Osteoporotic Precise Screening Using Chest Radiography and Artificial Neural Network: The OPSCAN Randomized Controlled Trial.

Background Diagnosing osteoporosis is challenging due to its often asymptomatic presentation, which highlights the importance of providing screening for high-risk populations. Purpose To evaluate the effectiveness of dual-energy x-ray absorptiometry (DXA) screening in high-risk patients with osteoporosis identified by an artificial intelligence (AI) model using chest radiographs. Materials and Methods This randomized controlled trial conducted at an academic medical center included participants 40 years of age or older who had undergone chest radiography between January and December 2022 without a history of DXA examination. High-risk participants identified with the AI-enabled chest radiographs were randomly allocated to either a screening group, which was offered fully reimbursed DXA examinations between January and June 2023, or a control group, which received usual care, defined as DXA examination by a physician or patient on their own initiative without AI intervention. A logistic regression was used to test the difference in the primary outcome, new-onset osteoporosis, between the screening and control groups. Results Of the 40 658 enrolled participants, 4912 (12.1%) were identified by the AI model as high risk, with 2456 assigned to the screening group (mean age, 71.8 years ± 11.5 [SD]; 1909 female) and 2456 assigned to the control group (mean age, 72.1 years ± 11.8; 1872 female). A total of 315 of 2456 (12.8%) participants in the screening group underwent fully reimbursed DXA, and 237 of 315 (75.2%) were identified with new-onset osteoporosis. After including DXA results by means of usual care in both screening and control groups, the screening group exhibited higher rates of osteoporosis detection (272 of 2456 [11.1%] vs 27 of 2456 [1.1%]; odds ratio [OR], 11.2 [95% CI: 7.5, 16.7]; P < .001) compared with the control group. The ORs of osteoporosis diagnosis were increased in screening group participants who did not meet formalized criteria for DXA compared with those who did (OR, 23.2 [95% CI: 10.2, 53.1] vs OR, 8.0 [95% CI: 5.0, 12.6]; interactive P = .03). Conclusion Providing DXA screening to a high-risk group identified with AI-enabled chest radiographs can effectively diagnose more patients with osteoporosis. Clinical trial registration no. NCT05721157 © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Smith and Rothenberg in this issue.

Optimization of the tandem enzyme activity of V-MOF and its derivatives for highly sensitive nonenzymatic detection of cholesterol in living cells.

It remains a great challenge to properly design and synthesize single-component artificial tandem enzymes for specific substrates with high selectivity. Herein, V-MOF is synthesized by solvothermal method and its derivatives are constructed via pyrolyzing V-MOF in nitrogen atmosphere at different temperatures, which are denoted as V-MOF-y (y = 300, 400, 500, 700 and 800). V-MOF and V-MOF-y possess tandem enzyme-like activity, i.e. cholesterol oxidase-like and peroxidase-like activity. Among them, V-MOF-700 shows the strongest tandem enzyme activity for V-N bonds. Based on the cascade enzyme activity of V-MOF-700, the nonenzymatic detection platform for cholesterol by fluorescent assay can be established in the presence of o-phenylenediamine (OPD) for the first time. The detection mechanism is that V-MOF-700 catalyzes cholesterol to generate hydrogen peroxide and further form hydroxyl radical (•OH), which can oxidize OPD to obtain oxidized OPD (oxOPD) with yellow fluorescence. The linear detection of cholesterol ranges of 2-70 µM and 70-160 µM with a lower detection limit of 0.38 µM (S/N = 3) are obtained. This method is used to detect cholesterol in human serum successfully. Especially, it can be applied to the rough quantification of membrane cholesterol in living tumor cells, indicating that it has the potential for clinical application.

Detrimental Association Between Blood Cadmium Concentration and Trabecular Bone Score.

