Phosphodiesterases (PDEs) are a superfamily of enzymes that degrade the intracellular second messengers cyclic AMP and cyclic GMP. As essential regulators of cyclic nucleotide signalling with diverse ...physiological functions, PDEs are drug targets for the treatment of various diseases, including heart failure, depression, asthma, inflammation and erectile dysfunction. Of the 12 PDE gene families, cGMP-specific PDE5 carries out the principal cGMP-hydrolysing activity in human corpus cavernosum tissue. It is well known as the target of sildenafil citrate (Viagra) and other similar drugs for the treatment of erectile dysfunction. Despite the pressing need to develop selective PDE inhibitors as therapeutic drugs, only the cAMP-specific PDE4 structures are currently available. Here we present the three-dimensional structures of the catalytic domain (residues 537-860) of human PDE5 complexed with the three drug molecules sildenafil, tadalafil (Cialis) and vardenafil (Levitra). These structures will provide opportunities to design potent and selective PDE inhibitors with improved pharmacological profiles.
Liver can be directly involved in the synthesis and decomposition of fatty acids. Liver lipid deposition is one of the most common chronic liver diseases. Estrogen deficiency can cause lipid ...deposition and energy metabolism disorders in the liver. Sheep bone collagen peptide (SBCP) has been shown to have estrogen-like effects in previous studies. And SBCP has high bioavailability, safety and non-toxic side effects. This study aimed to investigate the effect of SBCP on liver lipid deposition (LLD) caused by estrogen deficiency. Female Wistar rats were treated as follows (n=10): sham group: underwent peri-ovary fat removal operations, ovariectomized rats (model group), ovariectomized rats receiving SBCP treatments: SBCP high dose group (SBCP-H), SBCP medium dose group (SBCP-M) and SBCP low dose group (SBCP-L). After 8 wk, the model group demonstrated severe LLD and liver pathological changes, with increased malondialdehyde (MDA) and free fatty acid (FFA) levels (p<0.05). Additionally, the total superoxide dismutase (T-SOD) activity (p<0.05), serum albumin-to-globulin (A/G) ratio (p<0.05), amount of butyric acid-producing bacteria and short-chain fatty acids (SCFAs) content decreased. SBCP intervention could inhibit the occurrence of LLD and alleviate the liver histopathological damage induced by estrogen deficiency by relieving oxidative stress, preventing the loss of butyric acid-producing bacteria, and decreasing the abundance of Lactobacillus reuteri in the gut. The results suggested that SBCP could improve the LLD indecued by estrogen deficiency.
Globally, grassland degradation is an acute ecological problem. In alpine grassland on the Tibetan Plateau, increased densities of various small mammals in degraded grassland are assumed to intensify ...the degradation process and these mammals are subject to lethal control. However, whether the negative impact of small mammals is solely a result of population size or also a result of activity and behavior has not been tested. In this study, we use plateau pika as a model to compare population size, core area of colony, and the number of burrow entrances and latrines between lightly and severely degraded grassland. We test whether the alleged contribution of pika to grassland degradation is a result of increased population size or increased burrowing activities of individuals in response to lower food abundance. We found that grassland degradation resulted in lower plant species richness, plant height, and biomass. Furthermore, the overall population size of pika was not significantly affected by location in lightly and severely degraded grassland. However, pika core areas in severely grassland degradation were significantly larger and had significantly higher densities of burrows and latrines. Our study provides convincing evidence that habitat‐induced changes in the behavior of small, burrowing mammals, such as pika, can exacerbate grassland degradation. This finding has significant implications for managing small mammals and restoring degraded grassland ecosystems.
Our study demonstrates the changes of behaviour, increased burrowing and enlarged colony territories, of pikas in response to grassland degradation. Our results indicate that the negative impact of plateau pikas on grasslands is through such changes of burrowing and ranging behaviors instead of “population explosion” due to their preference of degraded grassland, as suggested by previous studies.
