Spatiotemporal variations in cardiovascular disease mortality in China from 1991 to 2009.

BACKGROUND: In China, the spatiotemporal variations in cardiovascular disease (CVD) mortality are seldom characterized to understand their epidemiological features. It would be helpful to evaluate the performance of CVD-related interventions for subsequent adjustments. METHODS: The 2010 Census data as well as the coronary heart disease (CHD) and stroke mortality data from the Disease Surveillance Points (DSPs) were used to calculate the age standardized death rates (ASDRs) of CVD in the DSP counties during 1991-1995, 1996-2000, 2004-2005, and 2006-2009. The ordinary kriging (OK) method was used to estimate the county-level death rates of CHD and stroke and achieved satisfactory results. RESULTS: The goodness-of-fit between measured and estimated values of CVD mortality was significant at the 0.01 level (0.34 < R2 < 0.98). The counties with high CHD death rates (> 75 per 105) were located in the Northwest, North, and Northeast in 1991-2000 and then extended toward the North, Central, and South, yielding an inverted-triangle-shaped area in 2004-2009. The counties with a CHD death rate increase greater than 100% were concentrated in the Northeast and South. The Northeast-Southwest regions with a high stroke death rate gradient (> 150 per 105) narrowed in1991-2000, was followed by a slight expansion during 2004-2005, finally reducing in 2006-2009. The counties with a stroke mortality increase greater than 100% were scattered across the Northeast, Northwest, Central, and South. CONCLUSION: The epidemiological characteristics of both CHD and stroke mortality in China was spatiotemporally featured on the county level during 1991-2009.

Development of a protein-ligand-binding site prediction method based on interaction energy and sequence conservation.

We present a new method for predicting protein-ligand-binding sites based on protein three-dimensional structure and amino acid conservation. This method involves calculation of the van der Waals interaction energy between a protein and many probes placed on the protein surface and subsequent clustering of the probes with low interaction energies to identify the most energetically favorable locus. In addition, it uses amino acid conservation among homologous proteins. Ligand-binding sites were predicted by combining the interaction energy and the amino acid conservation score. The performance of our prediction method was evaluated using a non-redundant dataset of 348 ligand-bound and ligand-unbound protein structure pairs, constructed by filtering entries in a ligand-binding site structure database, LigASite. Ligand-bound structure prediction (bound prediction) indicated that 74.0 % of predicted ligand-binding sites overlapped with real ligand-binding sites by over 25 % of their volume. Ligand-unbound structure prediction (unbound prediction) indicated that 73.9 % of predicted ligand-binding residues overlapped with real ligand-binding residues. The amino acid conservation score improved the average prediction accuracy by 17.0 and 17.6 points for the bound and unbound predictions, respectively. These results demonstrate the effectiveness of the combined use of the interaction energy and amino acid conservation in the ligand-binding site prediction.

Atrial fibrillation increases sympathetic and parasympathetic neurons in the intrinsic cardiac nervous system.

BACKGROUND: Chronic atrial fibrillation (AF) leads to heterogeneous autonomic nerve innervation termed neural remodeling. The quantitative changes in neural density as a function of autonomic remodeling and its association with sustained AF has not been previously determined. METHOD AND RESULTS: Seven dogs (paced group) were chronically paced with electrodes sutured to the epicardium of left atrial appendages. Seven dogs (control animals) were not paced. All paced dogs developed sustained AF by 5 weeks of pacing. The fat pads on the atrial epicardium containing ganglionated plexuses (GP) were separated along with underlying myocardial tissue. Immunocytochemical techniques were used to identify the neurons immunoreactive to anti-tyrosine hydroxylase (TH) and anti-acetylcholine antibodies. After chronic AF, sympathetic and parasympathetic neurons in the atrial intrinsic cardiac ganglia increased significantly. In paced dogs, the density of sympathetic neurons was 3,022 ± 507 µm(2) /mm(2) in the right atrial GP (vs control P < 0.01), 8,571 ± 476 µm(2) /mm(2) in the ventral left atrial GP (vs control P < 0.0001)， 6,422 ± 464 µm(2) /mm(2) in the dorsal atrial GP (vs control P < 0.0001) and 5,392 ± 595 µm(2) /mm(2) in the inferior vena cava-inferior atrial GP (vs control P <0.0001), respectively. The density of parasympathetic neurons was 4,396 ± 877 µm(2) /mm(2) in the right atrial GP, 7,769 ± 465 µm(2) /mm(2) in the ventral left atrial GP， 7,016.47 ± 687 µm(2) /mm(2) in the dorsal atrial GP and 5,485 ± 554 µm(2) /mm(2) in the inferior vena cava-inferior atrial GP, respectively, which was higher than control cohorts in corresponding GP (P < 0.05). CONCLUSIONS: This study provides evidence for the remodeling in atrial intrinsic cardiac ganglia in the dogs with pacing induced AF. A significant increase of sympathetic and parasympathetic neurons was present in atrial intrinsic cardiac ganglia.

