Polymerized Network-Based Artificial Peroxisome Reprogramming Macrophages for Photoacoustic Imaging-Guided Treatment of Rheumatoid Arthritis.

Artificial peroxisomes (AP) with enzyme-mimetic catalytic activity and recruitment ability have drawn a great deal of attention in fabricating protocell systems for scavenging reactive oxygen species (ROS), modulating the inflammatory microenvironment, and reprogramming macrophages, which is of great potential in treating inflammatory diseases such as rheumatoid arthritis (RA). Herein, a macrophage membrane-cloaked Cu-coordinated polyphthalocyanine-based AP (CuAP) is prepared with a macrocyclic conjugated polymerized network and embedded Cu-single atomic active center, which mimics the catalytic activity and coordination environment of natural superoxide dismutase and catalase, possesses the inflammatory recruitment ability of macrophages, and performs photoacoustic imaging (PAI)-guided treatment. The results of both in vitro cellular and in vivo animal experiments demonstrated that the CuAP under ultrasound and microbubbles could efficiently scavenge excess ROS in cells and tissues, modulate microenvironmental inflammatory cytokines such as interleukin-1ß, tumor necrosis factor-α, and arginase-1, and reprogram macrophages by polarization of M1 (proinflammatory phenotype) to M2 (anti-inflammatory phenotype). We believe this study offers a proof of concept for engineering multifaceted AP and a promising approach for a PAI-guided treatment platform for RA.

Microwave pretreatment effects on the aroma precursors, sensory characteristics and flavor profiles of fragrant rapeseed oil.

Microwave technology offers a rapid and uniform heating method. This study investigated how microwave pretreatment affects the aroma precursors and flavor of fragrant rapeseed oils (FROs). Microwave pretreatment led to decreased levels of polyunsaturated fatty acids, sugars, protein-bound amino acids, and glucosinolates. Using gas chromatography-mass spectrometry, we identified 66 volatile compounds in the oil samples. Among these, based on odor activity values (OAV ≥ 1), we found 9 aldehydes, 1 ketone, 6 pyrazines, 1 isothiocyanate, and 7 nitriles as the key aroma-active compounds, contributing fatty-like, nutty-like, and pungent-like odors, respectively. The electronic nose results highlighted W5S and W1W as primary sensors for determining the flavor profiles of FROs. Notably, aroma-active pyrazines exhibited strong negative correlations with sucrose, cysteine, lysine, and isoleucine. This research provides essential insights for enhancing the aroma of FROs.

Significance of the total renal chronicity score in predicting renal outcome in PLA2R-associated membranous nephropathy.

BACKGROUND: Phospholipase A2 receptor (PLA2R)-associated membranous nephropathy accounts for the majority of membranous nephropathy; however, few studies have determined the prognostic impact and clinical application of renal pathologic change on this disease. METHODS: A retrospective cohort study of 262 patients with PLA2R-associated membranous nephropathy was conducted. The total renal chronicity score calculated according to the degree of glomerulosclerosis, interstitial fibrosis, tubular atrophy, and arteriosclerosis was applied to evaluate renal chronicity. Baseline bias was adjusted by inverse probability weight when assessing the prognostic impact of chronicity, and multiple parameters were used to evaluate the application value of renal chronicity. RESULTS: During a median follow-up of 24.5 months, renal outcome (kidney function deterioration and/or end-stage kidney disease) was observed in 22 (8.40%) patients. Not only did a higher total renal chronicity score independently predict renal outcome [odds ratio (OR): 1.562, 95% confidence interval (CI) 1.073-2.273, P = 0.020], but non-minimal chronicity was also an independent risk factor for renal outcome (OR: 3.170, 95% CI 1.040-9.659, P = 0.042). Moreover, the membranous nephropathy risk classification in the Kidney Disease: Improving Global Outcomes (KDIGO) guideline integrated with non-minimal chronicity showed improvements in categorical net reclassification (0.174, 95% CI 0.012-0.335, P = 0.035), continuous net reclassification (0.462, 95% CI 0.087-0.838, P = 0.016), and integrated discrimination (0.019, 95% CI 0.003-0.035, P = 0.020) compared to the original classification. CONCLUSIONS: Renal chronicity is closely associated with renal outcomes in PLA2R-associated membranous nephropathy, and combining the KDIGO risk classification with chronicity scores may provide a more accurate prognostic prediction.

