with children (<3 times per week, 3-6 times per week, 6 times or more per week) were significantly negatively associated with autistic-like behaviors in a dose-response manner (B values of -0.323, -0.381, -0.544, all p < 0.0001); in the 1-3 year age group, different frequencies of reading interactions by caregivers with children (<3 times per week, 3-6 times per week, 6 times or more per week) were also significantly negatively associated with autistic-like behaviors in a dose-response manner (B values of -0.388, -0.632, -0.956, all p < 0.0001), and similar associations were found in singing and chatting interactions. CONCLUSIONS: Our findings suggest that higher frequencies of early caregiver-child interactions are associated with lower levers of autistic-like behaviors in children around the age of three years.

Association between increased BMI and cognitive function in first-episode drug-naïve male schizophrenia.

Objective: Although the adverse effects of obesity in schizophrenia are documented, there is limited research exists on the implications for untreated initial schizophrenia. Our investigation aimed to explore the connections between BMI and cognitive function in first-episode drug-naïve (FEDN)schizophrenia. Methods: We enrolled 143 FEDN schizophrenia patients, and collected data on their body mass index, fasting blood glucose and lipid levels. Cognitive function was measured with the MATRICS Consensus Cognitive Battery (MCCB). Using correlation and regression analysis to assess the relationship between BMI and cognitive performance. Results: The prevalence rate of overweight plus obesity in FEDN schizophrenia patients was 33.57%. Patients with FEDN schizophrenia exhibited extensive cognitive impairment, and those who were overweight/obesity demonstrated more severe impairments in working memory and visual learning when compared to normal/under weight counterparts. Correlation analysis indicated a negative association between working memory and BMI and TG, as well as a link between visual learning and BMI and LDL-C. Multiple linear regression analysis revealed that a higher BMI predicted a decrease in working memory in FEDN schizophrenia patients. Conclusion: Our results indicate that the rate of overweight plus obesity is high in FEDN schizophrenia patients, and there is an association between BMI and cognitive function in schizophrenia, particularly in relation to working memory.

The GDNF-gel/HA-Mg conduit promotes the repair of peripheral nerve defects by regulating PPAR-γ/RhoA/ROCK signaling pathway.

Magnesium (Mg)-based conduits have gained more attention in repairing peripheral nerve defects. However, they are limited due to poor corrosion resistance and rapid degradation rate. To tackle this issue, glial cell line-derived neurotrophic factor (GDNF)- Gelatin methacryloyl (Gel)/hydroxylapatite (HA)-Mg nerve conduit was developed and implanted in sciatic nerve defect model in Sprague-Dawley (SD) rats. The sciatic functional index measurement showed that the GDNF-Gel/HA-Mg nerve conduit effectively promoted the recovery of sciatic nerve function. The pathological examination results showed that there were more regenerated nerve tissues in GDNF-Gel/HA-Mg group, with a higher number of regenerating axons, and the thickness of the myelin sheath was significantly larger than that of control group (NC group). Immunofluorescence results revealed that the GDNF-Gel/HA-Mg conduit significantly promoted the expression of genes associated with nerve repair. RNA-seq and molecular test results indicated that GDNF-Gel/HA-Mg might be involved in the repair of peripheral nerve defects by regulating PPAR-γ/RhoA/ROCK signaling pathway. Biological sciences; Neuroscience; Molecular neuroscience; Techniques in neuroscience.

Plasma Apo-E mediated corticospinal tract abnormalities and suicidality in patients with major depressive disorder.

