Reduced FNDC5-AMPK signaling in diabetic atrium increases the susceptibility of atrial fibrillation by impairing mitochondrial dynamics and activating NLRP3 inflammasome.

Fibronectin type III domain-containing protein 5 (FNDC5) exerts potential anti-arrhythmic effects. However, the function and mechanism of FNDC5 in diabetes-associated atrial fibrillation (AF) remain unknown. In this study, bioinformatics analysis, in vivo and in vitro experiments were conducted to explore the alteration and role of FNDC5 in diabetes-related atrial remodeling and AF susceptibility. RNA sequencing data from atrial samples of permanent AF patients and diabetic mice exhibited significantly decreased FNDC5 at the transcriptional level, which was in line with the protein expression in diabetic mice as well as high glucose and palmitic acid (HG+PA) injured atrial myocytes. Diabetic mice exhibited adverse atrial remodeling and increased AF inducibility. Moreover, reduced atrial FNDC5 was accompanied with exacerbated NOD-like receptor pyrin domain containing 3 (NLRP3) activation and disturbed mitochondrial fission and fusion processes, as evidenced by decreased expressions of optic atrophy 1 (OPA-1), mitofusin (MFN-1, MFN-2) and increased phosphorylation of dynamin-related protein 1 (Ser616). These effects were validated in HG+PA-treated atrial myocytes. Critically, FNDC5 overexpression remarkably enhanced cellular antioxidant capacity by upregulating the expressions of superoxide dismutase (SOD1, SOD2) level. In addition, HG+PA-induced mitochondrial dysfunction was ameliorated by FNDC5 overexpression as evidenced by improved mitochondrial dynamics and membrane potential. Moreover, NLRP3 inflammasome-mediated inflammation was reduced by FNDC5 overexpression, and AMPK signaling might serve as the key down-stream effector. The present study demonstrated that reduced atrial FNDC5-AMPK signaling contributed to the pathogenesis of diabetes- associated AF by impairing mitochondrial dynamics and activating the NLRP3 inflammasome. These findings provide promising therapeutic avenues for diabetes-associated AF.

ENDOLUMINAL RADIOFREQUENCY ABLATION WITH STENTING VS STENTING ONLY IN PATIENTS WITH MALIGNANT BILIARY OBSTRUCTION: A META-ANALYSIS OF RANDOMISED TRIALS.

INTRODUCTION: Endoluminal radiofrequency ablation (RFA) is a palliative treatment for patients suffering from malignant biliary obstruction. We aimed to conduct a meta-analysis to evaluate the impact of RFA on stent patency, patient survival, and adverse events. METHODS: Major databases were searched through November 2023 for patients who underwent stenting with or without RFA for extra-hepatic malignant biliary obstruction. A random effects model was employed for analysis and results conveyed using relative risk ratio with 95% confidence interval. RESULTS: Nine RCTs involving 750 subjects (n=374 RFA plus stent vs. n=376 stent only) with malignant biliary obstruction were included. Meta-analysis revealed similar risks of stent patency at 3 months (RR = 1.01; 95% CI [0.92 - 1.11], I2=4% for RFA plus stenting vs. stent only). Meta-analysis showed improved survival at 6 months (RR = 0.84; 95% CI [0.73 - 0.96], I2=21%, P=0.01 for RFA plus stenting vs. stent only). Subgroup analysis comparing plastic vs uncovered metal stents showed that stent patency was unaffected at 3 months (RR = 1.06; 95% CI [0.91 - 1.23]; I2=17%). Subgroup analysis showed that patients with cholangiocarcinoma experienced an overall survival benefit with RFA plus stenting vs. stent only (P<0.001), however, stent patency remained unaffected (P=0.08). An increased incidence of cholecystitis was noted with RFA plus stent vs. stent only (5.1%; 95% CI [3.1% - 7.8%] vs 0.3%; 95% CI [0.01% - 1.5%], respectively). CONCLUSION: Combining endoluminal RFA and stenting may improve overall survival in patients with malignant biliary obstruction. RFA did not impact stent patency significantly.

