The evidence regarding vitamin D status and mortality among people with diabetes is scarce. This study aimed to examine the association of serum 25-hydroxyvitamin D 25(OH)D concentrations with ...all-cause and cause-specific mortality among adults with diabetes.
This study included 6,329 adults with diabetes from the Third National Health and Nutrition Examination Survey (NHANES III) and NHANES 2001-2014. Death outcomes were ascertained by linkage to National Death Index records through 31 December 2015. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% CIs for mortality from all causes, cardiovascular disease (CVD), and cancer.
The weighted mean (95% CI) level of serum 25(OH)D was 57.7 (56.6, 58.8) nmol/L, and 46.6% had deficient vitamin D (<50 nmol/L 20 ng/mL). Higher serum 25(OH)D levels were significantly associated with lower levels of glucose, insulin, HOMA of insulin resistance, HbA
, blood lipids, and C-reactive protein at baseline (all
< 0.05). During 55,126 person-years of follow-up, 2,056 deaths were documented, including 605 CVD deaths and 309 cancer deaths. After multivariate adjustment, higher serum 25(OH)D levels were significantly and linearly associated with lower all-cause and CVD mortality: there was a 31% reduced risk of all-cause mortality and a 38% reduced risk of CVD mortality per one-unit increment in natural log-transformed 25(OH)D (both
< 0.001). Compared with participants with 25(OH)D <25 nmol/L, the multivariate-adjusted HRs and 95% CI for participants with 25(OH)D >75 nmol/L were 0.59 (0.43, 0.83) for all-cause mortality (
= 0.003), 0.50 (0.29, 0.86) for CVD mortality (
= 0.02), and 0.49 (0.23, 1.04) for cancer mortality (
= 0.12).
Higher serum 25(OH)D levels were significantly associated with lower all-cause and CVD mortality. These findings suggest that maintaining adequate vitamin D status may lower mortality risk in individuals with diabetes.
Animal studies suggested that exposure to ethylene oxide (EO) might induce hepatic lipid peroxidation and inflammatory lesions in various organs. However, the association between EO exposure and ...diabetes risk in humans is unknown. This study aimed to examine the association of EO exposure with the prevalence of diabetes mellitus in a general population of US adults. This study consisted of 3448 participants aged 20 years and older from the National Health and Nutrition Examination Survey (NHANES) 2013–2014 cycle and 2015–2016 cycle. Circulating levels of EO biomarker (hemoglobin adducts of EO (HbEO)) was measured by using high-performance liquid chromatography coupled with tandem mass spectrometry. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multivariate logistic regression. The weighted median level of HbEO was 29.9 (95% CI: 21.8, 56.0) pmol/g Hb. Elevated levels of HbEO were associated with higher HbA1c and lower high-density lipoprotein cholesterol (both
P
trend
<0.01). After multivariate adjustment including demographics, lifestyle factors, and body mass index (BMI), higher HbEO levels were significantly associated with an increased prevalence of diabetes mellitus. The OR (95% CI) of diabetes across increasing quartiles of HbEO was 1.00 (reference), 1.45 (1.08, 1.96), 1.76 (1.31, 2.36), and 1.77 (1.22, 2.57), respectively (
P
trend
<0.001). Similar results were observed when analyses were stratified by smoking status, age, sex, race/ethnicity, and BMI. In a nationally representative sample of US adults, higher levels of HbEO were significantly associated with an increased prevalence of diabetes mellitus. Further prospective studies are needed to confirm these findings.
Bread wheat is an allohexaploid species with a 16-Gb genome that has large intergenic regions, which presents a big challenge for pinpointing regulatory elements and further revealing the ...transcriptional regulatory mechanisms. Chromatin profiling to characterize the combinatorial patterns of chromatin signatures is a powerful means to detect functional elements and clarify regulatory activities in human studies.