TP63 truncating mutation causes increased cell apoptosis and premature ovarian insufficiency by enhanced transcriptional activation of CLCA2.

BACKGROUND: Premature ovarian insufficiency (POI) is a severe disorder leading to female infertility. Genetic mutations are important factors causing POI. TP63-truncating mutation has been reported to cause POI by increasing germ cell apoptosis, however what factors mediate this apoptosis remains unclear. METHODS: Ninety-three patients with POI were recruited from Beijing Obstetrics and Gynecology Hospital, Capital Medical University. Whole-exome sequencing (WES) was performed for each patient. Sanger sequencing was used to confirm potential causative genetic variants. A minigene assay was performed to determine splicing effects of TP63 variants. A TP63-truncating plasmid was constructed. Real-time quantitative PCR, western blot analyses, dual luciferase reporter assays, immunofluorescence staining, and cell apoptosis assays were used to study the underlying mechanism of a TP63-truncating mutation causing POI. RESULTS: By WES of 93 sporadic patients with POI, we found a 14-bp deletion covering the splice site in the TP63 gene. A minigene assay demonstrated that the 14-bp deletion variant led to exon 13 skipping during TP63 mRNA splicing, resulting in the generation of a truncated TP63 protein (TP63-mut). Overexpression of TP63-mut accelerated cell apoptosis. Mechanistically, the TP63-mut protein could bind to the promoter region of CLCA2 and activate the transcription of CLCA2 several times compared to that of the TP63 wild-type protein. Silencing CLCA2 using a specific small interfering RNA (siRNA) or inhibiting the Ataxia Telangiectasia Mutated (ATM) pathway using the KU55933 inhibitor attenuated cell apoptosis caused by TP63-mut protein expression. CONCLUSION: Our findings revealed a crucial role for CLCA2 in mediating apoptosis in POI pathogenesis, and suggested that CLCA2 is a potential therapeutic target for POI.

Second Near-Infrared Macrophage-Biomimetic Nanoprobes for Photoacoustic Imaging of Neuroinflammation.

Neuroinflammation is a significant pathological event involving the neurodegenerative process associated with many neurological disorders. Diagnosis and treatment of neuroinflammation in its early stage are essential for the prevention and management of neurological diseases. Herein, we designed macrophage membrane-coated photoacoustic (PA) probes (MSINPs), with targeting specificities based on naturally existing target-ligand interactions for the early diagnosis of neuroinflammation. The second near-infrared dye, IR1061, was doped into silica as the core and was encapsulated with a macrophage membrane. In vitro as well as in vivo, the MSINPs could target inflammatory cells via the inflammation chemotactic effect. PA imaging was used to trace the MSINPs in a neuroinflammation mouse model and showed a great targeted effect of MSINPs in the prefrontal cortex. Therefore, the biomimetic nanoprobe prepared in this study offers a new strategy for PA molecular imaging of neuroinflammation, which can enhance our understanding of the evolution of neuroinflammation in specific brain regions.

Transformation of A1/A2 Astrocytes Participates in Brain Ischemic Tolerance Induced by Cerebral Ischemic Preconditioning via Inhibiting NDRG2.