Diagnostic meta-analysis of the efficacy of ultrasonography for diagnosing carpal tunnel syndrome: A comparison between Asian and non-Asian populations.

BACKGROUND: Ultrasonography is used to diagnose carpal tunnel syndrome (CTS) according to various criteria. This diagnostic meta-analysis aimed to evaluate the efficacy of ultrasonography for diagnosing CTS, focusing on the cross-sectional area (CSA) of the median nerve (MN) at the inlet of the carpal tunnel and regional variations in diagnostic thresholds between Asian and non-Asian populations. METHODS: A comprehensive literature search was conducted using PubMed, Embase, and the Cochrane Library. The risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2). Patient demographic data, diagnostic "gold standards", CSA cutoff values, and diagnostic results were extracted. Meta-analysis was performed to determine the sensitivity, specificity, and optimal CSA cutoff values. RESULTS: For the 25 included studies, a combined sensitivity of 88% and specificity of 84% for CSA measurements at the carpal tunnel inlet were obtained. The Asian group had a sensitivity of 84% and specificity of 86%, while the non-Asian group had a sensitivity of 91% and specificity of 82%. The mean CSA in the Asian group was significantly lower than that in the non-Asian group (12.93 mm2 and 14.77 mm2, respectively; p = 0.042). For the Asian group, the summary receiver operating characteristic curve had an area under the curve (AUC) of 0.92 with an optimal cutoff of 10.5 mm2; for the non-Asian group, an AUC of 0.94 was obtained with a cutoff of 11.5 mm2. CONCLUSION: Ultrasonography is a reliable diagnostic method for CTS, with distinct optimal cutoff values observed between Asian and non-Asian populations. Therefore, population-specific diagnostic criteria for CTS are recommended.

Rhizoma coptidis can inhibit the excessive proliferation, inflammation, and transformation of lung fibroblasts into myofibroblasts.

BACKGROUND: Pulmonary fibrosis (PF) is a chronic, progressive, and irreversible heterogeneous disease of lung interstitial tissue. To combat progression of PF, new drugs are required to be developed. Rhizoma coptidis (COP), one of the main alkaloids of Coptis chinensis, is a traditional herbal medicine used to treat various inflammatory diseases. OBJECTIVE: To investigate the possible effects of Coptisine (Cop) on the growth, inflammation, as well as FMT of TNF-ß1-induced HFL1 cells and uncover the mechanism. MATERIAL AND METHODS: Human fetal lung fibroblast 1 (HFL1) was induced using 6ng/mL TGF-ß1 as a model of pulmonary fibrosis. CCK-8, Brdu, and transwell assays indicated the effects on cell growth as well as motility. qPCR and the corresponding kits indicted the effects on cell inflammation. Immunoblot showed the effects on FMT and further confirmed the mechanism. RESULTS: Coptisine inhibits excessive growth as well as motility of TNF-ß1-induced HFL1 cells. It further inhibits inflammation and ROS levels in TNF-ß1-induced HFL1 cells. Coptisine inhibits the FMT process of TNF-ß1-induced HFL1 cells. Mechanically, coptisine promotes the Nrf2/HO-1 pathway. CONCLUSION: Coptisine can inhibit the excessive growth, inflammation as well as FMT of lung fibroblasts into myofibroblasts. It could serve as a promising drug of PF.

A Photoelectrochemical Retinomorphic Synapse.