In the present study, through comprehensive analyses of the open chromatin, DNA methylome, seven major chromatin marks, and transcriptomic data generated for seedlings of allohexaploid wheat, we detected distinct chromatin architectural features surrounding various functional elements, including genes, promoters, enhancer-like elements, and transposons. Thousands of new genic regions and cis-regulatory elements are identified based on the combinatorial pattern of chromatin features. Roughly 1.5% of the genome encodes a subset of active regulatory elements, including promoters and enhancer-like elements, which are characterized by a high degree of chromatin openness and histone acetylation, an abundance of CpG islands, and low DNA methylation levels. A comparison across sub-genomes reveals that evolutionary selection on gene regulation is targeted at the sequence and chromatin feature levels. The divergent enrichment of cis-elements between enhancer-like sequences and promoters implies these functional elements are targeted by different transcription factors.
We herein present a systematic epigenomic map for the annotation of cis-regulatory elements in the bread wheat genome, which provides new insights into the connections between chromatin modifications and cis-regulatory activities in allohexaploid wheat.
Main conclusion
Glutamine (Gln) is an efficient nitrogen source in promoting aboveground nitrogen and biomass accumulation in ZD958 (an elite maize hybrid with great potential for further genetic ...improvement) seedlings when conditioning a smaller but adequate root system.
Amino acids account for a significant part of nitrogen (N) resources in the soil. However, how amino acid-N affects crop growth remains to be further investigated. Here, glutamine (Gln) application (80% NH
4
NO
3
+ 20% Gln; mixed N) enhanced shoot growth of the maize hybrid ZD958. N concentration in the shoot increased, which is associated with favorable increases in SPAD values, GS/GOGAT activities, and accumulation of glutamate, asparagine, total free amino acids and soluble proteins in the shoot under mixed N. On the other hand, root growth was reduced when exposed to Gln as indicated by the significantly lower dry weight, root/shoot ratio, and primary, seminal, crown, and total root lengths, as well as unfavorable physiological alterations. Up-regulation of expression of
ZmAMT1.3
,
ZmNRT2.1
, and
ZmAAP2
in the root and that of
ZmAMT1.1
,
ZmAMT1.3
, and
ZmLHT1
in the shoot preconditioned N over-accumulation in the shoot and facilitated shoot growth, presumably via enhancing N translocation to the shoot, when Gln was supplied. Together, Gln is an efficient N source in promoting aboveground N and biomass accumulation in ZD958 seedlings when conditioning a smaller but adequate root system. Notably, ZD958′s parental lines Z58 and Chang7-2 displayed a wide range of variations in Gln responses, which may be partially attributed to single nucleotide polymorphisms (SNPs) in
cis
-elements and coding regions revealed in this study and much larger quantities of unidentified genetic variations between Z58 and Chang7-2. Extensive genetic divergence of these two elite inbred lines implied large potentials for further genetic improvement of ZD958 in relation to organic N use efficiency.
Polyploidization and introgression are major events driving plant genome evolution and influencing crop breeding. However, the mechanisms underlying the higher-order chromatin organization of ...subgenomes and alien chromosomes are largely unknown.
We probe the three-dimensional chromatin architecture of Aikang 58 (AK58), a widely cultivated allohexaploid wheat variety in China carrying the 1RS/1BL translocation chromosome. The regions involved in inter-chromosomal interactions, both within and between subgenomes, have highly similar sequences. Subgenome-specific territories tend to be connected by subgenome-dominant homologous transposable elements (TEs). The alien 1RS chromosomal arm, which was introgressed from rye and differs from its wheat counterpart, has relatively few inter-chromosome interactions with wheat chromosomes. An analysis of local chromatin structures reveals topologically associating domain (TAD)-like regions covering 52% of the AK58 genome, the boundaries of which are enriched with active genes, zinc-finger factor-binding motifs, CHH methylation, and 24-nt small RNAs. The chromatin loops are mostly localized around TAD boundaries, and the number of gene loops is positively associated with gene activity.