This study aims to explore the link between Apo-E, brain white matter, and suicide in patients with major depressive disorder (MDD) to investigate the potential neuroimmune mechanisms of Apo-E that may lead to suicide. Thirty-nine patients with MDD (22 patients with suicidality) and 57 age, gender, and education-matched healthy controls participated in this study, provided plasma Apo-E samples, and underwent diffusion tensor imaging scans. Plasma Apo-E levels and white matter microstructure were analyzed among the MDD with suicidality, MDD without suicidality, and HC groups using analysis of variance with post hoc Bonferroni correction and tract-based spatial statistics (TBSS) with threshold-free cluster enhancement correction. Mediation analysis investigated the relationship between Apo-E, brain white matter, and suicidality in MDD. The MDD with suicidality subgroup had higher depressive and suicide scores, longer disease course, and lower plasma Apo-E levels than MDD without suicidality. TBSS revealed that the MDD non-suicide subgroup showed significantly increased mean diffusivity in the left corticospinal tract and body of the left corpus callosum, as well as increased axial diffusivity in the left anterior corona radiata and the right posterior thalamic radiation compared to the suicidal MDD group. The main finding was that the increased MD of the left corticospinal tract contributed to the elevated suicide score, with Apo-E mediating the effect. Preliminary result that Apo-E's mediating role between the left corticospinal tract and the suicide factor suggests the neuroimmune mechanism of suicide in MDD. The study was registered on ClinicalTrials.gov (NCT03790085).

Pathway from childhood trauma to nonsuicidal self-injury in adolescents with major depressive disorder: the chain-mediated role of psychological resilience and depressive severity.

This study aimed to explore the pathway from childhood trauma to nonsuicidal self-injury (NSSI) in adolescents with major depressive disorder (MDD) and to examine the chain-mediating role of psychological resilience and depressive symptoms in this pathway. A total of 391 adolescents with MDD were recruited in the present study. The Chinese version of the Childhood Trauma Questionnaire-Short Form (CTQ-SF), the Chinese version of the Symptoms Check List-90 (SCL-90), the Chinese version of the Conner-Davidson Resilience Scale (CD-RISC), and the Ottawa Self-Injury Inventory Chinese Revised Edition (OSIC) were used to evaluate childhood trauma, depressive symptoms, psychological resilience and NSSI, respectively. Our results showed that 60.87% of adolescents with MDD had NSSI in the past month. Childhood trauma frequency was negatively correlated with psychological resilience but positively correlated with depressive symptoms and NSSI severity in adolescents with MDD. The stepwise logistic regression analysis identified that age, childhood trauma and depressive symptoms could independently predict the occurrence of NSSI, and the three-step hierarchical regression showed that childhood trauma, psychological resilience and depressive symptoms were all significantly associated with NSSI frequency in adolescents with MDD. Furthermore, the chain-mediation analysis revealed that psychological resilience and depression serially mediated the relationship between childhood trauma and NSSI in adolescents with MDD. Interventions targeted at improving resilience and depression may mitigate the impact of childhood trauma severity on NSSI risk in adolescents with MDD.

Systemic inflammatory biomarkers in Schizophrenia are changed by ECT administration and related to the treatment efficacy.

Immune inflammation has long been implicated in the pathogenesis of schizophrenia. Despite as a rapid and effective physical therapy, the role of immune inflammation in electroconvulsive therapy (ECT) for schizophrenia remains elusive. The neutrophils to lymphocytes (NLR), platelets to monocytes (PLR) and monocytes to lymphocytes (MLR) are inexpensive and accessible biomarkers of systemic inflammation. In this study, 70 schizophrenia patients and 70 age- and sex-matched healthy controls were recruited. The systemic inflammatory biomarkers were measured before and after ECT. Our results indicated schizophrenia had significantly higher peripheral NLR, PLR and MLR compared to health controls at baseline, while lymphocytes did not differ. After 6 ECT, the psychiatric symptoms were significantly improved, as demonstrated by the Positive and Negative Syndrome Scale (PANSS). However, there was a decline in cognitive function scores, as indicated by the Mini-Mental State Examination (MMSE). Notably, the neutrophils and NLR were significantly reduced following ECT. Although lymphocytes remained unchanged following ECT, responders had significantly higher lymphocytes compared to non-responders. Moreover, the linear regression analyses revealed that higher lymphocytes served as a predictor of larger improvement in positive symptom following ECT. Overall, our findings further highlighted the presence of systemic inflammation in schizophrenia patients, and that ECT may exert a therapeutic effect in part by attenuating systemic inflammation. Further research may therefore lead to new treatment strategies for schizophrenia targeting the immune system.

Circular RNA-circPan3 attenuates cardiac hypertrophy via miR-320-3p/HSP20 axis.