Reproducing human visual functions with artificial devices is a long-standing goal of the neuromorphic domain. However, emulating the chemical language communication of the visual system in fluids remains a grand challenge. Here, a "multi-color" hydrogel-based photoelectrochemical retinomorphic synapse is reported with unique chemical-ionic-electrical signaling in an aqueous electrolyte that enables, e.g., color perception and biomolecule-mediated synaptic plasticity. Based on the specific enzyme-catalyzed chromogenic reactions, three multifunctional colored hydrogels are developed, which can not only synergize with the Bi2S3 photogate to recognize the primary colors but also synergize with a given polymeric channel to promote the long-term memory of the system. A synaptic array is further constructed for sensing color images and biomolecule-coded information communication. Taking advantage of the versatile biochemistry, the biochemical-driven reversible photoelectric response of the cone cell is further mimicked. This work introduces rich chemical designs into retinomorphic devices, providing a perspective for replicating the human visual system in fluids.

Early inhibition of the ATM/p53 pathway reduces the susceptibility to atrial fibrillation and atrial remodeling following acute myocardial infarction.

Atrial fibrillation (AF) emerges as a critical complication following acute myocardial infarction (AMI) and is associated with a significant increased risk of heart failure, stroke and mortality. Ataxia telangiectasia mutated (ATM), a key player in DNA damage repair (DDR), has been implicated in multiple cardiovascular conditions, however, its involvement in the development of AF following AMI remains unexplored. This study seeks to clarify the contribution of the ATM/p53 pathway in the onset of AF post-AMI and to investigate the underlying mechanisms. The rat model of AMI was established by ligating left anterior descending coronary artery in the presence or absence of Ku55933 (an ATM kinase inhibitor, 5 mg/kg/d) treatment. Rats receiving Ku55933 were further divided into the early administration group (administered on days 1, 2, 4, and 7 post-AMI) and the late administration group (administered on days 8, 9, 11 and 14 post-AMI). RNA-sequencing was performed 14 days post-operation. In vitro, H2O2-challenged HL-1 atrial muscle cells were utilized to evaluate the potential effects of different ATM inhibition schemes, including earlier, middle, and late periods of intervention. Fourteen days post-AMI injury, the animals exhibited significantly increased AF inducibility, exacerbated atrial electrical/structural remodeling, reduced ventricular function and exacerbated atrial DNA damage, as evidenced by enhanced ATM/p53 signaling as well as γH2AX level. These effects were partially consistent with the enrichment results of bioinformatics analysis. Notably, the deleterious effects were ameliorated by early, but not late, administration of Ku55933. Mechanistically, inhibition of ATM signaling successfully suppressed atrial NLRP3 inflammasome-mediated pyroptotic pathway. Additionally, the results were validated in the in vitro experiments demonstrating that early inhibition of Ku55933 not only attenuated cellular ATM/p53 signaling, but also mitigated inflammatory response by reducing NLRP3 activation. Collectively, hyperactivation of ATM/p53 contributed to the pathogenesis of AF following AMI. Early intervention with ATM inhibitors substantially mitigated AF susceptibility and atrial electrical/structural remodeling, highlighting a novel therapeutic avenue against cardiac arrhythmia following AMI.

Digirseophene A promotes recovery in injured developing cerebellum via AMPK/AKT/GSK3ß pathway-mediated neural stem cell proliferation.

Neural stem cells (NSCs) exhibit a remarkable capacity for self-renewal and have the potential to differentiate into various neural lineage cells, which makes them pivotal in the management of neurological disorders. Harnessing the inherent potential of endogenous NSCs for enhancing nerve repair and regeneration represents an optimal approach to addressing diseases of the nervous system. In this study, we explored the potential of a novel benzophenone derivative named Digirseophene A (DGA), which was isolated from the endophytic fungus Corydalis tomentella. Previous experiments have extensively identified and characterized DGA, revealing its unique properties. Our findings demonstrate the remarkable capability of DGA to stimulate neural stem cell proliferation, both in vitro and in vivo. Furthermore, we established a model of radiation-induced cerebellar injury to assess the effects of DGA on the distribution of different cell subpopulations within the damaged cerebellum, thereby suggesting its beneficial role in cerebellar repair. In addition, our observations on a primary NSCs model revealed that DGA significantly increased cellular oxygen consumption, indicating increased energy and metabolic demands. By utilizing various pathway inhibitors in combination with DGA, we successfully demonstrated its ability to counteract the suppressive impacts of AMPK and GSK3ß inhibitors on NSC proliferation. Collectively, our research results strongly suggest that DGA, as an innovative compound, exerts its role in activating NSCs and promoting injury repair through the regulation of the AMPK/AKT/GSK3ß pathway.