Osteoporosis has been recognized as a significant cause of disability in the elderly leading to heavy socioeconomic burden. Current measurements such as dual-energy X-ray absorptiometry (DEXA) and bone mineral density (BMD) have limitations. In contrast, trabecular bone score (TBS) is an emerging tool for bone quality assessment. The objective of our study was to investigate the relationship between TBS and trace elements (cadmium and lead). We analyzed all subjects from the 2005-2006 and 2007-2008 National Health and Nutrition Examination Survey (NHANES) dataset and included a total of 8,244 participants in our study; 49.4% of the enrolled subjects were male. We used blood cadmium (Cd) and lead (Pb) concentrations to define environmental exposure. The main variables were TBS and BMD. Other significant demographic features were included as covariates and later adjusted using linear regression models to determine the association between TBS and four quartiles based on the blood trace element concentrations with or without sex differences. The fully adjusted regression model revealed a negative relationship between TBS and blood cadmium (B-Cd) significant for both males and females (both p < 0.05). The ß-coefficient for males was -0.009 (95% confidence intervals (CI): (-0.015 to -0.004)) and -0.019 for female (95% CI: (-0.024 to -0.013)). We also found a dose-dependent relationship between TBS and B-Cd for both sexes (both trend's p < 0.05). Our study concluded that TBS could measure Cd-related bone quality deterioration for both males and females.

Generation of dual-supercontinuum coherent radiation in acetone mixed with carbon disulfide by stimulated Raman scattering.

Stimulated Raman scattering (SRS) in a liquid has been a major focus of nonlinear optics. Traditional SRS generates single or cascaded Stokes components arising from spontaneous Raman noise. Herein, we report the formation mechanism of a specific spectrum-continuous spectroscopy technique based on SRS of mixed liquids. SRS of a mixed acetone and carbon disulfide solution is investigated by a pulsed Nd:YAG laser with a wavelength of 532 nm. Two remarkably asymmetric broadened SRS lines are obtained. When the volume ratio is 7:3, the broadened spectral bands are optimized. The supercontinuum spectroscopy phenomenon is explained by hydrogen bond formation, adjacent vibrational modes coupling, and laser-induced plasma generation. This technique has the potential to contribute to the development of a supercontinuum Raman laser.

Periodontitis, Helicobacter pylori infection, and gastrointestinal tract cancer mortality.

AIM: Periodontitis has been proposed to lead to Helicobacter pylori infection, which could cause many gastrointestinal tract cancers. This study aimed to determine the association or otherwise between periodontitis and survival outcomes in individuals with respect to H. pylori infection. MATERIALS AND METHODS: The study population comprised 4955 subjects aged 20-90 who had received both periodontal examination and H. pylori serum test in the Third National Health and Nutrition Examination Survey (NHANES III) database. Logistic regression models were used to analyse the association between periodontitis and H. pylori seropositivity (H. pylori infection). Survival analysis was performed using the NHANES III linked to mortality data. Cox proportional hazard regression was carried out to investigate the association between periodontitis and gastrointestinal tract cancer mortality in individuals with/without H. pylori infection. RESULTS: Compared to periodontal health, periodontitis was significantly associated with increased odds of H. pylori infection (OR = 1.271, 95% CI = 1.177-1.372). Periodontitis significantly increased the mortality risk from all causes (HR = 1.574, 95% CI = 1.327-1.866) and all cancers (HR = 1.948, 95% CI = 1.701-2.232), including gastrointestinal (GI) tract cancer (HR = 4.140, 95% CI = 3.656-4.687), gastric cancer (HR = 4.288, 95% CI = 3.969-4.632), and colorectal cancer (HR = 4.814, 95% CI = 3.849-6.020) in subjects with H. pylori infection after adjusting for health-related factors. Periodontitis was significantly related to the decreased survival time in subjects with GI tract (p = .001) or colorectal cancer (p = .002) and H. pylori infection. CONCLUSION: Our study demonstrated that periodontitis was significantly associated with higher mortality risk of GI tract, gastric, and colorectal cancer in subjects with H. pylori infection. Owing to an interactive effect between periodontitis and H. pylori infection on cancer mortality, H. pylori infection has a significant moderating effect in regulating the association between periodontitis and mortality due to all cancers, including GI tract cancer and colorectal cancer.

