Aberrant brain functional connectivity mediates the effects of negative symptoms on cognitive function in schizophrenia: A structural equation model.

BACKGROUND: Schizophrenia is a severe psychiatric disorder, characterized by positive symptoms, negative symptoms, and cognitive deficits. Elucidating the mechanism of negative symptom and cognitive deficits could contribute to the treatment and prognosis of schizophrenia. We hypothesized that abnormal functional connectivity would be involved in the indirect effects of negative symptoms on cognitive function. METHODS: A total of 150 schizophrenia male patients and 108 healthy controls matched for age, education and gender were enrolled in the study. The scores of Brief Negative Symptom Scale were divided into two factors: motivation and pleasure deficits (MAP) and diminished expression (EXP). Subsequently, a series of classic neurocognitive tests were used to evaluate cognitive functions. Resting-state fMRI data was collected from all participants. The Anatomical Automatic Labeling template was employed to establish regions of interest, thereby constructing the functional connectivity network across the entire brain. Eventually, scores of patients' negative symptoms scale, cognitive function, and strengths of abnormal functional connectivity were incorporated into a structural equation model to explore the interactions among variables. RESULTS: MAP exhibited a distinctly and significantly negative impact on cognitive function. The functional connectivity between the left insula and left precuneus, along with that between the left precuneus and right angular gyrus, collectively served as intermediaries, contributing to the indirect effects of MAP and EXP on cognitive function. CONCLUSIONS: Our findings demonstrated the moderating role of aberrant brain functional connectivity between negative symptoms and cognitive function, providing clues about the neural correlates of negative symptoms and cognitive deficits in schizophrenia.

Oxidative modification of miR-30c promotes cardiac fibroblast proliferation via CDKN2C mismatch.

The response of cardiac fibroblast proliferation to detrimental stimuli is one of the main pathological factors causing heart remodeling. Reactive oxygen species (ROS) mediate the proliferation of cardiac fibroblasts. However, the exact molecular mechanism remains unclear. In vivo, we examined the oxidative modification of miRNAs with miRNA immunoprecipitation with O8G in animal models of cardiac fibrosis induced by Ang II injection or ischemia‒reperfusion injury. Furthermore, in vitro, we constructed oxidation-modified miR-30c and investigated its effects on the proliferation of cardiac fibroblasts. Additionally, luciferase reporter assays were used to identify the target of oxidized miR-30c. We found that miR-30c oxidation was modified by Ang II and PDGF treatment and mediated by excess ROS. We demonstrated that oxidative modification of G to O8G occurred at positions 4 and 5 of the 5' end of miR-30c (4,5-oxo-miR-30c), and this modification promoted cardiac fibroblast proliferation. Furthermore, CDKN2C is a negative regulator of cardiac fibroblast proliferation. 4,5-oxo-miR-30c misrecognizes CDKN2C mRNA, resulting in a reduction in protein expression. Oxidized miR-30c promotes cardiac fibroblast proliferation by mismatch mRNA of CDKN2C.

Alloferon Mitigates LPS-Induced Endometritis by Attenuating the NLRP3/CASP1/IL-1ß/IL-18 Signaling Cascade.

Endometritis is an inflammatory reaction of the uterine lining that can lead to infertility. Alloferon, a linear non-glycosylated oligopeptide, has been recognized for its potent anti-inflammatory and immunomodulatory effects. In light of these attributes, this study aims to explore the potential therapeutic effects of alloferon in alleviating endometrial inflammation induced by lipopolysaccharide (LPS), while elucidating the underlying protective mechanisms. Two conditions representing pre- and post-menopause states were simulated using an ovariectomized (Ovx) murine model. The findings underscore alloferon's remarkable capacity to alleviate cardinal signs of endometritis, including redness, swelling, and congestion, while concurrently restoring the structural integrity of the endometrial tissue. Moreover, alloferon effectively modulates the expression of key inflammatory mediators, such as nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3), cysteine aspartate-specific protease 1 (CASP1), interleukin-1ß (IL-1ß), and interleukin-18 (IL-18). In vitro experiments were conducted to further corroborate and validate these findings. In conclusion, alloferon shows promising potential in mitigating LPS-induced inflammation by attenuating the NLRP3/CASP1/IL-1ß/IL-18 signaling cascade.

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.

The effects of childhood trauma on nonsuicidal self-injury and depressive severity among adolescents with major depressive disorder: The different mediating roles of positive and negative coping styles.