BACKGROUND: Circular RNAs are enriched in cardiac tissue and play important roles in the pathogenesis of heart diseases. In this study, we aimed to investigate the regulatory mechanism of a conserved heart-enriched circRNA, circPan3, in cardiac hypertrophy. METHODS: Cardiac hypertrophy was induced by isoproterenol. The progression of cardiomyocyte hypertrophy was assessed by sarcomere organization staining, cell surface area measurement, and expression levels of cardiac hypertrophy markers. RNA interactions were detected by RNA pull-down assays, and methylated RNA immunoprecipitation was used to detect m6A level. RESULTS: The expression of circPan3 was downregulated in an isoproterenol-induced cardiac hypertrophy model. Forced expression of circPan3 attenuated cardiomyocyte hypertrophy, while inhibition of circPan3 aggravated cardiomyocyte hypertrophy. Mechanistically, circPan3 was an endogenous sponge of miR-320-3p without affecting miR-320-3p levels. It elevated the expression of HSP20 by endogenously interacting with miR-320-3p. In addition, circPan3 was N6-methylated. Stimulation by isoproterenol downregulated the m6A eraser ALKBH5, resulting in N6-methylation and destabilization of circPan3. CONCLUSIONS: Our research is the first to report that circPan3 has an antihypertrophic effect in cardiomyocytes and revealed a novel circPan3-modulated signalling pathway involved in cardiac hypertrophy. CircPan3 inhibits cardiac hypertrophy by targeting the miR-320-3p/HSP20 axis and is regulated by ALKBH5-mediated N6-methylation. This pathway could provide potential therapeutic targets for cardiac hypertrophy.

Fatty acid binding protein 4 (FABP4) induces chondrocyte degeneration via activation of the NF-κb signaling pathway.

The pathogenesis of osteoarthritis (OA) is still unclear. Fatty acid binding protein 4 (FABP4), a novel adipokine, has been found to play a role in OA. This study aimed to explore the role of NF-κB in FABP4-induced OA. In the in vivo study, four pairs of 12-week-old male FABP4 knockout (KO) and wild-type (WT) mice were included. The activation of NF-κB was assessed. In parallel, 24 6-week-old male C57/Bl6 mice were fed a high-fat diet (HFD) and randomly allocated to four groups: daily oral gavage with (1) PBS solution; (2) QNZ (NF-κB-specific inhibitor, 1 mg/kg/d); (3) BMS309403 (FABP4-specific inhibitor, 30 mg/kg/d); and (4) BMS309403 (30 mg/kg/d) + QNZ (1 mg/kg/d). The diet and treatment were sustained for 4 months. The knee joints were obtained to assess cartilage degradation, NF-κB activation, and subchondral bone sclerosis. In the in vitro study, a mouse chondrogenic cell line (ATDC5) was cultured. FABP4 was supplemented to stimulate chondrocytes, and the activation of NF-κB was investigated. In parallel, QNZ and NF-κB-specific siRNA were used to inhibit NF-κB. In vivo, the FABP4 WT mice had more significant NF-κB activation than the KO mice. Dual inhibition of FABP4 and NF-κB alleviated knee OA in mice. FABP4 has no significant effect on the activation of the JNK signaling pathway. In vitro, FABP4 directly activated NF-κB in chondrocytes. The use of QNZ and NF-κB-siRNA significantly alleviated the expression of catabolic markers of chondrocytes induced by FABP4. FABP4 induces chondrocyte degeneration by activating the NF-κB pathway.

TRPV1+ neurons alter Staphylococcus aureus skin infection outcomes by affecting macrophage polarization and neutrophil recruitment.