The Polymorphism at PLCB4 Promoter (rs6086746) Changes the Binding Affinity of RUNX2 and Affects Osteoporosis Susceptibility: An Analysis of Bioinformatics-Based Case-Control Study and Functional Validation.

Purpose: Genome-wide association studies have identified numerous genetic variants that are associated with osteoporosis risk; however, most of them are present in the non-coding regions of the genome and the functional mechanisms are unknown. In this study, we aimed to investigate the potential variation in runt domain transcription factor 2 (RUNX2), which is an osteoblast-specific transcription factor that normally stimulates bone formation and osteoblast differentiation, regarding variants within RUNX2 binding sites and risk of osteoporosis in postmenopausal osteoporosis (PMOP). Methods: We performed bioinformatics-based prediction by combining whole genome sequencing and chromatin immunoprecipitation sequencing to screen functional SNPs in the RUNX2 binding site using data from the database of Taiwan Biobank; Case-control studies with 651 postmenopausal women comprising 107 osteoporosis patients, 290 osteopenia patients, and 254 controls at Tri-Service General Hospital between 2015 and 2019 were included. The subjects were examined for bone mass density and classified into normal and those with osteopenia or osteoporosis by T-scoring with dual-energy X-ray absorptiometry. Furthermore, mRNA expression and luciferase reporter assay were used to provide additional evidence regarding the associations identified in the association analyses. Chi-square tests and logistic regression were mainly used for statistical assessment. Results: Through candidate gene approaches, 3 SNPs in the RUNX2 binding site were selected. A novel SNP rs6086746 in the PLCB4 promoter was identified to be associated with osteoporosis in Chinese populations. Patients with AA allele had higher risk of osteoporosis than those with GG+AG (adjusted OR = 6.89; 95% confidence intervals: 2.23-21.31, p = 0.001). Moreover, the AA genotype exhibited lower bone mass density (p < 0.05). Regarding mRNA expression, there were large differences in the correlation between PLCB4 and different RUNX2 alleles (Cohen's q = 0.91). Functionally, the rs6086746 A allele reduces the RUNX2 binding affinity, thus enhancing the suppression of PLCB4 expression (p < 0.05). Conclusions: Our results provide further evidence to support the important role of the SNP rs6086746 in the etiology of osteopenia/osteoporosis, thereby enhancing the current understanding of the susceptibility to osteoporosis. We further studied the mechanism underlying osteoporosis regulation by PLCB4.

Intramolecular Vibration Energy-Transfer-Driven Cascaded Stimulated Raman Scattering and Four-Wave Mixing in Benzene Series.

Cascaded stimulated Raman scattering (SRS) of benzene, bromobenzene, chlorobenzene, ethylbenzene, and toluene was investigated by a pulsed Nd:YAG laser with 532 nm wavelength. The results showed that the third-order Stokes SRS of the ring skeleton vibration (CC at 3006 cm-1) accompanied by another higher-frequency Stokes SRS of the CH stretching vibration (at 3066 cm-1), which arose only when the third-order Stokes SRS of the ring skeleton was produced, can be attributed to the vibration energy transfer between vibration energy levels of CC and CH. The Stokes and anti-Stokes SRS rings, which originated from the intramolecular energy-transfer-enhanced four-wave mixing (FWM) processes, can be observed only in the forward direction along different angles apart from the pump beam direction. The phenomenon also existed in other derivatives of benzene. We propose the intramolecular energy-transfer-enhanced SRS for the first time, which can be used for a broadband Raman laser.

Study of hydrogen bonding interactions in ethylene glycol-water binary solutions by Raman spectroscopy.