Development and validation of a risk prediction model for motoric cognitive risk syndrome in older adults.

OBJECTIVE: The objective of this study was to develop a risk prediction model for motoric cognitive risk syndrome (MCR) in older adults. METHODS: Participants were selected from the 2015 China Health and Retirement Longitudinal Study database and randomly assigned to the training group and the validation group, with proportions of 70% and 30%, respectively. LASSO regression analysis was used to screen the predictors. Then, identified predictors were included in multivariate logistic regression analysis and used to construct model nomogram. The performance of the model was evaluated by area under the receiver operating characteristic (ROC) curve (AUC), calibration curves and decision curve analysis (DCA). RESULTS: 528 out of 3962 participants (13.3%) developed MCR. Multivariate logistic regression analysis showed that weakness, chronic pain, limb dysfunction score, visual acuity score and Five-Times-Sit-To-Stand test were predictors of MCR in older adults. Using these factors, a nomogram model was constructed. The AUC values for the training and validation sets of the predictive model were 0.735 (95% CI = 0.708-0.763) and 0.745 (95% CI = 0.705-0.785), respectively. CONCLUSION: The nomogram constructed in this study is a useful tool for assessing the risk of MCR in older adults, which can help clinicians identify individuals at high risk.

A comprehensive measure assessing different types of problematic use of the internet among Chinese adolescents: The Assessment of Criteria for Specific Internet-use Disorders (ACSID-11).

BACKGROUND: Problematic use of the internet (PUI) is prevalent, particularly among adolescents and young adults. Given the limited measures to assess specific types of PUI, which encompasses a broad spectrum of activities such as online gaming, social media use, pornography use, shopping, gambling, and web-streaming, Muller et al. (2022) developed the Assessment of Criteria for Specific Internet-use Disorders (ACSID-11) to comprehensively assess different types of PUI (i.e., gaming, shopping, social media use, gambling, and pornography use). The present study aimed to validate the Chinese ACSID-11 among adolescents incorporating cross-cultural adaptations. METHODS: Using forward-backward translation method, a culturally adapted version of the ACSID-11 was prepared. Then, a cross-sectional online survey was administered between September 8 and September 26, 2023. Adolescents, using a convenience sample (N = 11,492; mean age = 16.42 years [SD ± 0.91]; 59.1% male), were recruited from six schools to complete the translated ACSID-11, Internet Gaming Disorder Scale-Short Form (IGDS9-SF), Bergen Social Media Addiction Scale (BSMAS), and Smartphone Application Based Addiction Scale (SABAS) via an online platform. Pearson correlation coefficients assessed convergent/discriminant validity. Factor structure and measurement invariance were examined through confirmatory factor analysis (CFA) and multi-group CFA. Cronbach's alpha and McDonald's omega tested internal consistency. RESULTS: Associations between the ACSID-11 components and other scales supported convergent validity (i.e., ACSID-11 gaming scale with IGDS9-SF [0.37 ≤ r ≤ 0.41]; social networks use scale with BSMAS [0.24 ≤ r ≤ 0.31]) and discriminant validity (i.e., online gambling scale with BSMAS [0.16 ≤ r ≤ 0.19] and with SABAS [0.11 ≤ r ≤ 0.13]). A four-factor solution indicated good fit with comparative fit index (CFI) ranging from 0.982 to 0.958. The ACSID-11 was measurement invariant across sexes (∆CFI = -0.001 to 0.000) and different levels of related addictive behaviors (∆CFI = -0.001 to 0.000). Both Cronbach's alpha and McDonald's omega (0.63 to 0.97) were acceptable for both frequency and intensity of responses. CONCLUSIONS: The ACSID-11 is an appropriate scale to assess different kinds of PUI among Chinese adolescents and students. Psychometric assessment of the measure in other cultures and among clinical samples is recommended.