The present study reveals the impact of the genetic sequence context on the higher-order chromatin structure and subgenome stability in hexaploid wheat. Specifically, we characterized the sequence homology-mediated inter-chromosome interactions and the non-canonical role of subgenome-biased TEs. Our findings may have profound implications for future investigations of the interplay between genetic sequences and higher-order structures and their consequences on polyploid genome evolution and introgression-based breeding of crop plants.
We investigated the phase separation of dioleoylphosphatidylserine (DOPS) and dipalmitoylphosphatidylcholine (DPPC) in giant unilamellar vesicles in a hypotonic solution using fluorescence and ...confocal laser scanning microscopy. Although phase separation in charged lipid membranes is generally suppressed by the electrostatic repulsion between the charged headgroups, osmotic stress can promote the formation of charged lipid domains. Interestingly, we observed a three-phase coexistence even in the DOPS/DPPC binary lipid mixtures. The three phases were DPPC-rich, dissociated DOPS-rich, and nondissociated DOPS-rich phases. The two forms of DOPS were found to coexist owing to the ionization of the DOPS headgroup, such that the system could be regarded as quasi-ternary. The three formed phases with differently ionized DOPS domains were successfully identified experimentally by monitoring the adsorption of positively charged particles. In addition, coarse-grained molecular dynamics simulations confirmed the stability of the three-phase coexistence. Attraction mediated by hydrogen bonding between protonated DOPS molecules and reduction of the electrostatic interactions at the domain boundaries stabilized the three-phase coexistence.
Metastasis to distant organs is a particularly ominous feature of malignant cancer. LKB1 (also known as STK11) has been identified as a tumor suppressor in several types of cancers. Here, we show ...that LKB1 is at low levels and is negatively associated with poor clinical outcomes in pancreatic cancer (PC). LKB1 is inversely correlated with Snail protein in PC, in which the loss of LKB1 facilitates metastasis through elevating Snail protein level. Furthermore, LKB1 boosts Snail's interaction with E3 ligase FBXL14, leading to increasing ubiquitin‐mediated Snail degradation. Notably, metformin could increase Snail protein ubiquitination via augmenting the location of LKB1 at cytoplasm as well as increasing LKB1 expression. Altogether, our data established that LKB1 impedes invasion and metastasis by decreasing the Snail protein level in PC. Targeting the LKB1/FBXL14/Snail axis may represent a promising therapeutic strategy and metformin might be beneficial for PC therapy through activating the LKB1‐mediated Snail ubiquitination pathway.
LKB1 is negatively correlated with Snail at protein level in pancreatic cancer (PC). Loss of LKB1 promotes PC's metastasis via elevating Snail protein in AMPK‐independent pathway. LKB1 enhances E3 ligase FBXL14 to interact with Snail protein, leading to increasing ubiquitin‐mediated Snail degradation Metformin inhibits metastasis through LKB1‐mediated Snail ubiquitination in PC cells.
Cucumber (
L.) is an important vegetable worldwide, but its yield is affected by a wide range of pathogens and pests. As the major subunit of the exocyst complex, the roles of Exo70 members have been ...shown in
and rice, but their function are unknown in cucumber. Here, we identified 18 CsExo70 members in cucumber, which were divided into three groups (Exo70.1-Exo70.3) and nine subgroups (Exo70A-Exo70I) based on the phylogenetic tree. Subsequently, systematical analyses were performed, including collinearity, gene structure,
-acting elements, conserved motifs, expression patterns, and subcellular localization. Our results showed that
genes were generally expressed in all tissues, and
and
were highly expressed in the stamen. Moreover, the expression levels of most
genes were induced by
pv.
(
) and
f. sp.
Owen (
), especially
and
. In addition, these CsExo70s displayed similar location patterns with discrete and punctate signals in the cytoplasm. Together, our results indicate that CsExo70 members may be involved in plant development and resistance, and provide a reference for future in-depth studies of
genes in cucumber.
