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Growing evidence has indicated the association of clinical antibiotic use with abnormal blood lipid levels; however, no epidemiological study has examined the relationship of antibiotic exposure, probably derived from food chains, with blood lipid levels. This study investigated the relationships of urinary antibiotic levels with blood lipid levels and dyslipidemias in the older population. Baseline data of 960 participants from the Cohort of Elderly Health and Environment Controllable Factors were used in the present study. High-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was performed to detect antibiotic residues in the urine samples of the participants. Our findings revealed that each 1 μg/g increase in enrofloxacin and ciprofloxacin levels was associated with an increase of 0.084 (95 % confidence interval (CI): 0.030, 0.139) and 0.049 (95 % CI : 0.012, 0.086) in triglyceride levels, respectively. Enrofloxacin was associated with an increased risk of hypertriglyceridemia. Each 1 μg/g increase in the enrofloxacin level corresponded to an increase of 0.052 (95 % CI : 0.006, 0.098) in the low-density lipoprotein cholesterol level. Furthermore, florfenicol exposure increased the risks of both hyperbetalipoproteinemia and hypoalphalipoproteinemia. By contrast, each 1 μg/g increase in sulfaclozine and doxycycline levels was associated with a − 0.062 (95 % CI : −0.111, −0.020), and − 0.083 (95 % CI : −0.160, −0.007) decrease in total cholesterol levels, respectively. Sulfaclozine was closely related to a decreased risk of hypercholesterolemia. Stratification analysis revealed specific differences in the correlation between antibiotic exposure and lipid levels based on the waist circumference (WC) values of the participants. Except for sulfaclozine and doxycycline, other antibiotics exerted adverse effects on lipid levels and increased dyslipidemia prevalence. The older participants with higher WC values were vulnerable to antibiotic exposure. Therefore, an appropriate understanding of the epidemiological attributes of antibiotic residues is indispensable to prevent abdominal obesity in the older population. [Display omitted] • Doxycycline exposure was negatively correlated with TG levels. • Doxycycline exposure was linked to a reduced risk of hypertriglyceridemia. • Macrolide exposure was related to hypercholesterolemia and hypertriglyceridemia. • WC discrepancy intervened the associations between antibiotics and blood lipids. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is the most common neurodegenerative disorder in the world. The aggregation of both amyloid beta (Aβ) peptides extracellularly and Tau proteins intracellularly plays key roles in the pathological consequences of AD, which lead to cholinergic neurodegeneration and eventually death. Currently, there are no effective methods to stop the progression of AD. Using ex vivo , in vivo and clinical approaches, we investigated the functional effects of plasminogen on the widely used FAD, Aβ42 oligomer or Tau intracranial injection-induced AD mouse model and explored its therapeutic effects on patients with AD. The results show that intravenously injected plasminogen rapidly crosses the blood‒brain barrier (BBB); increases plasmin activity in the brain; colocalizes with and effectively promotes the clearance of Aβ42 peptide and Tau protein deposits ex vivo and in vivo ; increases the choline acetyltransferase (ChAT) level and decreases the acetylcholinesterase (AChE) activity; and improves the memory functions. Clinically, when GMP-level plasminogen was administered to 6 AD patients for 1–2 weeks, their average scores on the Minimum Mental State Examination (MMSE), which is a standard scoring system used to measure the memory loss and cognitive deficits, were extremely significantly improved by 4.2 ± 2.23 points, e.g., an average increase from 15.5 ± 8.22 before treatment to 19.7 ± 7.09 after treatment. The preclinical study and pilot clinical study suggest that plasminogen is effective in treating AD and may be a promising drug candidate. • Plasminogen crosses the blood‒brain barrier (BBB) and increases plasmin activity in the brain. • Plasminogen promotes the clearance of Aβ42 peptide and Tau protein. • Plasminogen improves the memory functions in AD mouse model. • Plasminogen increases the Minimum Mental State Examination (MMSE) score in AD patients. [ABSTRACT FROM AUTHOR]