OBJECTIVE: We aimed to examine whether positive and negative coping styles mediated the influences of childhood trauma on NSSI or depressive severity in adolescents with major depressive disorder (MDD). METHODS: The Children's Depression Inventory (CDI), the Ottawa Self-Injury Inventory Chinese Revised Edition (OSIC), the short-form Childhood Trauma Questionnaire (CTQ-SF), and the Simplified Coping Style Questionnaire (SCSQ) were evaluated in 313 adolescents with MDD. RESULTS: MDD adolescents with NSSI had higher CTQ-SF total score, emotional and sexual abuse subscale scores, but lower CDI total and subscale scores compared to the patients without NSSI. The multiple linear regression analysis revealed that emotional abuse (ß = 0.075, 95 % CI: 0.042-0.107) and ineffectiveness (ß = -0.084, 95 % CI: -0.160 âˆ¼ -0.009) were significantly associated with the frequency of NSSI in adolescents with MDD, but emotional abuse (ß = 0.884, 95 % CI: 0.570-1.197), sexual abuse (ß = 0.825, 95 % CI: 0.527-1.124) and negative coping style (ß = 0.370, 95 % CI: 0.036-0.704) were independently associated with the depressive severity in these adolescents. Furthermore, the mediation analysis demonstrated that positive coping style partially mediates the effect of childhood trauma on NSSI (Indirect effect = 0.002, 95 % bootCI: 0.001-0.004), while the negative coping style partially mediates the relationship between childhood trauma and depressive severity (Indirect effect = 0.024, 95 % bootCI: 0.005-0.051) in adolescents with MDD. LIMITATIONS: A cross-sectional design, the retrospective self-reported data, the small sample size. CONCLUSION: Our findings suggest that coping styles may serve as mediators on the path from childhood trauma to NSSI or depressive severity in MDD adolescents.

A Novel Infrapatellar Fat Pad Preservation Technique in Total Knee Arthroplasty Reduced Postoperative Pain and Wound Complications.

OBJECTIVE: The management of the infrapatellar fat pad (IPFP) during total knee arthroplasty (TKA) remains controversial. This study aimed to evaluate a novel IPFP preservation technique-"the medially pedicled IPFP flap"-for reducing postoperative pain, wound complications, and improving functional recovery after TKA. METHODS: A retrospective analysis was conducted on TKA cases at our institution from 2018 to 2021, including those with IPFP preservation (medially pedicled flap) versus IPFP complete resection. Patient demographics, perioperative parameters (blood loss, operative time, length of hospital stay, visual analogue scale [VAS] score, white cell count [WBC], C-reactive protein [CRP], erythrocyte sedimentation rate [ESR], and wound oozing), and postoperative follow-up data (VAS, Knee Society [KSS], or Knee Society functional assessment [KSFA] scores) were compared between groups. Independent sample t-tests were used to compare continuous data and chi-squared tests were used to compare categorical data between groups. RESULTS: Six hundred thirty patients were included, with 278 in the medial pedicled IPFP flap group (preservation group) and 352 in the IPFP resection group (resection group). The operative time was significantly shorter in the preservation versus resection group (125.5 ± 23.2 vs 130.3 ± 28.7 mins, p = 0.03), as was the length of hospital stay (8.4 ± 2.7 vs 9.2 ± 2.3 days, p < 0.01). Regarding pain, the preservation group had significantly lower VAS scores on postoperative day 2 (2.0 ± 0.8 vs 2.4 ± 1.2, p < 0.001) and day 3 (1.5 ± 0.5 vs 1.8 ± 1.0, p < 0.001). CRP and ESR levels on postoperative day 5 were also significantly lower in the preservation group. Wound oozing rates were significantly lower in the preservation versus resection group (0.7% vs 2.8%, p = 0.04). No significant differences existed in VAS, KSS, or KSFA scores at the last follow-up. CONCLUSION: The novel IPFP preservation technique significantly improved surgical exposure, shortened operative time and length of hospital stay. It also reduced wound pain and oozing compared to IPFP resection.

Prosthetic spacers in two-stage revision for knee periprosthetic joint infection achieve better function and similar infection control.

Aims: To explore the clinical efficacy of using two different types of articulating spacers in two-stage revision for chronic knee periprosthetic joint infection (kPJI). Methods: A retrospective cohort study of 50 chronic kPJI patients treated with two types of articulating spacers between January 2014 and March 2022 was conducted. The clinical outcomes and functional status of the different articulating spacers were compared. Overall, 17 patients were treated with prosthetic spacers (prosthetic group (PG)), and 33 patients were treated with cement spacers (cement group (CG)). The CG had a longer mean follow-up period (46.67 months (SD 26.61)) than the PG (24.82 months (SD 16.46); p = 0.001). Results: Infection was eradicated in 45 patients overall (90%). The PG had a better knee range of motion (ROM) and Knee Society Score (KSS) after the first-stage revision (p = 0.004; p = 0.002), while both groups had similar ROMs and KSSs at the last follow-up (p = 0.136; p = 0.895). The KSS in the CG was significantly better at the last follow-up (p = 0.013), while a larger percentage (10 in 17, 58.82%) of patients in the PG chose to retain the spacer (p = 0.008). Conclusion: Prosthetic spacers and cement spacers are both effective at treating chronic kPJI because they encourage infection control, and the former improved knee function status between stages. For some patients, prosthetic spacers may not require reimplantation.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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).

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.