EG (ethylene glycol) is a good model system for the study of the fundamental hydrogen bonds in aqueous solutions. Using Raman spectroscopy, we have investigated the EG volume fraction induced variation in the hydrogen bonding interactions and conformations of EG-H2O (water) binary solutions. New hydrogen bonding networks is evidenced by the appearance of remarkable changes in Raman spectra and the full width at half maximum (FWHM) when the mixing volume ratio is 0.5. The H-bond in water molecules firstly strengthened and then weakened with the increasing concentration of EG. Meanwhile, the dominant association structure also changed from H2O-H2O to EG-H2O in binary solutions in this process. We provide a simple but effective method for studying EG-H2O binary solutions. It also has exciting potential prospects and can be easily extended to other mixing situations.

The Decisive Case-Control Study Elaborates the Null Association between ESR1 XbaI and Osteoarthritis in Asians: A Case-Control Study and Meta-Analysis.

(1) Background: The prevalence of knee osteoarthritis (OA) in women is significantly higher than in men. The estrogen receptor α (ERα) has been considered to play a key role due to a large gender difference in its expression. ERα is encoded by the gene estrogen receptor 1 (ESR1), which is widely studied to explore the gender difference in knee OA. Several polymorphisms in ESR1 [PvuII (rs2234693) and BtgI (rs2228480)] were confirmed as the risk factors of OA. However, the evidence of the last widely investigated polymorphism, ESR1 Xbal (rs9340799), is still insufficient for concluding its effect on knee OA. (2) Objective: This study proposed a case-control study to investigate the association between ESR1 Xbal and knee OA. Moreover, a meta-analysis and trial sequential analysis (TSA) were conducted to enlarge the sample size for obtaining a conclusive evidence. (3) Methods: In total, 497 knee OA cases and 473 healthy controls were recruited between March 2015 and July 2018. The Kellgren-Lawrence grading system was used to identify the knee OA cases. To improve the evidence level of our study, we conducted a meta-analysis including the related studies published up until December 2018 from PubMed, Embase, and previous meta-analysis. The results are expressed as odds ratios (ORs) with corresponding 95% confidence intervals (CI) for evaluating the effect of this polymorphism on knee OA risk. TSA was used to estimate the sample sizes required in this issue. (4) Results: We found non-significant association between the G allele and knee OA [Crude-OR: 0.97 (95% CI: 0.78-1.20) and adjusted-OR: 0.90 (95% CI: 0.71-1.15) in allele model] in the present case-control study, and the analysis of other genetic models showed a similar trend. After including six published studies and our case-control studies, the current evidence with 3174 Asians showed the conclusively null association between ESR1 XbaI and knee OA [OR: 0.78 (95% CI: 0.59-1.04)] with a high heterogeneity (I2: 78%). The result of Caucasians also concluded the null association [OR: 1.05 (95% CI: 0.56-1.95), I2: 87%]. (5) Conclusions: The association between ESR1 XbaI and knee OA was not similar with other polymorphisms in ESR1, which is not a causal relationship. This study integrated all current evidence to elaborate this conclusion for suggesting no necessity of future studies.

p5 Peptide-Loaded Human Adipose-Derived Mesenchymal Stem Cells Promote Neurological Recovery After Focal Cerebral Ischemia in a Rat Model.

Adipose-derived mesenchymal stem cells markedly attenuated brain infarct size and improved neurological function in rats. The mechanisms for neuronal cell death have previously been defined in stress states to suggest that an influx of calcium ions into the neurons activates calpain cleavage of p35 into p25 forming a hyperactive complex that induces cell death. Now we report that p5, a 24-residue peptide derived from p35, offers protection to neurons and endothelial cells in vitro. In vivo administration of human adipose-derived mesenchymal stem cells (hADMSCs) loaded with this therapeutic peptide to post-stroke rats had no effect on the infarct volume. Nevertheless, the treatment led to improvement in functional recovery in spatial learning and memory (water maze), bilateral coordination and sensorimotor function (rotating pole), and asymmetry of forelimb usage (cylinder test). However, the treatment may not impact on cutaneous sensitivity (adhesive tape removal test). In addition, the double immunofluorescence with human cell-specific antibodies revealed that the number of surviving transplanted cells was higher in the peri-infarcted area of animals treated with hADMSCs + P5 than that in hADMSC-treated or control animals, concomitant with reduced number of phagocytic, annexin3-positive cells in the peri-infarcted region. However, the combination therapy did not increase the vascular density in the peri-infarcted area after stroke. In conclusion, administration of hADMSC-loaded p5 peptide to post-stroke rats created conditions that supported survival of drug-loaded hADMSCs after cerebral ischemia, suggesting its therapeutic potential in patients with stroke.