Several epidemiological studies have suggested that vitamin D status is associated with risk of dementia in general populations. However, due to the synergistic effect between diabetic pathology and ...neuroinflammation, and the prothrombotic profile in patients with diabetes, whether vitamin D is associated with risk of dementia among patients with diabetes is unclear. This study aimed to investigate the associations of circulating vitamin D levels with risks of all-cause dementia, Alzheimer disease (AD), and vascular dementia (VD) among adults with type 2 diabetes (T2D).
This study included 13,486 individuals (≥60 years) with T2D and free of dementia at recruitment (2006-2010) from the UK Biobank study. Serum 25-hydroxyvitamin D (25OHD) concentrations were measured using the chemiluminescent immunoassay method at recruitment. Serum 25(OH)D ≥ 75 nmol/L was considered sufficient, according to the Endocrine Society Clinical Practice Guidelines. Incidence of all-cause dementia, AD, and VD cases was ascertained using electronic health records (EHRs). Each participant's person-years at risk were calculated from the date of recruitment to the date that dementia was reported, date of death, date of loss to follow-up, or 28 February 2018, whichever occurred first. Among the 13,486 individuals with T2D (mean age, 64.6 years; men, 64.3%), 38.3% had vitamin D ≥ 50 nmol/L and only 9.1% had vitamin D ≥ 75 nmol/L. During a mean follow-up of 8.5 years, we observed 283 cases of all-cause dementia, including 101 AD and 97 VD cases. Restricted cubic spline analysis demonstrated a nonlinear relationship between serum 25(OH)D and risk of all-cause dementia (Pnonlinearity < 0.001) and VD (Pnonlinearity = 0.007), and the nonlinear association reached borderline significance for AD (Pnonlinearity = 0.06), with a threshold at around a serum 25(OH)D value of 50 nmol/L for all the outcomes. Higher serum levels of 25(OH)D were significantly associated with a lower risk of all-cause dementia, AD, and VD. The multivariate hazard ratios and 95% confidence intervals for participants who had serum 25(OH)D ≥ 50 nmol/L, compared with those who were severely deficient (25OHD < 25 nmol/L), were 0.41 (0.29-0.60) for all-cause dementia (Ptrend < 0.001), 0.50 (0.27-0.92) for AD (Ptrend = 0.06), and 0.41 (0.22-0.77) for VD (Ptrend = 0.01). The main limitation of the current analysis was the potential underreporting of dementia cases, as the cases were identified via EHRs.
In this study, we observed that higher concentrations of serum 25(OH)D were significantly associated with a lower risk of all-cause dementia, AD, and VD among individuals with T2D. Our findings, if confirmed by replication, may have relevance for dementia prevention strategies that target improving or maintaining serum vitamin D concentrations among patients with T2D.
Abstract
Piezoelectric devices based on a variety of vibration modes are widely utilized in high-tech fields to make a conversion between mechanical and electrical energies. The excitation of single ...or coupled vibration modes of piezoelectric devices is mainly related to the structure and property of piezoelectric materials. However, for the generally used piezoelectric materials, e.g., lead zirconate titanate ceramics, most of piezoelectric coefficients in the piezoelectric matrix are equal to zero, resulting in many piezoelectric vibration modes cannot be excited, which hinders the design of piezoelectric devices. In this work, an orderly stacked structure with piezoelectric strain units is proposed to achieve all nonzero piezoelectric coefficients, and consequently generate artificially coupled multi-vibration modes with ultrahigh strains. As an example, an orderly stacked structure with two piezoelectric strain units stator, corresponding to 31–36 coupled vibration mode, was designed and fabricated. Based on this orderly stacked structure with two piezoelectric strain units stator, we made a miniature ultrasonic motor (5 mm
Length
× 1.3 mm
Height
× 1.06 mm
Width
). Due to the ultrahigh strain of the 31–36 coupled vibration mode, the velocity per volume of the motor reached 4.66 s
−1
mm
−2
. Furthermore, its moving resolution is around 3 nm, which is two orders higher than that of other piezoelectric motors. This work sheds a light on optimizing the performance of state-of-the-art electromechanical devices and may inspire new devices based on multi-vibration modes.
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