Habitat quality evaluation and pattern simulation of coastal salt marsh wetlands.

Coastal salt marsh wetlands not only sequester a large amount of organic carbon, mitigating the effect of climate change, but also nurture rich wetland resources and diverse ecological environments. In this study, habitat pattern and quality of the Jiangsu Yancheng Wetland Rare Birds National Nature Reserve were studied. The evolution of habitat patterns was analyzed using the U-Net model and Sentinel-2 data. The habitat quality was evaluated using the InVEST model, while the future habitat pattern in 2027 under different scenarios were simulated using the PLUS model. Our results showed that, during 2017-2022, the Suaeda salsa habitat showed a net decrease in area of 2077.61 ha, while Spartina alterniflora and Phragmites australis habitats manifested a net increase in different degrees. The overall habitat pattern was characterized by fragmentation decline and regularization enhancement. The habitat quality decreased from 0.75 to 0.72, mainly due to the loss of the S. salsa habitat and the expansion of the P. australis habitat. The simulation results indicated that, the habitat quality is expected to further decline to 0.71 under the natural development scenario, and 390.27 ha of S. salsa habitat will convert to P. australis. While in government control scenario, the habitat quality is expected to improve to 0.78, which was 0.07 higher than that in natural development scenario, and S. salsa habitat can be restored well. This study provides a scientific basis for the protection of suitable habitats for waterfowl and is crucial for the ecological conservation and management planning of nature reserves and coastal salt marsh wetlands.

Sub-micron pixel polarization-sensitive photodetector based on silicon nanowire.

Silicon nanowire is a potential candidate to be used as polarization-sensitive material, but the relative mechanism of polarization response must be carried out. Herein, a sub-micron metal-single silicon nanowire-metal photodetector exhibits polarization-sensitive characteristics with an anisotropic photocurrent ratio of 1.59 at 780 nm, an excellent responsivity of 24.58 mA/W, and a high detectivity of 8.88 × 109 Jones at 980 nm. The underlying principle of optical anisotropy in silicon nanowire is attributed to resonance enhancement verified by polarizing light microscopy and simulation. Furthermore, Stokes parameter measurements and imaging are all demonstrated by detecting the characteristics of linearly polarized light and imaging the polarizer array, respectively. Given the maturity of silicon processing, the sub-micron linearly polarized light detection proposed in this study lays the groundwork for achieving highly integrated, simplified processes, and cost-effective on-chip polarization-sensitive optical chips in the future.

DNA response element-based smart drug delivery systems for precise drug release.

Smart drug delivery systems (DDSs) that respond to, interact with, or are actuated by biological signals or pathological abnormalities (e.g., the tumor microenvironment) for controllable drug release are appealing therapeutic platforms for cancer treatment. Owing to their inherent self-assembled nature, nucleic acids have emerged as programmable materials for the development of multifunctional structures. In response to external environmental stimuli, DNA response elements can serve as switches to trigger conformational changes in DNA structures. Their stimulus-responsive properties make them promising candidates for constructing smart DDSs, and advancements in DNA response element-based DDSs in the field of biomedicine have been made. This review summarizes different types of DNA response elements, including DNA aptamers, DNAzymes, disulfide bond-modified DNA, pH-responsive DNA motifs, and photocleavable DNA building blocks, and highlights the advancements in DNA response element-based smart DDSs for precise drug release. Finally, future challenges and perspectives in this field are discussed.

Regulation of candidalysin underlies Candida albicans persistence in intravascular catheters by modulating NETosis.