Cerebral ischemic preconditioning (CIP) has been shown to improve brain ischemic tolerance against subsequent lethal ischemia. Reactive astrocytes play important roles in cerebral ischemia-reperfusion. Recent studies have shown that reactive astrocytes can be polarized into neurotoxic A1 phenotype (C3d) and neuroprotective A2 phenotype (S100A10). However, their role in CIP remains unclear. Here, we focused on the role of N-myc downstream-regulated gene 2 (NDRG2) in regulating the transformation of A1/A2 astrocytes and promoting to brain ischemic tolerance induced by CIP. A Sprague Dawley rat model of middle cerebral artery occlusion/reperfusion (MCAO/R) was used. Rats were divided into the following six groups: (1) sham group; (2) CIP group: left middle cerebral artery was blocked for 10 min; (3) MCAO/R group: left middle cerebral artery was blocked for 90 min; (4) CIP + MCAO/R group: CIP was performed 72 h before MCAO/R; (5) AAV-NDRG2 + CIP + MCAO/R group: adeno-associated virus (AAV) carrying NDRG2 was administered 14 days before CIP + MCAO/R; (6) AAV-Ctrl + CIP + MCAO/R group: empty control group. The rats were subjected to neurological evaluation 24 h after the above treatments, and then were sacrificed for 2, 3, 5-triphenyltetraolium chloride staining, thionin staining, immunofluorescence and western blot analysis. In CIP + MCAO/R group, the neurological deficit scores decreased, infarct volume reduced, and neuronal density increased compared with MCAO/R group. Notably, CIP significantly increased S100A10 expression and the number of S100A10+/GFAP+ cells, and also increased NDRG2 expression. MCAO/R significantly decreased S100A10 expression and the number of S100A10+/GFAP+ cells yet increased C3d expression and the number of C3d+/GFAP+ cells and NDRG2 expression, and these trends were reversed by CIP + MCAO/R. Furthermore, over-expression of NDRG2 before CIP + MCAO/R, the C3d expression and the number of C3d+/GFAP+ cells increased, while S100A10 expression and the number of S100A10+/GFAP+ cells decreased. Meanwhile, over-expression of NDRG2 blocked the CIP-induced brain ischemic tolerance. Taken together, these results suggest that CIP exerts neuroprotective effects against ischemic injury by suppressing A1 astrocyte polarization and promoting A2 astrocyte polarization via inhibiting NDRG2 expression.

Rapamycin mitigates organ damage by autophagy-mediated NLRP3 inflammasome inactivation in sepsis.

Autophagy activation can alleviate sepsis-induced organ injuries. Rapamycin (Rap) has emerged as an autophagy regulator in multiple forms of organ injuries. This study aimed to assess whether Rap protects rats from cecal ligation and puncture (CLP)-induced sepsis through autophagy-mediated inactivation of the NLRP3 inflammasome. Rats were allocated to the sham, CLP, Rap (10 mg/kg), or 3-Methyladenine (3-MA) (15 mg/kg) groups. A rat CLP model was established. The survival of rats and lung wet-to-dry weight ratio in each group was assessed. Blood biochemical indexes and oxidative stress-related factors were analyzed with an automatic biochemical analyzer. The bacterial counts of blood and organs were monitored. The degrees of myeloperoxidase of the ileum, inflammation-related indexes, and pathological changes in the tissues were detected by ELISA and hematoxylin-eosin staining. The levels of NLRP3 inflammasome and autophagy-related factors were analyzed by Western blot. Rap increased the survival and SOD activity, and repressed ALT, AST, BUN, SCr, MDA, and inflammation-related marker levels in CLP rats, it also restrained the bacterial counts of blood, lung, liver, and kidney in CLP rats; the effects of 3-MA on CLP rats on the above-mentioned indicators were opposite to those of Rap. Additionally, Rap alleviated the pathological injury of the lung, liver, and kidney, which was the opposite to the effect of 3-MA on CLP rats. Furthermore, Rap mitigated the ASC, Pro-caspase 1, and NLRP3 levels and increased the Beclin-1 levels and the LC3II/LC3I ratio in the organ tissues. Collectively, autophagy activation can mitigate organ damage by suppressing the NLRP3 inflammasome in sepsis rats.