A Hematologist-Level Deep Learning Algorithm (BMSNet) for Assessing the Morphologies of Single Nuclear Balls in Bone Marrow Smears: Algorithm Development.

BACKGROUND: Bone marrow aspiration and biopsy remain the gold standard for the diagnosis of hematological diseases despite the development of flow cytometry (FCM) and molecular and gene analyses. However, the interpretation of the results is laborious and operator dependent. Furthermore, the obtained results exhibit inter- and intravariations among specialists. Therefore, it is important to develop a more objective and automated analysis system. Several deep learning models have been developed and applied in medical image analysis but not in the field of hematological histology, especially for bone marrow smear applications. OBJECTIVE: The aim of this study was to develop a deep learning model (BMSNet) for assisting hematologists in the interpretation of bone marrow smears for faster diagnosis and disease monitoring. METHODS: From January 1, 2016, to December 31, 2018, 122 bone marrow smears were photographed and divided into a development cohort (N=42), a validation cohort (N=70), and a competition cohort (N=10). The development cohort included 17,319 annotated cells from 291 high-resolution photos. In total, 20 photos were taken for each patient in the validation cohort and the competition cohort. This study included eight annotation categories: erythroid, blasts, myeloid, lymphoid, plasma cells, monocyte, megakaryocyte, and unable to identify. BMSNet is a convolutional neural network with the YOLO v3 architecture, which detects and classifies single cells in a single model. Six visiting staff members participated in a human-machine competition, and the results from the FCM were regarded as the ground truth. RESULTS: In the development cohort, according to 6-fold cross-validation, the average precision of the bounding box prediction without consideration of the classification is 67.4%. After removing the bounding box prediction error, the precision and recall of BMSNet were similar to those of the hematologists in most categories. In detecting more than 5% of blasts in the validation cohort, the area under the curve (AUC) of BMSNet (0.948) was higher than the AUC of the hematologists (0.929) but lower than the AUC of the pathologists (0.985). In detecting more than 20% of blasts, the AUCs of the hematologists (0.981) and pathologists (0.980) were similar and were higher than the AUC of BMSNet (0.942). Further analysis showed that the performance difference could be attributed to the myelodysplastic syndrome cases. In the competition cohort, the mean value of the correlations between BMSNet and FCM was 0.960, and the mean values of the correlations between the visiting staff and FCM ranged between 0.952 and 0.990. CONCLUSIONS: Our deep learning model can assist hematologists in interpreting bone marrow smears by facilitating and accelerating the detection of hematopoietic cells. However, a detailed morphological interpretation still requires trained hematologists.

Dietary habits, lifestyle factors and neurodegenerative diseases.

Worldwide stroke is increasing in parallel with modernization, changes in lifestyle, and the growing elderly population. Our review is focused on the link between diet, as part of 'modern lifestyle', and health in the context of genetic predisposition of individuals to 'unhealthy' metabolic pathway activity. It is concluded that lifestyle including high sugar diets, alcohol and tobacco addiction or high fat diets as well as ageing, brain injury, oxidative stress and neuroinflammation, negatively influence the onset, severity and duration of neurodegenerative diseases. Fortunately, there are several healthy dietary components such as polyunsaturated fatty acids and the anti-oxidants curcumin, resveratrol, blueberry polyphenols, sulphoraphane, salvionic acid as well as caloric restriction and physical activity, which may counteract ageing and associated neurodegenerative diseases via increased autophagy or increased neurogenesis in the adult brain.