Candida albicans is a leading cause of intravascular catheter-related infections. The capacity for biofilm formation has been proposed to contribute to the persistence of this fungal pathogen on catheter surfaces. While efforts have been devoted to identifying microbial factors that modulate C. albicans biofilm formation in vitro, our understanding of the host factors that may shape C. albicans persistence in intravascular catheters is lacking. Here, we used multiphoton microscopy to characterize biofilms in intravascular catheters removed from candidiasis patients. We demonstrated that, NETosis, a type of neutrophil cell death with antimicrobial activity, was implicated in the interaction of immune cells with C. albicans in the catheters. The catheter isolates exhibited reduced filamentation and candidalysin gene expression, specifically in the total parenteral nutrition culture environment. Furthermore, we showed that the ablation of candidalysin expression in C. albicans reduced NETosis and conferred resistance to neutrophil-mediated fungal biofilm elimination. Our findings illustrate the role of neutrophil NETosis in modulating C. albicans biofilm persistence in an intravascular catheter, highlighting that C. albicans can benefit from reduced virulence expression to promote its persistence in an intravascular catheter.

A preliminary study of the effectiveness of video visitation on depression and stress in mothers with preterm infants during the pandemic.

BACKGROUND AND PURPOSE: Parents of preterm infants experience anxiety and stress in the neonatal intensive care unit (NICU). Visitation restrictions due to COVID-19 have increased maternal pressure and limited bonding opportunities. Little research exists in Taiwan on using video conferencing as a solution. This study investigates depression and stress levels in mothers of preterm infants and evaluates the effectiveness of video visitation during NICU restrictions. METHODS: This study adopts a cross-sectional design and a qualitative survey. Mothers of premature infants were recruited and they participated in the study. Interventions for video visits were scheduled on the third day of admission to the NICU (T1) and during the second week of the study (T2). After each video visit, participants completed an online survey. The study's online survey used structured questionnaires including demographics, the Edinburgh Postnatal Depression Scale (EPDS) and the Parental Stress Scale (PSS): Infant Hospitalization (IH). RESULTS: A total of 51 mothers of preterm infants participated in the study. During the T1 and T2 periods, single mothers with lower educational levels and those aged below 30 experienced depression and high levels of stress. Lower birth weight and gestational age were associated with maternal depression. Video visitation intervention led to a significant decrease in depression scores (EPDS, T1: 11.3 ± 5.5 vs. T2: 10.1 ± 5.2, p = 0.039). Positive correlations were observed between EPDS and PSS: IH scores (p < 0 .005). CONCLUSION: Video visitation intervention can reduce maternal depression in mothers with preterm infants. Since it is practical, video visitation may be applied even after the pandemic.

Berberine ameliorates chronic intermittent hypoxia-induced cardiac remodelling by preserving mitochondrial function, role of SIRT6 signalling.

Chronic intermittent hypoxia (CIH) is associated with an increased risk of cardiovascular diseases. Previously, we have shown that berberine (BBR) is a potential cardioprotective agent. However, its effect and mechanism on CIH-induced cardiomyopathy remain uncovered. This study was designed to determine the effects of BBR against CIH-induced cardiac damage and to explore the molecular mechanisms. Mice were exposed to 5 weeks of CIH with or without the treatment of BBR and adeno-associated virus 9 (AAV9) carrying SIRT6 or SIRT6-specific short hairpin RNA. The effect of BBR was evaluated by echocardiography, histological analysis and western blot analysis. CIH caused the inactivation of myocardial SIRT6 and AMPK-FOXO3a signalling. BBR dose-dependently ameliorated cardiac injury in CIH-induced mice, as evidenced by increased cardiac function and decreased fibrosis. Notably, SIRT6 overexpression mimicked these beneficial effects, whereas infection with recombinant AAV9 carrying SIRT6-specific short hairpin RNA abrogated them. Mechanistically, BBR reduced oxidative stress damage and preserved mitochondrial function via activating SIRT6-AMPK-FOXO3a signalling, enhancing mitochondrial biogenesis as well as PINK1-Parkin-mediated mitophagy. Taken together, these data demonstrate that SIRT6 activation protects against the pathogenesis of CIH-induced cardiac dysfunction. BBR attenuates CIH-induced myocardial injury by improving mitochondrial biogenesis and PINK1-Parkin-dependent mitophagy via the SIRT6-AMPK-FOXO3a signalling pathway.

