Artificial sweeteners and risk of incident cardiovascular disease and mortality: evidence from UK Biobank.

BACKGROUND: Artificial sweeteners are widely popular worldwide as substitutes for sugar or caloric sweeteners, but there are still several important unknowns and controversies regarding their associations with cardiovascular disease (CVD). We aimed to extensively assess the association and subgroup variability between artificial sweeteners and CVD and CVD mortality in the UK Biobank cohort, and further investigate the modification effects of genetic susceptibility and the mediation role of type 2 diabetes mellitus (T2DM). METHODS: This study included 133,285 participants in the UK Biobank who were free of CVD and diabetes at recruitment. Artificial sweetener intake was obtained from repeated 24-hour diet recalls. Cox proportional hazard models were used to estimate HRs. Genetic predisposition was estimated using the polygenic risk score (PRS). Furthermore, time-dependent mediation was performed. RESULTS: In our study, artificial sweetener intake (each teaspoon increase) was significantly associated with an increased risk of incident overall CVD (HR1.012, 95%CI: 1.008,1.017), coronary artery disease (CAD) (HR: 1.018, 95%CI: 1.001,1.035), peripheral arterial disease (PAD) (HR: 1.035, 95%CI: 1.010,1.061), and marginally significantly associated with heart failure (HF) risk (HR: 1.018, 95%CI: 0.999,1.038). In stratified analyses, non-whites were at greater risk of incident overall CVD from artificial sweetener. People with no obesity (BMI < 30 kg/m2) also tended to be at greater risk of incident CVD from artificial sweetener, although the obesity interaction is not significant. Meanwhile, the CVD risk associated with artificial sweeteners is independent of genetic susceptibility, and no significant interaction exists between genetic susceptibility and artificial sweeteners in terms of either additive or multiplicative effects. Furthermore, our study revealed that the relationship between artificial sweetener intake and overall CVD is significantly mediated, in large part, by prior T2DM (proportion of indirect effect: 70.0%). In specific CVD subtypes (CAD, PAD, and HF), the proportion of indirect effects ranges from 68.2 to 79.9%. CONCLUSIONS: Our findings suggest significant or marginally significant associations between artificial sweeteners and CVD and its subtypes (CAD, PAD, and HF). The associations are independent of genetic predisposition and are mediated primarily by T2DM. Therefore, the large-scale application of artificial sweeteners should be prudent, and the responses of individuals with different characteristics to artificial sweeteners should be better characterized to guide consumers' artificial sweeteners consumption behavior.

Sustainable inflammatory activation following spinal cord injury is driven by thrombin-mediated dynamic expression of astrocytic chemokines.

Acute spinal cord injury (SCI) always results in sustainable recruitment of inflammatory cells driven by sequentially generated chemokines, thereby eliciting excessive neuroinflammation. However, the underlying mechanism of temporally produced chemokines remains elusive. Reactive astrocytes are known to be the main sources of chemokines at the lesion site, which can be immediately activated by thrombin following SCI. In the present study, SCI was shown to induce a sequential production of chemokines CCL2 and CCL5 from astrocytes, which were associated with a persistent infiltration of macrophages/microglia. The rapidly induced CCL2 and later induced CCL5 from astrocytes were regulated by thrombin at the damaged tissues. Investigation of the regulatory mechanism revealed that thrombin facilitated astrocytic CCL2 production through activation of ERK/JNK/NFκB pathway, whereas promoted CCL5 production through PLCß3/NFκB and ERK/JNK/NFκB signal pathway. Inhibition of thrombin activity significantly decreased production of astrocytic CCL2 and CCL5, and reduced the accumulation of macrophages/microglia at the lesion site. Accordingly, the locomotor function of rats was remarkably improved. The present study has provided a new regulatory mechanism on thrombin-mediated sequential production of astrocytic chemokines, which might be beneficial for clinical therapy of CNS neuroinflammation.

Ill-fitting prosthesis is associated with an increased risk of elevated blood pressures.