Silenced-C5ar1 improved multiple organ injury in sepsis rats via inhibiting neutrophil extracellular trap.

Sepsis has a systemic inflammatory response syndrome caused by infection. While neutrophils play contradictory roles in different stages of sepsis. Neutrophils have been proven to play an antibacterial role by producing neutrophil extracellular traps (NETs). Although the NET is beneficial to bacteria resistance, abnormal NET increases tissue damage. The complement C5a receptor 1 (C5ar1) is a gene related to strong inflammatory reactions and is found to be associated with inflammatory factors. This study found that there were 45 down-regulated genes and 704 up-regulated genes in sepsis rats by transcriptome sequencing. And those genes were significantly related to inflammation and immunity by GO and KEGG enrichment analysis involving the chemokine signaling pathway, the Toll-like receptor (TLR) signaling pathway, and the Fc gamma R-mediated phagocytosis. Additionally, the C5ar1 gene was significantly upregulated with interesting potential in sepsis and used for further study. This study used cecum ligation and puncture (CLP) rats that were respectively injected intravenously with PBS or the lentivirus vector to explore the effect of C5ar1 on CLP rats. It demonstrated that silenced- C5ar1 inhibited the ALT, AST, BUN, and CREA levels, improved the lung and spleen injury, and reduced the TNF-α, IL-6, IL-1ß, IL-10, cf-DNA, and cfDNA/MPO levels. Additionally, silenced C5ar1 inhibited the TLR2, TLR4, and peptidylarginine deiminase 4 expression levels, which suggested the improvement of silenced C5ar1 on sepsis via inhibiting NETs and the TLR signaling pathway. This study provides a basis and new direction for the study of treatment on sepsis.

Multiparametric Cardiovascular Magnetic Resonance in Nonhospitalized COVID-19 Infection Subjects: An Intraindividual Comparison Study.

PURPOSE: To investigate intraindividual cardiac structural and functional changes before and after COVID-19 infection in a previously healthy population with a 3T cardiac magnetic resonance (CMR). MATERIALS AND METHODS: A total of 39 unhospitalized patients with COVID-19 were recruited. They participated in our previous study as non-COVID-19 healthy volunteers undergoing baseline CMR examination and were recruited to perform a repeated CMR examination after confirmed COVID-19 infection in December 2022. The CMR parameters were measured and compared between before and after COVID-19 infection with paired t tests. The laboratory measures including myocardial enzymes and inflammatory indicators were also collected when performing repeated CMR. RESULTS: The median duration was 393 days from the first to second CMR and 26 days from clinical symptoms onset to the second CMR. Four patients (10.3%, 4/39) had the same late gadolinium enhancement pattern at baseline and repeated CMR and 5 female patients (12.8%, 5/39) had myocardial T2 ratio >2 (2.07 to 2.27) but with normal T2 value in post-COVID-19 CMR. All other CMR parameters were in normal ranges before and after COVID-19 infection. Between before and after the COVID-19 infection, there were no significant differences in cardiac structure, function, and tissue characterization, no matter with or without symptoms (fatigue, chest discomfort, palpitations, shortness of breath, and insomnia/sleep disorders) (all P >0.05). The laboratory measures at repeated CMR were in normal ranges in all participants. CONCLUSIONS: These intraindividual CMR studies showed unhospitalized patients with COVID-19 with normal myocardial enzymes had no measurable CMR abnormalities, which can help alleviate wide social concerns about COVID-19-related myocarditis.

STAT4-Mediated Klotho Up-Regulation Contributes to the Brain Ischemic Tolerance by Cerebral Ischemic Preconditioning via Inhibiting Neuronal Pyroptosis.