BACKGROUND: The interaction between the nervous system and the immune system can affect the outcome of a bacterial infection. Staphylococcus aureus skin infection is a common infectious disease, and elucidating the relationship between the nervous system and immune system may help to improve treatment strategies. RESULTS: In this study, we found that the local release of calcitonin gene-related peptide (CGRP) increased during S. aureus skin infection, and S. aureus could promote the release of CGRP from transient receptor potential cation channel subfamily V member 1 (TRPV1+) neurons in vitro. The existence of TRPV1+ neurons inhibited the recruitment of neutrophils to the infected region and regulated the polarization of macrophages toward M2 while inhibiting polarization toward M1. This reduces the level of inflammation in the infected area, which aggravates the local infection. Furthermore, this study demonstrates that TRPV1 may be a target for the treatment of S. aureus skin infections and that botulinum neurotoxin A (BoNT/A) and BIBN4096 may reverse the inhibited inflammatory effect of CGRP, making them potential therapeutics for the treatment of skin infection in S. aureus. CONCLUSIONS: In S. aureus skin infection, TRPV1+ neurons inhibit neutrophil recruitment and regulate macrophage polarization by releasing CGRP. BoNT/A and BIBN4096 may be potential therapeutic agents for S. aureus skin infection.

Altered brain functional networks in schizophrenia with persistent negative symptoms: an activation likelihood estimation meta-analysis.

Objective: To investigate brain structural and functional characteristics of three brain functional networks including default mode network (DMN), central executive network (CEN), and salience network (SN) in persistent negative symptoms (PNS) patients. Methods: We performed an activation likelihood estimation (ALE) meta-analysis of functional connectivity (FC) studies and voxel-based morphometry (VBM) studies to detect specific structural and functional alterations of brain networks between PNS patients and healthy controls. Results: Seventeen VBM studies and twenty FC studies were included. In the DMN, PNS patients showed decreased gray matter in the bilateral medial frontal gyrus and left anterior cingulate gyrus and a significant reduction of FC in the right precuneus. Also, PNS patients had a decrease of gray matter in the left inferior parietal lobules and medial frontal gyrus, and a significant reduction of FC in the bilateral superior frontal gyrus in the CEN. In comparison with healthy controls, PNS patients exhibited reduced gray matter in the bilateral insula, anterior cingulate gyrus, left precentral gyrus and right claustrum and lower FC in these brain areas in the SN, including the left insula, claustrum, inferior frontal gyrus and extra-nuclear. Conclusion: This meta-analysis reveals brain structural and functional imaging alterations in the three networks and the interaction among these networks in PNS patients, which provides neuroscientific evidence for more personalized treatment.Systematic Review RegistrationThe PROSPERO (https://www.crd.york.ac.uk/PROSPERO/, registration number: CRD42022335962).

Epidemiological characteristics and temporal-spatial clustering analysis on human brucellosis in Jiangsu Province, 2006-2021.

The marked increase in the incidence rate of brucellosis is a serious public health concern in Jiangsu Province. However, its temporal and spatial distribution has not been studied in depth. The main purpose of this study is to depict the demographic, temporal and spatial distribution patterns and clustering characteristics of brucellosis cases in Jiangsu Province, China, from 2006 to 2021 to develop and implement effective scientific prevention and control strategies. Data for human brucellosis cases in Jiangsu Province from 2006 to 2021 were obtained from the Nationwide Notifiable Infectious Diseases Reporting Information System (NIDRIS). Spatial autocorrelation analysis and temporal-spatial scan statistics were used to identify potential changes in the spatial and temporal distributions of human brucellosis in Jiangsu Province. During the years 2006-2021, 1347 brucellosis cases were reported in Jiangsu Province, with an average annual incidence rate of 0.1036 per 100,000 individuals. Middle-aged and elderly individuals (aged 40-69 years) were the main infected populations, accounting for 69.72% (939/1347) of all reported cases. The incidence of brucellosis in Jiangsu showed a long-term increasing trend and displayed pronounced seasonal variations, with the peak occurring between April and June annually. The incidence gradually expanded from the northern and southern areas to the central areas between 2006 and 2021. Global spatial autocorrelation analysis demonstrated a positive correlation in the incidence of brucellosis between 2008 and 2012-2021. Temporal-spatial clustering analysis showed that the primary cluster was detected in the northern, highly endemic regions of Jiangsu, and the three secondary clusters were in areas where there had been outbreaks of brucellosis. Human brucellosis remains a serious public health issue in Jiangsu Province. Northern and southern Jiangsu regions, with high rates of brucellosis, may require special plans and measures to monitor and control the disease. Additionally, the capacity to respond to outbreaks in high-incidence areas should be improved to prevent further brucellosis outbreaks.