OBJECTIVE: Previous studies focused on the benefits of adequate prosthodontic treatment, while few studies have investigated the prosthodontic-related risks to health. As a modifiable oral health indicator, the association of ill-fitting prosthesis (IFP) with hypertension has not been fully explored. METHODS: This cross-sectional study involved 158,659 adults in Beijing (2009-2017) receiving intra-oral examinations and blood pressure measurements. Logistic regression models were applied to assess the association of IFP with the prevalence of hypertension, systolic blood pressure (SBP) ≧ 140 mmHg and diastolic blood pressure (DBP) ≧ 90 mmHg, as well as subgroup analyses by different fixed IFP subgroups (according to involved teeth number) and removable IFP subgroup. We further investigated effect modifications among stratified populations. RESULTS: 158,659 individuals were included for analysis, 346 (26.86%) in IFP group and 27,380 (17.40%) in non-IFP group (p < 0.001) were hypertensive. After adjustment of sex, age, obesity, dyslipidaemia, diabetes, hsCRP, family history of CVD, self-reported smoking, self-reported drinking and WC, ORs of hypertension, SBP ≧ 140 mmHg and DBP ≧ 90 mmHg were 1.330 (95% CI: 1.162-1.522), 1.277 (95% CI: 1.098-1.486) and 1.376 (95% CI: 1.186-1.596), respectively (p < 0.05). Furthermore, after full adjustment, the number of involved teeth showed a significant incremental trend with hypertension risk in the population with and without IFP (p for trend <0.001). The IFP-blood pressure associations were more pronounced in females, 18-60 years, non-obese and diabetic participants. CONCLUSION: As a modifiable oral indicator, IFP was significantly associated with a higher risk of hypertension.

Gcc1 homologs regulate growth, oxidative stress, conidiation and appressorium formation in Colletotrichum siamense and Colletotrichum graminicola.

The Zn2Cys6 transcription factor is a fungal-specific zinc finger protein, which plays an important role in regulating growth, development and pathogenicity of pathogenic fungi. In this study, we characterized two Zn2Cys6 transcription factors, CsGcc1 and CgrGcc1 in Colletotrichum siamense and C. graminicola, respectively, which are homologous to Gcc1 in Magnaporthe oryzae. Both CsGcc1 and CgrGcc1 contain a typical GAL4 DNA-binding domain. Deletion of CsGCC1 or CgrGCC1 decreased the growth rate and lowered the tolerance to H2O2. In addition, disrupting CsGCC1 reduced conidial yield and lowered the germination rate and appressorium formation rate of C. siamense. Cellophane assays showed that deletion of CsGCC1 also weakened the penetration ability of appressoria. In C. graminicola, CgrGcc1 did not affect the production and germination of oval conidia, but its deletion significantly decreased the yield of the falcate conidium, and led to abnormal appressorium formation. In terms of pathogenicity, CsGcc1 slightly reduced the virulence of C. siamense, while deleting CgrGcc1 did not affect virulence of C. graminicola. In conclusion, the Zn2Cys6 transcription factors CsGcc1 and CgrGcc1 are involved in the regulation of vegetative growth, oxidative stress, conidial/falcate conidial production and appressorium formation in C. siamense and C. graminicola.

Pogostemon cablin (Blanco) Benth granule revealed a positive effect on improving intestinal barrier function and fecal microbiota in mice with irinotecan-induced intestinal mucositis.

Pogostemon cablin (Blanco) Benth (PCB), a medicinal and edible homologous Chinese herb, has a protective effect on the structure and function of intestine. In this study, we aimed to investigate the effect of PCB granule (PCBG) on the improvement of irinotecan-induced intestinal mucositis and the regulation of intestinal microorganisms in mice. Our results demonstrated that PCBG supplementation significantly improved diarrhea symptoms caused by irinotecan, as evidenced by inhibiting weight loss, reversing intestinal atrophy, protecting against splenomegaly and balancing oxidative stress. Furthermore, compared with the model group, PCBG restored the intestinal morphology and improved intestinal barrier dysfunction by promoting the expression of tight junction proteins and mucin. Moreover, high-throughput sequencing analysis revealed that PCBG improved the flora disorder caused by irinotecan and regulated microbial community structure, such as decreasing the relative abundance of Bacteroides as well as increasing the relative abundance of Lactobacillus. Meanwhile, the disordered microbial functions in intestinal mucositis mice were recovered more closely to the controls by PCBG. Finally, we found that a robust correlation between the specific microbiota and intestinal mucositis-related index. In summary, these findings revealed the beneficial effects of PCBG on the intestinal barrier and gut microbiota of irinotecan-induced intestinal mucositis, which may be one of the potential strategies to reduce the clinical side effects of irinotecan.

Advanced porous organic materials for sample preparation in pharmaceutical analysis.

The development of novel sample preparation media plays a crucial role in pharmaceutical analysis. To facilitate the extraction and enrichment of pharmaceutical molecules in complex samples, various functionalized materials have been developed and prepared as adsorbents. Recently, some functionalized porous organic materials have become adsorbents for pharmaceutical analysis due to their unique properties of adsorption and recognition. These advanced porous organic materials, combined with consequent analytical techniques, have been successfully used for pharmaceutical analysis in complex samples such as environmental and biological samples. This review encapsulates the progress of advanced porous materials for pharmaceutical analysis including pesticides, antibiotics, chiral drugs, and other compounds in the past decade. In addition, we also address the limitations and future trends of these porous organic materials in pharmaceutical analysis.