Nitrogen-doped carbon dots-V2O5 nanobelts sensing platform for sensitive detection of ascorbic acid and alkaline phosphatase activity.

In this work, the as-prepared V2O5 nanobelts can sensitively quench the fluorescence of nitrogen-doped carbon dots (N-CDs) based on the inner filter effect (IFE). In the presence of ascorbic acid (AA), the fluorescence of N-CDs can recover through the redox reaction between V2O5 nanobelts and AA. Meanwhile, in the presence of both alkaline phosphatase (ALP) and ascorbyl-2-phosphate (AAP), the fluorescence of N-CDs can also restore since AAP can be hydrolyzed into AA by ALP. Under optimum conditions, the linear range for AA is from 0.01 to 2.5 µM with a detection limit of 3 nM and that for ALP is from 0.1 to 30 U/L with a detection limit of 0.04 U/L (S/N = 3). Particularly, the proposed probe could be successfully used to detect AA and ALP in human serum samples. Furthermore, N-CDs can be applied in fluorescence imaging of Human breast cancer cells with satisfactory results.

The protective effect of syringic acid on dextran sulfate sodium-induced experimental colitis in BALB/c mice.

Inflammatory bowel diseases involve chronic intestinal inflammation which is mostly caused by Crohn's disease and ulcerative colitis (UC) conditions. Patients having UC are prone to colorectal cancer and dysplastic polyps, and also have sporadic adenomas. Syringic acid (SA) possesses many health benefits including antioxidant, anti-bacterial, and anti-cancer. This study was aimed to identify the effects of SA on UC, using a murine experimental model. Clinical symptoms and weight loss were significantly reduced in mice induced with dextran sulfate sodium (DSS) and treated with SA, compared to untreated mice. The effects of SA exhibited in DSS-induced mice were associated with significant decrease in the expressions levels of inflammatory mediators such as inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), pro-inflammatory cytokines (tumor necrosis factor [TNF-α], interleukin [IL-1ß and IL-6]), remarkable amelioration of colonic architectural disruption, and a significant reduction in the activity of colonic myeloperoxidase. To further confirm the anti-inflammatory property of SA, RAW 264.7 cells were stimulated with lipopolysaccharides. SA dose-dependently inhibited the cytokines TNF-α, IL-1ß, and IL-6. It also decreased the expressions of p65-NF-κB and IκB, thus reducing the activation and nuclear accumulation of p-STAT-3Y705 . This prohibited the degradation of inhibitory protein, IκB, as well as inhibited the nuclear translocation of p65-NF-κB in colonic tissue. It was concluded that SA has a potential to limit inflammation via inhibiting the p65-NF-κB and STAT3 signaling; hence it can be used for therapeutic purposes.

Hypertension control and risk of colonic diverticulosis.

BACKGROUND: The prevalence of diverticulosis has increased in our aging population, but the risk factors for diverticulosis are not fully understood. The role of hypertension in the risk of diverticulosis remains uncertain. This study investigated whether hypertension is associated with asymptomatic colorectal diverticulosis. METHODS: This study enrolled asymptomatic patients who received a colonoscopy as part of a health check. Hypertension was defined by actual measured blood pressure. Logistic regression models were used to examine the relationship between hypertension and diverticulosis. In addition, we established three logistic regression models for covariate adjustment, and further stratified patients with hypertension into three subgroups based on their type of hypertension. RESULTS: The study group consisted of 2748 participants, including 141 participants with diverticulosis and 2607 participants without diverticulosis. After adjustments for potential covariates, the odds ratio (OR) for having diverticulosis was 1.83 (95% confidence interval, 1.21-2.75, p = 0.004) in the hypertension group compared with the group without hypertension. In subgroup analyses, hypertension without antihypertensive medication use, and hypertension despite the use of antihypertensive medication were also significantly associated with the occurrence of asymptomatic diverticulosis (OR = 1.73, p = 0.028; OR = 2.07, p = 0.013, respectively). Current normal blood pressure under antihypertensive drug therapy was not associated with diverticulosis (OR = 1.74, p = 0.092). CONCLUSIONS: Our findings suggest a positive association between hypertension and diverticulosis. Participants with poorly controlled blood pressure were found to have a higher risk of asymptomatic diverticulosis. Our study presents epidemiologic evidence for future prevention strategies against diverticulosis.