The effect of health education video on ocular massage after trabeculectomy.

The aim of this study was to investigate the effect of different ocular massage health education methods on ocular massage in glaucoma patients after trabeculectomy. Eighty-six patients with glaucoma after trabeculectomy (86 eyes) were randomly divided into two health education groups. One group was a watch video group (43 patients, 43 eyes), while the other was an orally taught health education group (43 patients, 43 eyes). Patients were followed up for 1 week, 1 month, and 3, 6, and 12 months after discharge. Records of the patient responses after health education, compliance of patients with follow-up, and intraocular pressure were determined. Measurements included intraocular pressure and differences between the watch video and orally taught health education groups. The differences between the watch video group and orally taught health education group were not statistically significant at 1 week and 1 month, while the differences were statistically significant at 3, 6, and 12 months. The results indicated that health education videos can enable glaucoma patients to have a better mastery of ocular massage after trabeculectomy. According to the needs of patients, health education video use produced good results and should be promoted.

Role of land-ocean interactions in stepwise Northern Hemisphere Glaciation.

The investigation of triggers causing the onset and intensification of Northern Hemisphere Glaciation (NHG) during the late Pliocene is essential for understanding the global climate system, with important implications for projecting future climate changes. Despite their critical roles in the global climate system, influences of land-ocean interactions on high-latitude ice sheets remain largely unexplored. Here, we present a high-resolution Asian dust record from Ocean Drilling Program Site 1208 in the North Pacific, which lies along the main route of the westerlies. Our data indicate that atmosphere-land-ocean interactions affected aeolian dust emissions through modulating moisture and vegetation in dust source regions, highlighting a critical role of terrestrial systems in initiating the NHG as early as 3.6 Myr ago. Combined with additional multi-proxy and model results, we further show that westerly wind strength was enhanced, mainly at low-to-middle tropospheric levels, during major glacial events at about 3.3 and 2.7 Myr ago. We suggest that coupled responses of Earth's surface dynamics and atmospheric circulation in the Plio-Pleistocene likely involved feedbacks related to changes in paleogeography, ocean circulation, and global climate.

Assessment of lisdexamfetamine on executive function in rats: A translational cognitive research.

Executive function, including working memory, attention and inhibitory control, is crucial for decision making, thinking and planning. Lisdexamfetamine, the prodrug of d-amphetamine, has been approved for treating attention-deficit hyperactivity disorder and binge eating disorder, but whether it improves executive function under non-disease condition, as well as the underlying pharmacokinetic and neurochemical properties, remains unclear. Here, using trial unique non-matching to location task and five-choice serial reaction time task of rats, we found lisdexamfetamine (p.o) enhanced spatial working memory and sustained attention under various cognitive load conditions, while d-amphetamine (i.p) only improved these cognitive performances under certain high cognitive load condition. Additionally, lisdexamfetamine evoked less impulsivity than d-amphetamine, indicating lower adverse effect on inhibitory control. In vivo pharmacokinetics showed lisdexamfetamine produced a relative stable and lasting release of amphetamine base both in plasma and in brain tissue, whereas d-amphetamine injection elicited rapid increase and dramatical decrease in amphetamine base levels. Microdialysis revealed lisdexamfetamine caused lasting release of dopamine within the medial prefrontal cortex (mPFC), whereas d-amphetamine produced rapid increase followed by decline to dopamine level. Moreover, lisdexamfetamine elicited more obvious efflux of noradrenaline than that of d-amphetamine. The distinct neurochemical profiles may be partly attributed to the different action of two drugs to membranous catecholamine transporters level within mPFC, detecting by Western Blotting. Taken together, due to its certain pharmacokinetic and catecholamine releasing profiles, lisdexamfetamine produced better pharmacological action to improving executive function. Our finding provided valuable evidence on the ideal pharmacokinetic and neurochemical characteristics of amphetamine-type psychostimulants in cognition enhancement.

Estimation of natural methane emissions from the largest oil sand deposits on earth.