Our previous study has proved that the Klotho up-regulation participated in cerebral ischemic preconditioning (CIP)-induced brain ischemic tolerance. However, the exact neuroprotective mechanism of Klotho in CIP remains unclear. We explored the hypothesis that STAT4-mediated Klotho up-regulation contributes to the CIP-induced brain ischemic tolerance via inhibiting neuronal pyroptosis. Firstly, the expressions of pyroptosis-associated proteins (i.e., NLRP3, GSDMD, pro-caspase-1, and cleaved caspase-1) in hippocampal CA1 region were determined during the process of brain ischemic tolerance. We found the expression of pyroptosis-associated proteins was significantly up-regulated in the ischemic insult (II) group, and showed no significant changes in the CIP group. The expression level of each pyroptosis-associated proteins was lower in the CIP + II group than that in the II group. Inhibition of Klotho expression increased the expression of pyroptosis-associated proteins in the CIP + II group and blocked the CIP-induced brain ischemic tolerance. Injection of Klotho protein decreased the expression of pyroptosis-associated proteins in the II group, and protected neurons from ischemic injury. Secondly, the transcription factor STAT4 of Klotho was identified by bioinformatic analysis. Double luciferase reporter gene assay and chromatin immunoprecipitation assay showed STAT4 can bind to the site between nt - 881 and - 868 on the Klotho promoter region and positively regulates Klotho expression. Moreover, we found CIP significantly enhanced the expression of STAT4. Knockdown STAT4 suppressed Klotho up-regulation after CIP and blocked the CIP-induced brain ischemic tolerance. Collectively, it can be concluded that STAT4-mediated the up-regulation of Klotho contributed to the brain ischemic tolerance induced by CIP via inhibiting pyroptosis.

The Role of Astrocytic Mitochondria in the Pathogenesis of Brain Ischemia.

The morbidity rate of ischemic stroke is increasing annually with the growing aging population in China. Astrocytes are ubiquitous glial cells in the brain and play a crucial role in supporting neuronal function and metabolism. Increasing evidence shows that the impairment or loss of astrocytes contributes to neuronal dysfunction during cerebral ischemic injury. The mitochondrion is increasingly recognized as a key player in regulating astrocyte function. Changes in astrocytic mitochondrial function appear to be closely linked to the homeostasis imbalance defects in glutamate metabolism, Ca2+ regulation, fatty acid metabolism, reactive oxygen species, inflammation, and copper regulation. Here, we discuss the role of astrocytic mitochondria in the pathogenesis of brain ischemic injury and their potential as a therapeutic target.

lncRNA-Gm5532 regulates osteoclast differentiation through the miR-125a-3p/TRAF6 axis.

Long noncoding RNAs (lncRNAs) are important regulators of bone metabolism. In this study, lncRNA microarray analysis was used to identify differentially expressed lncRNAs in differentiated osteoclasts. lncRNA-Gm5532 is highly expressed during osteoclast differentiation. lncRNA-Gm5532 knockdown impairs osteoclast formation and bone resorption. Mechanistic experiments show that lncRNA-Gm5532 functions as a competing endogenous RNA (ceRNA) and acts as a sponge for miR-125a-3p, which promotes TNF receptor-associated factor 6 (TRAF6) expression. miR-125a-3p mimics suppress osteoclast differentiation and TAK1/NF-κB/MAPK signaling. The miR-125a-3p inhibitor reverses the negative effects of siGm5532 on osteoclast differentiation. In summary, our study reveals that lncRNA-Gm5532 functions as an activator in osteoclast differentiation by targeting the miR-125a-3p/TRAF6 axis, making it a novel biomarker and potential therapeutic target for osteoporosis.

Ultrasound-based detection of inflammatory changes for early diagnosis and risk model construction of psoriatic arthritis.