Climate warming is likely inducing carbon loss from soils of northern ecosystems, but little evidence comes from large-scale observations. Here we used data from a repeated soil survey and remote ...sensing vegetation index to explore changes in soil organic carbon (SOC) stock on the Tibetan Plateau during the past two decades. Our results showed that SOC stock in the top 30 cm depth in alpine grasslands on the plateau amounted to 4.4 Pg C (1 Pg=10¹⁵ g), with an overall average of 3.9 kg C m⁻². SOC changes during 1980s-2004 were estimated at -0.6 g C m⁻² yr⁻¹, ranging from -36.5 to 35.8 g C m⁻² yr⁻¹ at 95% confidence, indicating that SOC stock in the Tibetan alpine grasslands remained relatively stable over the sampling periods. Our findings are nonconsistent with previous reports of loss of soil C in grassland ecosystems due to the accelerated decomposition with warming. In the case of the alpine grasslands on the Tibetan Plateau studied here, we speculate that increased rates of decomposition as soils warmed during the last two decades may have been compensated by increased soil C inputs due to increased grass productivity. These results suggest that soil C stock in terrestrial ecosystems may respond differently to climate change depending on ecosystem type, regional climate pattern, and intensity of human disturbance.
The freshwater snail Lymnaea stagnalis (L. stagnalis) has served as a successful model for studies in the field of Neuroscience. However, a serious drawback in the molecular analysis of the nervous ...system of L. stagnalis has been the lack of large-scale genomic or neuronal transcriptome information, thereby limiting the use of this unique model.
In this study, we report 7,712 distinct EST sequences (median length: 847 nucleotides) of a normalized L. stagnalis central nervous system (CNS) cDNA library, resulting in the largest collection of L. stagnalis neuronal transcriptome data currently available. Approximately 42% of the cDNAs can be translated into more than 100 consecutive amino acids, indicating the high quality of the library. The annotated sequences contribute 12% of the predicted transcriptome size of 20,000. Surprisingly, approximately 37% of the L. stagnalis sequences only have a tBLASTx hit in the EST library of another snail species Aplysia californica (A. californica) even using a low stringency e-value cutoff at 0.01. Using the same cutoff, approximately 67% of the cDNAs have a BLAST hit in the NCBI non-redundant protein and nucleotide sequence databases (nr and nt), suggesting that one third of the sequences may be unique to L. stagnalis. Finally, using the same cutoff (0.01), more than half of the cDNA sequences (54%) do not have a hit in nematode, fruitfly or human genome data, suggesting that the L. stagnalis transcriptome is significantly different from these species as well. The cDNA sequences are enriched in the following gene ontology functional categories: protein binding, hydrolase, transferase, and catalytic enzymes.
This study provides novel molecular insights into the transcriptome of an important molluscan model organism. Our findings will contribute to functional analyses in neurobiology, and comparative evolutionary biology. The L. stagnalis CNS EST database is available at http://www.Lymnaea.org/.
Increased red blood cell distribution width (RDW), which is a marker of anisocytosis, is associated with mortality and cardiovascular events in the general population and in patients with heart ...failure or coronary heart disease. We investigated whether RDW in acute cerebral infarction is predictive of functional outcome and mortality. A total of 847 consecutive patients with first-ever acute cerebral infarction who presented to the emergency department within seven days of symptom onset were enrolled in this study. We investigated the association of RDW with poor functional outcome (modified Rankin Scale >2) and all-cause mortality at three months, as well as survival time for one year after stroke onset. Multivariate logistic regression revealed that higher RDW was independently associated with poor functional outcome (adjusted odds ratio OR, 1.222 per 1% increment in RDW, 95% confidence interval CI 1.059–1.409, p=0.006) and all-cause death (adjusted OR, 1.395 per 1% increment in RDW, 95% CI 1.168–1.665, p<0.001) at three months after stroke onset. RDW was an independent predictor of survival in multivariate Cox-proportional regression model (adjusted hazard ratio, 1.328 per 1% increment in RDW, 95%CI 1.178–1.498, p<0.001). The addition of RDW to a survival model significantly increased predictability for survival across the entire follow-up period (weighted average of the area-under the curves, 0.858 vs. 0.841, p<0.05). In conclusion, higher RDW measured in cases of acute stage cerebral infarction was associated with poor functional outcome and mortality. RDW may be used as a biomarker for the prediction of long-term outcomes in patients with acute cerebral infarction.