Worldwide methane emission by various industrial sources is one of the important human concerns due to its serious climate and air-quality implications. This study investigates less-considered diffusive natural methane emissions from the world's largest oil sand deposits. An analytical model, considering the first-order methane degradation, in combination with Monte Carlo simulations, is used to quantitatively characterize diffusive methane emissions from Alberta's oil sands formations. The results show that the average diffusive methane emissions from Alberta's oil sands formations is 1.56 × 10-4 kg/m2/year at the 90th percentile of cumulative probability. The results also indicate an annual diffusive methane emissions rate of 0.857 ± 0.013 Million tons of CO2e/year (MtCO2e/year) from Alberta's oil sands formations. This finding suggests that natural diffusive leakages from the oil sands contribute an additional 1.659 ± 0.025 and 5.194 ± 0.079% to recent Canada's 2019 and Alberta's 2020 methane emission estimates from the upstream oil and gas sector, respectively. The developed model combined with Monte Carlo simulations can be used as a tool for assessing methane emissions and current inventories.

Feedback-AVPGAN: Feedback-guided generative adversarial network for generating antiviral peptides.

In this study, we propose Feedback-AVPGAN, a system that aims to computationally generate novel antiviral peptides (AVPs). This system relies on the key premise of the Generative Adversarial Network (GAN) model and the Feedback method. GAN, a generative modeling approach that uses deep learning methods, comprises a generator and a discriminator. The generator is used to generate peptides; the generated proteins are fed to the discriminator to distinguish between the AVPs and non-AVPs. The original GAN design uses actual data to train the discriminator. However, not many AVPs have been experimentally obtained. To solve this problem, we used the Feedback method to allow the discriminator to learn from the existing as well as generated synthetic data. We implemented this method using a classifier module that classifies each peptide sequence generated by the GAN generator as AVP or non-AVP. The classifier uses the transformer network and achieves high classification accuracy. This mechanism enables the efficient generation of peptides with a high probability of exhibiting antiviral activity. Using the Feedback method, we evaluated various algorithms and their performance. Moreover, we modeled the structure of the generated peptides using AlphaFold2 and determined the peptides having similar physicochemical properties and structures to those of known AVPs, although with different sequences.

Study on the mechanisms of action of berberine combined with fluconazole against fluconazole-resistant strains of Talaromyces marneffei.

Talaromyces (Penicillium) marneffei (T. marneffei) is a thermally dimorphic fungus that can cause opportunistic systemic mycoses. Our previous study demonstrated that concomitant use of berberine (BBR) and fluconazole (FLC) showed a synergistic action against FLC-resistant T. marneffei (B4) in vitro. In this paper, we tried to figure out the antifungal mechanisms of BBR and FLC in T. marneffei FLC-resistant. In the microdilution test, the minimum inhibitory concentration (MIC) of FLC was 256 µg/ml before FLC and BBR combination, and was 8 µg/ml after combination, the partial inhibitory concentration index (FICI) of B4 was 0.28. After the treatments of BBR and FLC, the studies revealed that (i) increase reactive oxygen species (ROS), (ii) reduce ergosterol content, (iii) destroy the integrity of cell wall and membrane, (iv) decrease the expression of genes AtrF, MDR1, PMFCZ, and Cyp51B however ABC1 and MFS change are not obvious. These results confirmed that BBR has antifungal effect on T. marneffei, and the combination with FLC can restore the susceptibility of FLC-resistant strains to FLC, and the reduction of ergosterol content and the down-regulation of gene expression of AtrF, Mdr1, PMFCZ, and Cyp51B are the mechanisms of the antifungal effect after the combination, which provides a theoretical basis for the application of BBR in the treatment of Talaromycosis and opens up new ideas for treatment of Talaromycosis.

Identification of prognostic genes and construction of a novel gene signature in the skin melanoma based on the tumor microenvironment.