Fiber quality is a major breeding goal in cotton, but phenotypically direct selection is often hindered. In this study, we identified fiber quality and yield related loci using GWAS based on 2.97 million SNPs obtained from 10.65× resequencing data of 1081 accessions. The results showed that 585 novel fiber loci, including two novel stable SNP peaks associated with fiber length on chromosomes At12 and Dt05 and one novel genome regions linked with fiber strength on chromosome Dt12 were identified. Furthermore, by means of gene expression analysis, GhM_A12G0090 , GhM_D05G1692 , GhM_D12G3135 were identified and GhM_D11G2208 function was identified in Arabidopsis. Additionally, 14 consistent and stable superior haplotypes were identified, and 25 accessions were detected as possessing these 14 superior haplotype in breeding. This study providing fundamental insight relevant to identification of genes associated with fiber quality and yield will enhance future efforts toward improvement of upland cotton. • A total of 909 novel fiber and yield loci were detected via WGRS with 10.65× coverage depth in 1,081 cotton accessions. • Three novel stable SNP peaks associated with FL and FS were found. • GhM_D11G2208 can promote cell elongation based up leaf trichome and dark-grown hypocotyls in Arabidopsis. • 14 consistent and stable superior haplotypes were detected based on 915 SNPs in Dt11 region. [ABSTRACT FROM AUTHOR]

The evidence of interactive effect of the toxic metal (TM) mixture and apolipoprotein E (APOE) ε4 gene on cognitive impairment in older adults is scarce. We aimed to explore whether the associations of single TMs and their mixture with cognitive impairment depend on APOE ε4 in Chinese community-dwelling older people. A total of 1148 older adults from a subset of the baseline survey of a cohort study were included. Blood arsenic (As), cadmium (Cd), lead (Pb), strontium (Sr), and vanadium (V) were detected by inductively coupled plasma mass spectrometry. APOE gene (rs429358, rs7412) polymorphisms were analyzed by the Polymerase Chain Reaction instrument. Mixed effects logistic regression was applied to estimate the relationships of single TMs and APOE genotype with cognitive impairment. Weighted quantile sum (WQS) and Bayesian kernel machine regression (BKMR) models were performed to examine joint impacts of the TM mixture, as well as the interaction of the TM mixture with APOE ε4 genotype on cognitive impairment. Pb displayed a significant linear association with an increased odds of cognitive impairment after adjustment for covariates (P trend = 0.045). While APOE genotype did not show a significant correlation with cognitive impairment. WQS showed that the TM mixture was associated with an increased risk of cognitive impairment by 31.0% (OR= 1.31, 95% CI: 0.92, 1.87) while no significance was found. BKMR exhibited a significant linear association between the TM mixture and cognitive impairment. Moreover, both WQS and BKMR indicated that Pb contributed the most to cognitive impairment within the mixture. Significant interactions of Pb or the TM mixture and APOE genotype on cognitive impairment were observed, contributing to 38.1% and 38.2% of total effects, respectively. APOE ε4 allele amplifies the associations of single Pb or the TM mixture with cognitive impairment. These findings may help to develop precision prevention. [Display omitted] • The TM mixture showed a positive association with cognitive impairment, in which Pb was the most contributor in the mixture. • APOE ε4 genotype amplified the associations of Pb and the TM mixture with cognitive impairment in older adults. • Attributable proportions due to interaction effects of Pb and the mixture with APOE ε4 were 38.1% and 38.2%, respectively. [ABSTRACT FROM AUTHOR]