Bioinspired super-hydrophilic zwitterionic polymer armor combats thrombosis and infection of vascular catheters.

Thrombosis and infection are two major complications associated with central venous catheters (CVCs), which significantly contribute to morbidity and mortality. Antifouling coating strategies currently represent an efficient approach for addressing such complications. However, existing antifouling coatings have limitations in terms of both duration and effectiveness. Herein, we propose a durable zwitterionic polymer armor for catheters. This armor is realized by pre-coating with a robust phenol-polyamine film inspired by insect sclerotization, followed by grafting of poly-2-methacryloyloxyethyl phosphorylcholine (pMPC) via in-situ radical polymerization. The resulting pMPC coating armor exhibits super-hydrophilicity, thereby forming a highly hydrated shell that effectively prevents bacterial adhesion and inhibits the adsorption and activation of fibrinogen and platelets in vitro. In practical applications, the armored catheters significantly reduced inflammation and prevented biofilm formation in a rat subcutaneous infection model, as well as inhibited thrombus formation in a rabbit jugular vein model. Overall, our robust zwitterionic polymer coating presents a promising solution for reducing infections and thrombosis associated with vascular catheters.

A Rare Case of Sigmoid Colon Perforation in a Patient With Severe Acute Pancreatitis.

Severe acute pancreatitis can cause systemic inflammation and multiorgan failure. We present the case of a 60-year-old woman who presented with necrotizing pancreatitis and subsequently developed a sigmoid colon perforation. The perforation presumably occurred because of extravasation of pancreatic enzymes into the abdominal cavity, resulting in colonic wall injury. Our case highlights the rare colonic complications of severe acute pancreatitis.

MMP-9 upregulation may predict hemorrhagic transformation after endovascular thrombectomy.

Background: Hemorrhagic transformation (HT) is a serious complication after endovascular thrombectomy (EVT) for patients with acute ischemic stroke (AIS). We analyzed the plasma levels of MMP-9 before and after EVT and assessed the temporal changes of MMP-9 that may be associated with, and therefore predict, HT after EVT. Methods: We enrolled 30 AIS patients who received EVT, and 16 (53.3%) developed HT. The levels of MMP-9 in plasma collected from the arteries of AIS patients before and immediately after EVT were measured using ELISA. The percent change in MMP-9 after EVT (after/before) was calculated and compared between patients with and without HT. Results: The median age of the AIS patients was 70 years, and 13 patients (43.3%) were men. The median National Institutes of Health Stroke Scale (NIHSS) scores of patients with HT were 18 on admission and 18 after EVT. The median NIHSS scores of patients without HT were 17 on admission and 11 after EVT. Patients with HT demonstrated significantly greater percentage increases in arterial MMP-9 levels after EVT. Conclusion: Patients with AIS who developed HT had significantly increased arterial MMP-9 levels after EVT, suggesting that the upregulation of MMP-9 following EVT could serve as a predictive biomarker for HT.

Hippocampal proteome comparison of infant and adult Fmr1 deficiency mice reveals adult-related changes associated with postsynaptic density.