Using an extended theory of planned behaviour to predict smoking cessation counsellors' intentions to offer smoking cessation support in the Taiwanese military: a cross-sectional study.

OBJECTIVES: To use the extended theory of planned behaviour (TPB) to predict smoking cessation counsellors' intentions to offer smoking cessation support. DESIGN: Cross-sectional study SETTING: Taiwanese military PARTICIPANTS: A survey of 432 smoking cessation counsellors was conducted in 2017. PRIMARY AND SECONDARY OUTCOME MEASURES: All participants completed a self-administered questionnaire that solicited information concerning demographics, smoking behaviour, self-rated suitability for being a counsellor, the knowledge and skills learnt from training courses and the TPB construct. RESULTS: The factors of perceived behavioural control (ß=0.590, p<0.001), self-rated suitability for being a counsellor (acceptable vs not suitable, ß=0.436, p=0.001; suitable vs not suitable, ß=0.510, p<0.001), knowledge (ß=0.298, p=0.020) and professional specialty (military doctor vs non-military doctor, ß=0.198, p=0.034) were found to be correlated with intention. However, attitude, subjective norms and descriptive norms were determined to be non-significant correlates. The model explained 59.7% of the variance for the intention to offer smoking cessation support (F[12,343]=44.864, p<0.001). CONCLUSIONS: To encourage smoking cessation counsellors to offer cessation support to smokers, policies should aim to increase their perceived behavioural control, knowledge and self-rated suitability for being a counsellor.

Age-specific associations among functional COMT Val158Met polymorphism, resting parasympathetic nervous control and generalized anxiety disorder.

The functional Val158Met polymorphism (rs4680) of the Catechol-O-Methyltransferase (COMT) gene has been implicated in generalized anxiety disorder (GAD); however, the underlying neural mechanisms remain unexamined. Recent evidence reveals that low resting parasympathetic (vagal) control is an endophenotypic predictor of anxiety, while the effect of COMT rs4680 differs at different ages. Thus, we examined whether the COMT Val158Met variant could increase the risk of GAD through decreased resting parasympathetic nervous control in an age-specific manner. COMT rs4680 polymorphism was genotyped in 1,655 Han Chinese adults (1,142 healthy subjects and 513 patients with GAD; age: 20-65). High-frequency power (HF) of heart rate variability (HRV) was used to measure resting state parasympathetic nervous regulation. Non-genetic factors, such as gender, smoking status, medication use and comorbidity conditions, were treated as covariates. After adjusting for relevant covariates, there was a significant age x COMT genotype interaction on resting HF of HRV. In younger adults, Met allele carriers had a significantly lower HF index; however, older adults exhibited the opposite pattern, with Val/Val homozygotes exhibiting decreased HF values. Moreover, reduced HF-HRV is associated with increased risk of GAD. Finally, pathway analysis revealed a significant indirect effect of COMT on the risk of GAD via reduced resting HF-HRV, in the aforementioned age-dependent manner. Our findings are the first to demonstrate that COMT Val158Met polymorphism is associated with risk of GAD via reduced resting parasympathetic nervous control, an age-specific risk pathway.

Nitrogen-doped-carbon-coated hexagonal cobalt oxyhydroxide/reduced graphene oxide nanocomposite for sensitive and selective detection of nitrite in human hepatoma cells.