Three novel Mn(II)/Co(II)-based 3D metal-organic frameworks (MOFs), namely {[Mn 2 (L)(tib)(H 2 O)]·3DMA·4H 2 O} n (1), {[Co 2 (L)(bipd) 2 ]·3H 2 O} n (2) and {[Co(L) 0.5 (bimb)]·3H 2 O·0.5O 2 } n (3) (H 4 L ​= ​5,5'-(1,4-xylylenediamino) diisophthalic acid, tib ​= ​1,3,5-tris(1-imidazolyl)benzene, bipd ​= ​3,5-bis(1-imidazoly)pyridine, and bimb ​= ​1,4-bis(lmidazol)-butane), have been successfully synthesized using the mixed-ligand as functionalized organic linker. The structural characterization revealed that both MOFs 1 and 2 exhibited an unprecedented 4-nodal 3D framework that enriching crystal engineering, while MOF 3 featured a 2-nodal three-interpenetrating bbf topology framework with a Schläfli symbol of (64·82)(66) 2. The title MOFs have been exploited as photocatalysts for degradation of methylene blue (MB), methyl violet (MV) and malachite green (MG). The photocatalytic results demonstrated that MOFs 2 and 3 exhibited efficient photocatalytic abilities to degrade the three aromatic dyes under UV irradiation. The possible catalytic mechanism was also explored and discussed in detail. Moreover, the variable-temperature magnetic analyses indicated that MOFs 1 – 3 exhibited weak antiferromagnetic behavior between Mn(II)/Co(II) ions. [Display omitted] • Three novel Mn(II)/Co(II)-based 3D MOFs under solvothermal or hydrothermal condition in one-step, for the first time, were synthesized. • The MOFs 2 and 3 act as efficient heterogeneous photocatalyst for degradation of three aromatic dyes. • The possible catalytic mechanism was explored and discussed in detail. • MOFs 1 – 3 exhibit antiferromagnetic coupling between neighboring central ions. [ABSTRACT FROM AUTHOR]

Neuroinflammation is critically involved in nerve injury-induced neuropathic pain, characterized by local and systemic increased levels of proinflammatory cytokines. Interleukin-24 (IL-24), a key member of the IL-10 family, has been extensively studied for its therapeutic potential in various diseases, including cancer, autoimmune disorders, and bacterial infections, but whether it is involved in the regulation of neuropathic pain caused by peripheral nerve injury (PNI) has not been well established. In this study, we reported that spared nerve injury (SNI) induced a significant upregulation of IL-24 in fibroblasts, neurons, and oligodendrocyte precursor cells (OPCs, also called NG2-glia) in the affected spinal dorsal horns (SDHs), as well as dorsal root ganglions (DRGs). We also found that tumor necrosis factor α (TNF-α) induced the transcriptional expression of IL-24 in cultured fibroblasts, neurons, and NG2-glia; in addition, astrocytes, microglia, and NG2-glia treated with TNF-α exhibited a prominent increase in interleukin-20 receptor 2 (IL-20R2) expression. Furthermore, we evaluated the ability of IL-24 and IL-20R2 to attenuate pain in preclinical models of neuropathic pain. Intrathecal (i.t.) injection of IL-24 neutralizing antibody or IL-20R2 neutralizing antibody could effectively alleviate mechanical allodynia and thermal hyperalgesia after PNI. Similarly, intrathecal injection of IL-24 siRNA or IL-20R2 siRNA also alleviated mechanical allodynia after SNI. The inhibition of IL-24 reduced SNI-induced proinflammatory cytokine (IL-1β and TNF-α) production and increased anti-inflammatory cytokine (IL-10) production. Meanwhile, the inhibition of IL-20R2 also decreased IL-1β mRNA expression after SNI. Collectively, our findings revealed that IL-24/IL-20R might contribute to neuropathic pain through inflammatory response. Therefore, targeting IL-24 could be a promising strategy for treating neuropathic pain induced by PNI. [Display omitted] • IL-24 was secreted by activated fibroblasts, neurons and NG2-glia after SNI. • TNF-α induced IL-20R2 expression in cultured astrocytes, microglia and NG2-glia. • Inhibiting IL-24 or IL-20R2 significantly ameliorated PNI-induced neuropathic pain. [ABSTRACT FROM AUTHOR]

In this paper, we study the parkinson oscillation mechanism in a computational model by bifurcation analysis and numerical simulation. Oscillatory activities can be induced by abnormal coupling weights and delays. The bidirectional Hopf bifurcation phenomena are found in simulations, which can uniformly explain the oscillation mechanism in this model. The Hopf1 represents the transition between the low firing rate stable state (SS) and oscillation state (OS), the Hopf2 represents the transition between the high firing rate stable state (HSS) and the OS, the mechanisms of them are different. The Hopf1 and Hopf2 bifurcations both show that when the state transfers from the stable region to the oscillation region, oscillatory activities originate from the beta frequency band or the gamma frequency band. We find that the changing trends of the frequency (DF) and oscillation amplitude (OSAM) are contrary in many cases. The effect of the delay in inhibitory pathways is greater than that of in excitatory pathways, and appropriate delays improve the discharge activation level (DAL) of the system. In all, we infer that oscillations can be induced by the follow factors: 1. Improvement of the DAL of the globus pallidus externa (GPe); 2. Reduce the DAL of the GPe from the HSS or the discharge saturation state; 3. The GPe can also resonate with the subthalamic nucleus (STN). [ABSTRACT FROM AUTHOR]