ABSTRACT: Skin melanoma remains a highly prevalent and yet deadly form of cancer, with the exact degree of melanoma-associated mortality being strongly dependent upon the local tumor microenvironment. The exact composition of stromal and immune cells within this microenvironmental region has the potential to profoundly impact melanoma progression and prognosis. As such, the present study was designed with the goal of clarifying the predictive relevance of stromal and immune cell-related genes in melanoma patients through comprehensive bioinformatics analyses. We therefore analyzed melanoma sample gene expression within The Cancer Genome Atlas database and employed the ESTIMATE algorithm as a means of calculating both stromal and immune scores that were in turn used for identifying differentially expressed genes (DEGs). Subsequently, univariate analyses were used to detect DEGs associated with melanoma patient survival, and through additional functional enrichment analyses, we determined that these survival-related DEGs are largely related to inflammatory and immune responses. A prognostic signature comprised of 10 genes (IL15, CCL8, CLIC2, SAMD9L, TLR2, HLA.DQB1, IGHV1-18, RARRES3, GBP4, APOBEC3G) was generated. This 10-gene signature effectively separated melanoma patients into low- and high-risk groups based upon their survival. These low- and high-risk groups also exhibited distinct immune statuses and differing degrees of immune cell infiltration. In conclusion, our results offer novel insights into a number of microenvironment-associated genes that impact survival outcomes in melanoma patients, potentially highlighting these genes as viable therapeutic targets.

[Mechanism of α-lipoic acid promoting iron efflux in substantia nigra cells of Parkinson's disease rats].

Objective To observe the effect of α-lipoic acid (α-LA) on the expressions of iron regulatory protein 2 (IRP2) and ferroportin1 (FP1) in substantia nigra of rats with Parkinson's disease (PD) and explore the mechanism by which α-LA regulates iron efflux in substantia nigra cells of PD rat models. Methods Sixty healthy male SD rats were randomly divided into a sham group (n=15) and a model group (n=45). To establish the PD model, the rats of the model group were injected with 6-hydroxydopamine (6-OHDA) into their right striatum by the stereotactic technique, and the sham operation group was injected with the same dose of normal saline. Four weeks later, 30 model rats were randomly picked and divided into a PD model group (n=15) and a PD treatment group (n=15). The PD treatment group was intraperitoneally injected with α-LA (50 mg/kg) daily for 2 weeks, and the PD model group was given the same dose of saline. After 14 days of treatment, the left forelimb use rate was tested by cylinder test. The right middle cerebral substantia nigra was taken from each group, and the expression and distribution of tyrosine hydroxylase (TH) was detected by immunohistochemical staining; the number of iron positive cells was determined by Prussian blue staining; and the levels of IRP2 and FP1 were examined by Western blotting. Results Compared with the sham operation group, the left forelimb use rate of the PD model group was significantly reduced. The number of TH positive cells significantly decreased, and the number of iron positive cells in the substantia nigra significantly increased. The level of IRP2 significantly increased, and the level of FP1 decreased remarkably. Compared with PD model group, the left forelimb use rate of the PD treatment group was significantly raised. The number of TH positive cells was significantly elevated, and the number of iron positive cells in the substantia nigra was significantly reduced. The IRP2 level decreased and the FP1 level increased. Conclusion By decreasing the IRP2 level and via the IRP2/IRE pathway, α-LA can increase FP1 level, promote the outflow of iron ions from cells, and reduce iron deposition in the substantia nigra of PD model rats, thereby alleviating brain injury in PD rats induced by 6-OHDA.

In-situ mobilization and transformation of iron oxides-adsorbed arsenate in natural groundwater.

Although reductive dissolution of Fe(III) oxides has been well accepted for As mobilization in alluvial aquifers, the key factors controlling this process are poorly understood. Arsenic(V)-adsorbing ferrihydrite, goethite and hematite were used to examine in-situ mobilization and transformation of adsorbed As(V) and Fe(III) oxides. In the Hetao basin, seven wells with wide ranges of groundwater As were selected to host As(V)-Fe(III) oxides sand. During 80 d experiments, As was firstly desorbed and then released via reductive dissolution of iron oxide from ferrihydrite, while only desorption was observed from goethite/hematite sand. Desorbed As was predominantly controlled by groundwater HCO3- and DOC, while reductive dissolution-related As release was mainly regulated by ORP values, DOC and Fe(II) concentrations. Mineral transformation from ferrihydrite to lepidocrocite and goethite/or mackinawite would also contribute to As release. Arsenic species was transformed from As(V) to As(III) on ferrihydrite, but remained unchanged on goethite and hematite. Arsenic partition between As-Fe(III) oxide sand and real groundwater ranged between 0.012 and 0.102L/g. Kd-sand between As-goethite sand/As-hematite sand and groundwater fell within the ranges observed between sediments and groundwater. This study suggests that As desorption, reductive dissolution and mineral transformation of ferrihydrite would be the major processes controlling As mobility.

Stromal Derived Factor-1/CXCR4 Axis Involved in Bone Marrow Mesenchymal Stem Cells Recruitment to Injured Liver.