Selective and sensitive determination of nitrite is of great importance in practical application. In the present work, a novel nitrite sensing platform was built based on the fabrication of nitrogen-doped-carbon-coated hexagonal cobalt oxyhydroxide (CN@CoOOH) on reduced graphene oxide (RGO) using zeolitic imidazolate framework (ZIF)-67 as a precursor. The CN@CoOOH/RGO nanocomposite was confirmed by UV-visible spectroscopy, Fourier transform infrared spectroscopy, x-ray photoelectron spectrum, transmission electron microscopy, scanning electron microscopy, and x-ray diffraction. We applied the nanocomposite to detect nitrite selectively and sensitively through amperometry for the first time. The anodic current values increased with the addition of nitrite. Therefore, the concentrations of nitrite were quantitatively detected using a CN@CoOOH/RGO based sensor. A wider linear range of 0.1 to 7000 µM was obtained with a lower detection limit of 10 nM (S/N = 3). The proposed method was also applied to detect nitrite released from normal liver cells and human hepatoma cells.

In situ sulfur-doped graphitic carbon nitride nanosheets with enhanced electrogenerated chemiluminescence used for sensitive and selective sensing of l-cysteine.

In this study, in situ sulfur-doped carbon nitride nanosheets (S-g-C3N4 NSs) are used as the signal readout for the sensitive and selective sensing of l-cysteine (l-Cys) in human serum samples based on the competitive coordination chemistry of Cu2+ between l-Cys and S-g-C3N4 NSs. S-g-C3N4 NSs are prepared by using trithiocyanuric acid as a precursor for the first time, which exhibits stronger electrogenerated chemiluminescence (ECL) intensity compared with pristine graphitic carbon nitride nanosheets (g-C3N4 NSs). The ECL signals of the S-g-C3N4 NSs can be quenched by Cu2+ and the subsequent presence of l-Cys can recover the ECL signals of the S-g-C3N4 NSs. These changes are ascribed to the higher coordination ability between Cu2+ and l-Cys than that between Cu2+ and the S-g-C3N4 NSs. On the basis of this, the concentration of l-Cys can be quantitatively determined. Under optimized conditions, the ECL intensity recovery shows a linear relationship with the l-Cys concentration range from 30 nM to 0.2 mM with a lower detection limit of 5 nM (S/N = 3). The proposed method is highly sensitive and selective and is thus particularly useful for fast and simple clinical diagnosis of diseases, such as Alzheimer's disease and cardiovascular disease.

p17 from HIV induces brain endothelial cell angiogenesis through EGFR-1-mediated cell signalling activation.

HIV-associated neurocognitive disorder in HIV patients substantially reduces their quality of life. We previously showed that the HIV matrix protein, p17 could stimulate lymph-angiogenesis in vitro potentially contributing to lymphoma tumour growth and in addition is associated with vascular activation in neuro-degenerating brain tissue; here, therefore, we have investigated the detailed molecular mechanisms of this action. We performed in vitro cell culture, angiogenesis experiments, phospho-protein microarrays and Western blotting to identify cellular signalling induced by p17 within human brain endothelial cells (HbMEC), and inhibitor studies to block p17-induced vascular growth. We also characterised the effects of hippocampal CA1 injection of p17 on epidermal growth factor receptor-1 (EGFR1) expression linked to our murine model of dementia. p17 strongly induced angiogenesis of HbMEC (migration, tube formation and spheroid growth). p17 concomitantly increased phosphorylation of EGFR1 as well as down-stream intermediates ERK1/2, FAK, PLC-γ and PKC-ß whilst an inhibitor peptide of EGFR, blocked cell signalling and angiogenesis. Finally, Mice that showed reduced cognitive function and behavioural deficiencies after p17 injection, demonstrated that p17 localised in cortical microvessels and also neurones many of which stained positive for p-EGFR1 by histology/IHC. This work provides strong support that p17 may be involved in initiating and/or perpetuating vascular tissue pathophysiology associated with comorbidity in HIV patients.