OBJECTIVES: Psoriatic arthritis (PsA) is the most prevalent coexisting condition associated with psoriasis. Early-stage PsA patients always present unspecific and subtle clinical manifestations causing delayed diagnosis and leading to unfavorable health outcomes. The application of ultrasound enables precise identification of inflammatory changes in musculoskeletal structures. Hence, we constructed ultrasound models to aid early diagnosis of PsA. METHODS: This is a cross-sectional study carried out in the Department of Dermatology at West China Hospital (October 2018-April 2021). All participants underwent thorough ultrasound examinations. Participants were classified into the under 45 group (18 ≤ age ≤ 45) and over 45 group (age > 45) and then randomly grouped into derivation and test cohort (7:3). Univariable logistic regression, least absolute shrinkage and selection operator, and multivariable logistic regression visualized by nomogram were conducted in order. Receiver operating characteristic (ROC), calibration curve, decision curve analysis (DCA), and clinical impact curve analysis (CICA) were performed for model verification. RESULTS: A total of 1256 participants were included, with 767 participants in the under 45 group and 489 in the over 45 group. Eleven and sixteen independent ultrasonic variables were finally selected to construct the under 45 and over 45 model with the area under the ROC of 0.83 (95%CI: 0.78-0.87) and 0.83 (95%CI: 0.78-0.88) in derivation cohort, respectively. The DCA and CICA analyses showed good clinical utility of the two models. CONCLUSION: The implementation of the ultrasound models could streamline the diagnostic process for PsA in psoriasis patients, leading to expedited evaluations while maintaining diagnostic accuracy.

NRF2 is essential for iron-overload stimulated osteoclast differentiation through regulation of redox and iron homeostasis.

Iron overload enhances osteoclastic bone resorption and induces osteoporosis. Excess iron is highly toxic. The modulation of redox and iron homeostasis is critical for osteoclast differentiation under iron-overload condition. Nuclear factor erythroid 2-related factor 2 (NRF2) is a transcription factor that regulates the cellular defense against oxidative stress and iron overload through the expression of genes involved in anti-oxidative processes and iron metabolism. Our studies demonstrated that NRF2 activation was suppressed during osteoclast differentiation. Under iron-overload condition, NRF2 and its mediated antioxidant and iron metabolism genes were activated by reactive oxygen species (ROS), which enhanced antioxidant capability. NRF2 mediated the upregulation of iron exporter ferroportin 1 (FPN1) and iron storage protein ferritin, contributing to decreased levels of intracellular iron. Nfe2l2 knockout induced oxidative stress and promoted osteoclast differentiation under normal condition, but induced ferroptosis under iron-overload condition. Nfe2l2 knockout alleviated iron overload induced bone loss by inhibiting osteoclast differentiation. Our results suggest that NRF2 activation is essential for osteoclast differentiation by enhancing antioxidant capability and reducing intracellular iron under iron-overload condition. Targeting NRF2 to induce ferroptosis could be a potential therapy for the treatment of iron-overload induced osteoporosis.

Defining Biventricular Abnormalities by Cardiac Magnetic Resonance in Pre-Dialysis Patients with Chronic Kidney Disease.