The molecular mechanism of bone marrow mesenchymal stromal stem cells (BMSCs) mobilization and migration to the liver was poorly understood. Stromal cell-derived factor-1 (SDF-1) participates in BMSCs homing and migration into injury organs. We try to investigate the role of SDF-1 signaling in BMSCs migration towards injured liver. The expression of CXCR4 in BMSCs at mRNA level and protein level was confirmed by RT-PCR, flow cytometry, and immunocytochemistry. The SDF-1 or liver lysates induced BMSCs migration was detected by transwell inserts. CXCR4 antagonist, AMD3100, and anti-CXCR4 antibody were used to inhibit the migration. The Sprague-Dawley rat liver injury model was established by intraperitoneal injection of thioacetamide. The concentration of SDF-1 increased as modeling time extended, which was determined by ELISA method. The Dir-labeled BMSCs were injected into the liver of the rats through portal vein. The cell migration in the liver was tracked by in vivo imaging system and the fluorescent intensity was measured. In vivo, BMSCs migrated into injured liver which was partially blocked by AMD3100 or anti-CXCR4 antibody. Taken together, the results demonstrated that the migration of BMSCs was regulated by SDF-1/CXCR4 signaling which involved in BMSCs recruitment to injured liver.

Tyrosine Kinase Ligand-Receptor Pair Prediction by Using Support Vector Machine.

Receptor tyrosine kinases are essential proteins involved in cellular differentiation and proliferation in vivo and are heavily involved in allergic diseases, diabetes, and onset/proliferation of cancerous cells. Identifying the interacting partner of this protein, a growth factor ligand, will provide a deeper understanding of cellular proliferation/differentiation and other cell processes. In this study, we developed a method for predicting tyrosine kinase ligand-receptor pairs from their amino acid sequences. We collected tyrosine kinase ligand-receptor pairs from the Database of Interacting Proteins (DIP) and UniProtKB, filtered them by removing sequence redundancy, and used them as a dataset for machine learning and assessment of predictive performance. Our prediction method is based on support vector machines (SVMs), and we evaluated several input features suitable for tyrosine kinase for machine learning and compared and analyzed the results. Using sequence pattern information and domain information extracted from sequences as input features, we obtained 0.996 of the area under the receiver operating characteristic curve. This accuracy is higher than that obtained from general protein-protein interaction pair predictions.

Simultaneous quantification of six main active constituents in Chinese Angelica by high-performance liquid chromatography with photodiode array detector.

BACKGROUND: Angelica sinensis is a famous traditional Chinese medicinalherb, which is predominantly used in the treatment of gynecological conditions. It is the first report for the simultaneous determination of six major active components in Chinese Angelica, which is important for quality control. OBJECTIVE: A validated HPLC-PAD method was first developed to evaluate the quality of crude and processed Radix Angelica through simultaneous determination of six bioactive compounds, namely ferulic acid, senkyunolide I, senkyunolide H, coniferyl ferulate, Z/E-ligustilide and Z/E-butylidenephthalide. MATERIALS AND METHODS: Samples were separated on a Xtimate™C18 column (250 × 4.6 mm, 5 µm) and detected by PAD. Mobile phase was composed of (A) aqueous phosphoric acid (0.02%, v/v) and (B) acetonitrile (MeCN) (including 10% tetrahydrofuran, v/v) using a gradient elution. Analytes were performed at 30°C with a flow rate of 1.0 mL/min. RESULTS: All calibration curves showed good linear regression (r(2) ≥ 0.9963) within the tested ranges, and the recovery of the method was in the range of 91.927-105.859%. CONCLUSION: The results demonstrate that the developed method is accurate and reproducible and could be readily utilized as a suitable quality control method for the quantification of Radix Angelica.

Development of the computerized Mandarin pediatric lexical tone and disyllabic-word picture identification test in noise (MAPPID-N).

MAPPID-N was developed to assess the speech-recognition abilities in noise of Mandarin-speaking children on disyllabic words, and lexical tones in monosyllabic words, in a picture-identification test format. Twenty-six normal-hearing children aged four to nine years listened repeatedly to the test materials where noise was spatially mixed with or separated from speech, in different signal-to-noise (SNR) ratios, to obtain performance-SNR functions and SNR for 50% correct scores (SNR-50%). SNR-50% improved with age only when noise was spatially separated from speech but not when noise was mixed with speech, suggesting the improvement with age in the use of intensity and timing cues differences between the two ears. The homogeneity of the test items was improved by adjusting the intensity levels of individual test items to align their SNR-50% to the mean SNR-50% level.