Macrophage Migration Inhibitory Factor Promotes Expression of Matrix Metalloproteinases 1 and 3 in Spinal Cord Astrocytes following Gecko Tail Amputation.

BACKGROUND: The matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases that play a variety of physiological and pathological roles in development, remodeling of tissues and diseases, mainly through degradation of various components of the extracellular matrix (ECM). Particularly, the MMPs have increasingly been found to mediate neuropathology following spinal cord injury (SCI). Proinflammatory mediators are potent activators of the MMPs. However, how the spinal cord regenerative vertebrates circumvent MMPs-mediated neuropathogenesis following SCI remains unclear. METHODS: Following the establishment of gecko tail amputation model, the correlation of MMP-1 (gMMP-1) and MMP-3 (gMMP-3) expression with that of macrophage migration inhibitory factor in gecko (gMIF) was assayed by RT-PCR, Western blot and immunohistochemistry. Transcriptome sequencing of primary astrocytes was performed to analyze the intracellular signal transduction of macrophage migration inhibitory factor (MIF). The effects of MMP-1 and MMP-3 induced by MIF on astrocyte migration were assessed by transwell migration assay. RESULTS: The expression of gMIF significantly increased at lesion site of the injured cord, in parallel with those of gMMP-1 and gMMP-3 in the gecko astrocytes (gAS). Transcriptome sequencing and in vitro cell model revealed that gMIF efficiently promoted the expression of gMMP-1 and gMMP-3 in gAS, which in turn contributed to the migration of gAS. Inhibition of gMIF activity following gecko SCI remarkably attenuated astrocytic expression of the two MMPs, and further influenced gecko tail regeneration. CONCLUSIONS: Gecko SCI following tail amputation promoted production of gMIF, which induced the expression of gMMP-1 and gMMP-3 in gAS. The gMIF-mediated gMMP-1 and gMMP-3 expression was involved in gAS migration and successful tail regeneration.

Association of the components of ambient fine particulate matter (PM2.5) and chronic kidney disease prevalence in China.

Previous research has implicated PM2.5 as a potential environmental risk factor for CKD, but little is known about the associations between its components and CKD. We conducted a nationwide cross-sectional study using the updated air pollution data in the nationwide population (N = 2,938,653). Using generalized additive models, we assessed the association between long-term exposure to PM2.5 and its components (i.e., black carbon [BC], organic matter [OM], nitrate [NO3-], ammonium [NH4+], sulfate [SO42-]), and CKD prevalence. The air pollution data was estimated using high-resolution and high-quality spatiotemporal datasets of ground-level air pollutants in China. Besides, we adopted a novel quantile-based g-computation approach to assess the effect of a mixture of PM2.5 constituents on CKD prevalence. The average concentration of PM2.5 was 78.67 ± 22.5 µg/m3, which far exceeded WHO AQG. In the fully adjusted generalized additive model, at a 10 km × 10 km spatial resolution, the ORs per IQR increase in previous 1-year average PM2.5 exposures was 1.380 (95%CI: 1.345-1.415), for NH4+ was 1.094 (95%CI: 1.062-1.126), for BC was 1.604 (95%CI: 1.563-1.646), for NO3- was 1.094 (95%CI: 1.060-1.130), for SO42- was 1.239 (95%CI: 1.208-1.272), and for the OM was 1.387 (95%CI: 1.354-1.421), respectively. Subgroup analysis showed females, younger, and healthier were more vulnerable to this effect. In the further exploration of the joint effect of PM2.5 compositions (OR 1.234 [95%CI 1.222-1.246]) per quartile increase in all 5 PM2.5 components, we found that PM2.5SO42- contributed the most. These findings provide important evidence for the positive relationship between long-term exposure to PM2.5 and its chemical constituents and CKD prevalence in a Chinese health check-up population, and identified PM2.5SO42- has the highest contribution to this relationship. This study provides clinical and public health guidance for reducing specific air particle exposure for those at risk of CKD.

Structural Analysis and Antioxidant and Immunoregulatory Activities of an Exopolysaccharide Isolated from Bifidobacterium longum subsp. longum XZ01.