Two novel Co (II) MOFs based on 5-(4-(imidazolyl-1-yl)phenyl) isophthalic acid (H 2 L), namely [Co(L)(tib)(H 2 O) 2 ] n (CP 1) and [Co(L)(bip) 0.5 ] n (CP 2) (tib ​= ​1,3,5-tirs (1-imidazolyl) benzene, bip ​= ​3,5-bis(1-imidazolyl) pyridine ether) have been synthesized under solvothermal conditions and characterized by powder X-ray diffraction, single crystal X-ray diffraction. The photodegradation studies demonstrate that CPs 1 – 2 show high-efficiency degradation of MV (Methyl violet), and the mechanism studies demonstrate that the main active species are ⋅OH radicals. Meanwhile, electrochemistry studies demonstrate that CPs 1 – 2 can catalyze water oxidation under alkaline conditions, and CPs 1 – 2 only need the overpotential of 348 ​mV–760 mV to deliver the current density of 1 ​mA ​cm−2. Two novel Co (II) MOFs (CP 1 and CP 2) have been synthesized by H 2 L, tib, and bip. The photodegradation studies demonstrate that CPs 1-2 show high-efficiency degradation of MV. Simultaneously, electrochemistry studies show that CPs 1-2 could catalyze water oxidation with relatively low overpotential. [Display omitted] • Two novel Co-based MOFs were synthesized by solvothermal method. • Exhibit efficient photocatalytic degradation abilities towards MV/MB in aqueous solution. • Only need the overpotential of 348 ​mV–760 mV to deliver the current density of 1 ​mA ​cm−2. [ABSTRACT FROM AUTHOR]

Angiogenesis is critical for many diseases. Previously, we reported that Down Syndrome Candidate Region 1 isoform 1L (DSCR1-1L) was one of the most up-regulated genes in endothelial cells induced by VEGF and histamine, and regulated endothelial cell proliferation and Matrigel angiogenesis in mice. However, it was not known whether DSCR1-1L regulated angiogenesis in vivo and what was the molecular mechanism underlying it. In this study, gene knockdown and overexpression models were established to study the role of DSCR1-1L in angiogenesis in vivo. Further, the downstream regulatory target of DSCR1-1L was explored with molecular biological methods in vascular endothelial cells. We found that DSCR1-1L shRNAs significantly inhibited angiogenesis induced by VEGF in mice (p < 0.0001). In the gain-of-function assay, overexpression of DSCR1-1L cDNA in mouse endothelium of EC-FH-DSCR1-1L transgenic mice was sufficient to induce angiogenesis significantly (p < 0.01). DSCR1-1L regulated angiogenesis in the early stage by down-regulation of the VE-cadherin expression through targeting its transcription, but not mRNA stability. Three DSCR1-1L-targeted DNA elements in the VE-cadherin promoter were identified by promoter reporter assays, among which, a novel specific transcriptional complex was found. The DNA sequence (CTTCTG) in the VE-cadherin promoter was identified to directly interact with proteins by Electrophoresis Mobility Shift Assays and DNase I footprint assay. Hence, DSCR1-1L is an excellent therapeutic target for angiogenic diseases through down-regulating the formation of a novel transcriptional complex on the VE-cadherin promoter. DSCR1-1L shRNAs and cDNA have the potential to be developed for clinical application. Our results also contribute significantly to the field of mechanistic studies. • Down Syndrome Candidate Region 1 Isoform 1L shRNAs inhibited angiogenesis in vivo. • overexpression of DSCR1-1L cDNA in mouse endothelium was induce angiogenesis. • DSCR1-1L down-regulated the VE-cadherin transcription, but not mRNA stability. • A novel specific transcriptional complex regulated by DSCR1-1L was found. • The DNA sequence was identified to directly interact with proteins. [ABSTRACT FROM AUTHOR]