Introduction: The aim of the study was to investigate biventricular structural and functional abnormalities in pre-dialysis patients across stages of chronic kidney disease (CKD) by cardiac magnetic resonance (CMR). Methods: Fifty-one CKD patients with CMR exams were retrospectively analyzed. Patients were divided into three groups according to estimated glomerular filtration rate (eGFR): CKD 1 group (patients with normal eGFR≥90 mL/min/1.73 m2, n = 20), CKD 2-3 group (patients with eGFR< 90 to ≥30 mL/min/1.73 m2, n = 14), and CKD 4-5 group (patients with eGFR<30 mL/min/1.73 m2, n = 17). Twenty-one age- and sex-matched healthy controls (HC) were recruited. CMR-derived left ventricular (LV) and right ventricular (RV) structural and functional measures were compared. Association between CMR parameters and clinical measures was assessed. Results: There was an increasing trend in RV mass index (RVMi) and LV mass index (LVMi) with the occurrence and development of CKD from HC group to CKD 4-5 group although no significant difference was observed between CKD 1 group and HC group. LV global radial strain and LV global circumferential strain dropped and native T1 value elevated significantly in CKD 4-5 group compared with the other three groups (all p < 0.05), while RV strain measures, RV ejection fraction, and LV ejection fraction showed no significant difference among 4 groups (all p > 0.05). Elevated LV end-diastolic volume index (ß = 0.356, p = 0.016) and RV end-systolic volume index (ß = 0.488, p = 0.001) were independently associated with RVMi. Increased systolic blood pressure (ß = 0.309, p = 0.004), LV end-systolic volume index (ß = 0.633, p < 0.001), and uric acid (ß = 0.261, p = 0.013) were independently associated with LVMi. Meanwhile, serum phosphorus (ß = 0.519, p = 0.001) was independently associated with native T1 value. Conclusion: In pre-dialysis CKD patients, left and right ventricular remolding has occurred. RVMi and LVMi were the first changed CMR indexes in the development of CKD when eGFR began to drop. Because fluid volume overload was the independent risk factor for RVMi and LVMi increase, reasonable controlling fluid volume overload may slow down the progression of biventricular remolding and may reduce related cardiovascular disease risk.

A Low-Profile Dielectric Resonator Filter with Wide Stopband for High Integration on PCB.

A low-profile dielectric resonator (DR) filter is proposed to achieve the feature of high integration and wide stopband. The high integration is due to the structure of printed circuit board (PCB) substrate instead of metal cavity, which can be easily integrated with other planar circuits. Thus, the proposed design can improve the integration level and reduce installation errors. Moreover, the out-of-band harmonics can be well suppressed by the structure combined with introducing rectangular hollowing in the center of the dielectric block, coupling the feed and loading 1/4λ wavelength branch. For demonstration, it is fabricated and measured. The simulated and experimental results with good agreement are presented, the insertion loss is as low as 1.1 dB, the profile height is only 0.77λg, and the stopband reaches 2.61f0.

Association between endometriosis and metabolic syndrome: a cross-sectional study based on the National Health and Nutrition Examination Survey data.

BACKGROUND: Endometriosis has been reported to be associated with metabolism-related diseases, such as hypercholesterolemia and diabetes, while no studies have reported the association between endometriosis and metabolic syndrome. OBJECTIVE: This study aims to explore the association between endometriosis and metabolic syndrome. Also, the association between endometriosis and single metabolic syndrome indicator was explored. METHODS: This was a cross-sectional study based on the National Health and Nutrition Examination Survey (NHANES). A total of 2389 participants were finally included for analysis, with 2212 in the non-endometriosis group and 177 in the endometriosis group. Association between endometriosis and metabolic syndrome was explored using multivariate logistic regression analysis, with results shown as odds ratio (OR) with 95% confidence intervals (95%CI). Association between endometriosis and single metabolic syndrome indicator was explored using multivariate liner regression analysis. RESULTS: After adjusting age, race, education level, family poverty to income ratio (PIR), smoking, age at menarche, gravidity, menopause, female hormones use, and dyslipidemia drug use, endometriosis was associated with the higher odds of metabolic syndrome (OR = 1.55, 95%CI: 1.01-2.35). Further adjusting hysterectomy or oophorectomy, we found the similar association despite no statistical significance (OR = 1.47, 95%CI: 0.96-2.25). Moreover, we found endometriosis was associated with the high level of triglyceride (TG) (ß = 0.38, 95%CI: 0.06-0.70). CONCLUSIONS: Our study found the association between endometriosis and metabolic conditions, indicating that metabolic conditions of endometriosis women should be focused, and monitoring the blood lipid levels may be significant in decreasing the risk of metabolic syndrome.

Vertical Graphene-Based Printed Electrochemical Biosensor for Simultaneous Detection of Four Alzheimer's Disease Blood Biomarkers.