Bifidobacterium longum subsp. longum XZ01 (BLSL1) is a new strain (isolated from the intestines of healthy people and deposited with the preservation number GDMCC 61618). An exopolysaccharide, S-EPS-1, was successfully isolated from the strain and then systematically investigated for the first time. Some structural features of S-EPS-1 were analyzed by chemical component, HPLC, ultraviolet, infrared, and nuclear magnetic resonance spectrum analyses. These analyses revealed that S-EPS-1 is a neutral heteropolysaccharide with an α-configuration. It contains mainly mannose and glucose, as well as small amounts of rhamnose and galactose. The molecular weight of S-EPS-1 was calculated to be 638 kDa. Several immunoregulatory activity assays indicated that S-EPS-1 could increase proliferation, phagocytosis, and NO production in vitro. In addition, S-EPS-1 could upregulate the expression of cytokines at the mRNA level through TLR4-mediated activation of the NF-κB signaling pathway in RAW 264.7 cells. Finally, S-EPS-1 was demonstrated to exhibit antioxidant activity by ABTS+• scavenging, DPPH• scavenging, and ferric-ion reducing power assays. Furthermore, S-EPS-1 can protect cells from oxidative stress and shows no cytotoxicity. These beneficial effects can be partly attributed to its antioxidant ability. Thus, the antioxidant S-EPS-1 may be applied as a functional food in the future.

[Observation of effect of Wu Yun Liu Qi on reproductive hormones in varicocele patients].

Objective： To observe roproductive hormone levels in varicocele patients during a cycle (6 years) of Wu Yun Liu Qi, and explore whether the cycle had effect on the roproductive hormone levels. Methods： Data of roproductive hormone levels in varicocele patients from 2015 to 2020 were analyzed retrospectively. FSH、LH、T、PRL、E2 levels and T/E2 ratio were compared among the six years. According to Chinese sexagenary cycle heavenly stems and earthly branches of each year from 2015 to 2020 its yunqi characteristics were determined. Results: Totally data of 848 cases of varicocele patients were collected from 2015 to 2020. Among which, in 2015 (Yiwei year) there were 57 cases, in 2016 (Bingshen year) 83 cases, in 2017 (Dingyou year ) 133 cases, in 2018(Wuxu year) 156 cases, in 2019(Sihai year) 274 cases, and in 2020(Gengzi year) 145 cases. The levels of FSH、LH、PRL、T were not diferrent statistically from the six years except individual year. However, the level of E2 in 2016 when the Yunqi was Shao Yang Xiang Huo Si Tian and Jue Yin Feng Mu Zai Quan obviously higher than other years excpet 2018( All P< 0.05). And T/E2 ratio was lower in 2016 than other years except 2018 and 2020( All P< 0.05). Conclusions: Shi Xiang factors of Wu Yun Liu Qi had effect on roproductive hormone levels in varicocele patients, showing by higher E2 level in Yinshen year when the Shi Xiang factors may have bad effect on human fertility.

Thrombin acts as inducer of proinflammatory macrophage migration inhibitory factor in astrocytes following rat spinal cord injury.

BACKGROUND: The danger-associated molecular patterns (DAMPs) are critical contributors to the progressive neuropathology and thereafter affect the functional outcomes following spinal cord injury (SCI). Up to now, the regulatory mechanisms on their inducible production from the living cells remain elusive, aside from their passive release from the necrotic cells. Thrombin is immediately activated by the damaged or stressed central nervous system (CNS), which potently mediates inflammatory astrocytic responses through proteolytic cleavage of protease-activated receptors (PARs). Therefore, SCI-activated thrombin is conceived to induce the production of DAMPs from astrocytes at lesion site. METHODS: Rat SCI model was established by the cord contusion at T8-T10. The expression of thrombin and macrophage migration inhibitory factor (MIF) was determined by ELISA and Western blot. The PAR1, PAR3, and PAR4 receptors of thrombin were examined by PCR and immunohistochemistry. Primary astrocytes were isolated and purified from the spinal cord, followed by stimulation with different concentrations of thrombin either for transcriptome sequencing or for analysis of thrombin-mediated expression of MIF and related signal pathways in the presence or absence of various inhibitors. The post-injury locomotor functions were assessed using the Basso, Beattie, and Bresnahan (BBB) locomotor scale. RESULTS: MIF protein levels were significantly elevated in parallel with those of thrombin induced by SCI. Immunostaining demonstrated that PAR1 receptor, together with MIF, was abundantly expressed in astrocytes. By transcriptome sequencing and bioinformatical analysis of thrombin-stimulated primary astrocytes, MIF was identified to be dynamically regulated by the serine protease. Investigation of the underlying mechanism using various inhibitors revealed that thrombin-activated PAR1 was responsible for the MIF production of astrocytes through modulation of JNK/NFκB pathway. Administration of PAR1 inhibitor at lesion sites following SCI significantly reduced the protein levels of MIF and ameliorated functional deficits of rat locomotion. CONCLUSION: SCI-activated thrombin is a robust inducer of MIF production from astrocytes. Exploring the roles of thrombin in promoting the production of DAMPs from astrocytes at lesion site will provide an alternative strategy for the clinical therapy of CNS inflammation.