Deficiency in fragile X mental retardation 1 (Fmr1) leads to loss of its encoded protein FMRP and causes fragile X syndrome (FXS) by dysregulating its target gene expression in an age-related fashion. Using comparative proteomic analysis, this study identified 105 differentially expressed proteins (DEPs) in the hippocampus of postnatal day 7 (P7) Fmr1-/y mice and 306 DEPs of P90 Fmr1-/y mice. We found that most DEPs in P90 hippocampus were not changed in P7 hippocampus upon FMRP absence, and some P90 DEPs exhibited diverse proteophenotypes with abnormal expression of protein isoform or allele variants. Bioinformatic analyses showed that the P7 DEPs were mainly enriched in fatty acid metabolism and oxidoreductase activity and nutrient responses; whereas the P90 PEPs (especially down-regulated DEPs) were primarily enriched in postsynaptic density (PSD), neuronal projection development and synaptic plasticity. Interestingly, 25 of 30 down-regulated PSD proteins present in the most enriched protein to protein interaction network, and 6 of them (ANK3, ATP2B2, DST, GRIN1, SHANK2 and SYNGAP1) are both FMRP targets and autism candidates. Therefore, this study suggests age-dependent alterations in hippocampal proteomes upon loss of FMRP that may be associated with the pathogenesis of FXS and its related disorders. SIGNIFICANCE: It is well known that loss of FMRP resulted from Fmr1 deficiency leads to fragile X syndrome (FXS), a common neurodevelopmental disorder accompanied by intellectual disability and autism spectrum disorder (ASD). FMRP exhibits distinctly spatiotemporal patterns in the hippocampus between early development and adulthood, which lead to distinct dysregulations of gene expression upon loss of FMRP at the two age stages potentially linked to age-related phenotypes. Therefore, comparison of hippocampal proteomes between infancy and adulthood is valuable to provide insights into the early causations and adult-dependent consequences for FXS and ASD. Using a comparative proteomic analysis, this study identified 105 and 306 differentially expressed proteins (DEPs) in the hippocampi of postnatal day 7 (P7) and P90 Fmr1-/y mice, respectively. Few overlapping DEPs were identified between P7 and P90 stages, and the P7 DEPs were mainly enriched in the regulation of fatty acid metabolism and oxidoreduction, whereas the P90 DEPs were preferentially enriched in the regulation of synaptic formation and plasticity. Particularly, the up-regulated P90 proteins are primarily involved in immune responses and neurodegeneration, and the down-regulated P90 proteins are associated with postsynaptic density, neuron projection and synaptic plasticity. Our findings suggest that distinctly changed proteins in FMRP-absence hippocampus between infancy and adulthood may contribute to age-dependent pathogenesis of FXS and ASD.

HLA-DQB1 Allele Polymorphism Associated with Oral Submucous Fibrosis in Hunan, China.

Methods: 44 OSF patients and 44 healthy volunteers were included in this study. To detect the expression frequency of HLA-DQB1 alleles in the two groups and analyze significant allelic subtypes and their relative risk, polymerase chain reaction (PCR) sequence-specific primers were used. Subsequently, based on the identification of differential genes, we compare the gene expression levels of OSF patients and healthy volunteers expressing differential genes by real-time quantitative PCR. Results: The expression frequency of the HLA-DQB1 ∗05 : 02 allele in the OSF group (36.4%) was significantly higher than in the controls (13.6%), and exposure to the HLA-DQB1 ∗05 : 02 allele was strongly related to OSF (OR (95% CI) = 3.619 (1.257,10.421), Wald χ2 = 5.681, P=0.017). However, there were no significant differences in the allele expression frequencies of DQB1 ∗02 : 01, DQB1 ∗03 : 03, DQB1 ∗05 : 01, DQB1 ∗05 : 03, DQB1 ∗06 : 02, DQB1 ∗06 : 03, and DQB1 ∗06 : 04 in the OSF group compared with the controls (all P > 0.05). Furthermore, the relative expression level of the HLA-DQB1 ∗05 : 02 allele in the OSF group (3.98 ± 3.50) was significantly higher than in controls (0.70 ± 0.41). Conclusions: There are differences in the HLA-DQB1 allele polymorphisms between the healthy population and patients with oral submucosal fibrosis. Preliminarily, it is suggested that the HLA-DQB1 ∗05 : 02 allele, which has a strong correlation with OSF and great differential expression between patients with OSF and controls, might be a susceptibility gene for OSF in Hunan.