Early detection and timely intervention play a vital role in the effective management of Alzheimer's disease. Currently, the diagnostic accuracy for Alzheimer's disease based on a single blood biomarker is relatively low, and the combined use of multiple blood biomarkers can greatly improve diagnostic accuracy. Herein, we report a printed electrochemical biosensor based on vertical graphene (VG) modified with gold nanoparticles (VG@nanoAu) for the simultaneous detection of four Alzheimer's disease blood biomarkers. The printed electrochemical electrode array was constructed by laser etching and inkjet printing. Then gold nanoparticles were modified onto the working electrode surface via electrodeposition to further improve the sensitivity of the sensor. In addition, the entire printed electrochemical sensing system incorporates an electrochemical micro-workstation and a smartphone. The customized electrochemical micro-workstation incorporates four electro-chemical control chips, enabling the sensor to simultaneously analyze four biomarkers. Consequently, the printed electrochemical sensing system exhibits excellent analytical performance due to the large surface area, biocompatibility, and good conductivity of VG@nanoAu. The detection limit of the sensing system for Aß40, Aß42, T-tau, and P-tau181 was 0.072, 0.089, 0.071, and 0.051 pg/mL, respectively, which meets the detection requirements of Alzheimer's disease blood biomarkers. The printed electrochemical sensing system also exhibits good specificity and stability. This work has great value and promising prospects for early Alzheimer's disease diagnosis using blood biomarkers.

Hollow-polydopamine-nanocarrier-based near-infrared-light/pH-responsive drug delivery system for diffuse alveolar hemorrhage treatment.

Introduction: Diffuse alveolar hemorrhage (DAH) is a serious complication caused by systemic lupus erythematosus (SLE). Tissue damage and changes in immune response are all associated with excessive free radical production. Therefore, removing excess reactive oxygen species are considered a feasible scheme for diffuse alveolar hemorrhage treatment. Cyclophosphamide is often used as the main therapeutic drug in clinics. However, CTX carries a high risk of dose-increasing toxicity, treatment intolerance, and high recurrence rate. The combination of therapeutic drugs and functional nanocarriers may provide an effective solution. PDA is rich in phenolic groups, which can remove the reactive oxygen species generated in inflammatory reactions, and can serve as excellent free radical scavengers. Methods: We developed a hollow polydopamine (HPDA) nanocarrier loaded with CTX by ionization to prepare the novel nanoplatform, CTX@HPDA, for DAH treatment. The monodisperse silica nanoparticles were acquired by reference to the typical Stober method. PDA was coated on the surface of SiO2 by oxidation self-polymerization method to obtain SiO2@PDA NPs. Then, HPDA NPs were obtained by HF etching. Then HPDA was loaded with CTX by ionization to prepare CTX@HPDA. Then we tested the photothermal effect, animal model therapeutics effect, and biosafety of CTX@HPDA. Results: Material tests showed that the CTX@ HPDA nanoplatform had a uniform diameter and could release CTX in acidic environments. The vitro experiments demonstrated that CTX@HPDA has good photothermal conversion ability and photothermal stability. Animal experiments demonstrated that the CTX@HPDA nanoplatform had good biocompatibility. The nanoplatform can dissociate in acidic SLE environment and trigger CTX release through photothermal conversion. Combining HPDA, which scavenges oxygen free radicals, and CTX, which has immunosuppressive effect, can treat pulmonary hemorrhage in SLE. Micro-CT can be used to continuously analyze DAH severity and lung changes in mice after treatment. The pulmonary exudation in the various treatment groups improved to varying degrees. Discussion: In this study, we report a photothermal/PH-triggered nanocarrier (CTX@HPDA) for the precise treatment of SLE-DAH. CTX@HPDA is a simple and efficient nanocarrier system for DAH therapy. This work provides valuable insights into SLE treatment.