Abstract
The origin of complex organic molecules (COMs) in young Class 0 protostars has been one of the major questions in astrochemistry and star formation. While COMs are thought to form on icy ...dust grains via gas-grain chemistry, observational constraints on their formation pathways have been limited to gas-phase detection. Sensitive mid-infrared spectroscopy with JWST enables unprecedented investigation of COM formation by measuring their ice absorption features. Mid-infrared emission from disks and outflows provide complementary constraints on the protostellar systems. We present an overview of JWST/Mid-Infrared Instrument (MIRI) Medium Resolution Spectroscopy (MRS) and imaging of a young Class 0 protostar, IRAS 15398−3359, and identify several major solid-state absorption features in the 4.9–28
μ
m wavelength range. These can be attributed to common ice species, such as H
2
O, CH
3
OH, NH
3
, and CH
4
, and may have contributions from more complex organic species, such as C
2
H
5
OH and CH
3
CHO. In addition to ice features, the MRS spectra show many weaker emission lines at 6–8
μ
m, which are due to warm CO gas and water vapor, possibly from a young embedded disk previously unseen. Finally, we detect emission lines from Fe
ii
, Ne
ii
, S
i
, and H
2
, tracing a bipolar jet and outflow cavities. MIRI imaging serendipitously covers the southwestern (blueshifted) outflow lobe of IRAS 15398−3359, showing four shell-like structures similar to the outflows traced by molecular emission at submillimeter wavelengths. This overview analysis highlights the vast potential of JWST/MIRI observations and previews scientific discoveries in the coming years.
Similar to worldwide trends, the incidence of thyroid cancer in South Korea has increased steadily in recent decades. We examined the trends in thyroid cancer incidence in Gwangju and Jeonnam ...provinces between 1996 and 2010, and identified 19 881 cases (men 3282/16.5%; women 16 599/83.5%) from the Gwangju Cancer Registry and Jeonnam Cancer Registry databases, which are population-based cancer registries. Age-standardized incidence rates per 100 000 persons, using hypothetical world standard population (Segi), increased from 1.9 in 1996 to 27.0 in 2010 in men, and from 10.6 to 111.3 in women, respectively. The estimated annual percentage changes (95% confidence interval) of age-standardized incidence rates were 27.1% (24.6-29.6) and 19.7% (16.4-23.2) for men and women, respectively, during the same period. The proportion of papillary-type thyroid cancer increased from 74.2 and 75.4% in 1996 to 97.9 and 98.3% in 2010 for men and women, respectively. We found the most prominent increasing trends and the highest incidence rate of thyroid cancer among those that have ever been reported. Thyroid cancer has been the leading cancer in women since 2003 and is now the fifth most common cancer in men in Gwangju and Jeonnam, South Korea.
Sudden infant death syndrome (SIDS) still remains one of the leading causes of infant death worldwide, especially in high-income countries. To date, however, there is no detailed information on the ...global health burden of SIDS.
To characterize the global disease burden of SIDS and its trends from 1990 to 2019 and to compare the burden of SIDS according to the socio-demographic index (SDI).
Systematic analysis based on the Global Burden of Disease (GBD) 2019 data.
Epidemiological data of 204 countries from 1990 to 2019 were collected via various methods including civil registration and vital statistics in the original GBD study. Estimates for mortality and disease burden of SIDS were modelled. Crude mortality and mortality rates per 100,000 population were analyzed. Disability-adjusted life years (DALYs) and DALY rates were also assessed.
In 2019, mortality rate of SIDS accounted for 20.98 95% Uncertainty Interval (UI), 9.15 to 46.16 globally, which was a 51% decrease from 1990. SIDS was most prevalent in Western sub-Saharan Africa, High-income North America and Oceania in 2019. The burden of SIDS was higher in males than females consistently from 1990 to 2019. Higher SDI and income level was associated with lower burden of SIDS; further, countries with higher SDI and income had greater decreases in SIDS burden from 1990 to 2019.
The burden of SIDS has decreased drastically from 1990 to 2019. However, the improvements have occurred disproportionately between regions and SDI levels. Focused preventive efforts in under-resourced populations are needed.
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