Terahertz metasurface with multiple BICs/QBICs based on a split ring resonator.

Bound state in the continuum (BIC) refers to the trapped state in the radiation continuum of a system. In the terahertz band, BIC provides a unique and feasible method to design devices with ultra-high quality factor (Q factor) and to achieve intense terahertz-matter interaction, which is of great value to terahertz science and technology. Here, multiple BICs protected by the resonance symmetry in the terahertz metasurface consisting of metallic split ring resonators (SRR) is demonstrated. The evolution from the BIC to the quasi-BIC (QBIC) is induced by changing the gap width of the SRRs. The proposed BICs are experimentally demonstrated and analyzed by the coupled mode theory along with the numerical simulation. It is found that the leakage behavior of these QBICs is strongly affected by the intrinsic Ohmic loss in the SRRs while it is quite robust to the tilted incidence.

Association Between Lipid Profiles and Left Ventricular Hypertrophy: New Evidence from a Retrospective Study.

Objective To explore the association between lipid profiles and left ventricular hypertrophy in a Chinese general population. Methods We conducted a retrospective observational study to investigate the relationship between lipid markers [including triglycerides, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein (HDL) cholesterol, non-HDL-cholesterol, apolipoprotein A-I, apolipoprotein B, lipoprotein[a], and composite lipid profiles] and left ventricular hypertrophy. A total of 309,400 participants of two populations (one from Beijing and another from nationwide) who underwent physical examinations at different health management centers between 2009 and 2018 in China were included in the cross-sectional study. 7,475 participants who had multiple physical examinations and initially did not have left ventricular hypertrophy constituted a longitudinal cohort to analyze the association between lipid markers and the new-onset of left ventricular hypertrophy. Left ventricular hypertrophy was measured by echocardiography and defined as an end-diastolic thickness of the interventricular septum or left ventricle posterior wall > 11 mm. The Logistic regression model was used in the cross-sectional study. Coxmodel and Coxmodel with restricted cubic splines were used in the longitudinal cohort. Results In the cross-sectional study, for participants in the highest tertile of each lipid marker compared to the respective lowest, triglycerides [odds ratio (OR): 1.250, 95%CI: 1.060 to 1.474], HDL-cholesterol (OR: 0.780, 95%CI: 0.662 to 0.918), and lipoprotein(a) (OR: 1.311, 95%CI: 1.115 to 1.541) had an association with left ventricular hypertrophy. In the longitudinal cohort, for participants in the highest tertile of each lipid marker at the baseline compared to the respective lowest, triglycerides [hazard ratio (HR): 3.277, 95%CI: 1.720 to 6.244], HDL-cholesterol (HR: 0.516, 95%CI: 0.283 to 0.940), non-HDL-cholesterol (HR: 2.309, 95%CI: 1.296 to 4.112), apolipoprotein B (HR: 2.244, 95%CI: 1.251 to 4.032) showed an association with new-onset left ventricular hypertrophy. In the Coxmodel with forward stepwise selection, triglycerides were the only lipid markers entered into the final model. Conclusion Lipids levels, especially triglycerides, are associated with left ventricular hypertrophy. Controlling triglycerides level potentiate to be a strategy in harnessing cardiac remodeling but deserve to be further investigated.

Global and Regional Trends and Projections of Infective Endocarditis-Associated Disease Burden and Attributable Risk Factors from 1990 to 2030.

Objective To forecast the future burden and its attributable risk factors of infective endocarditis (IE). Method We analyzed the disease burden of IE and its risk factors from 1990 to 2019 using the Global Burden of Disease 2019 database and projected the disease burden from 2020 to 2030 using a Bayesian age-period-cohort model. Results By 2030, the incidence of IE will increase uncontrollably on a global scale, with developed countries having the largest number of cases and developing countries experiencing the fastest growth. The affected population will be predominantly males, but the gender gap will narrow. The elderly in high-income countries will bear the greatest burden, with a gradual shift to middle-income countries. The incidence of IE in countries with middle/high-middle social-demographic indicators (SDI) will surpass that of high SDI countries. In China, the incidence rate and the number of IE will reach 18.07 per 100,000 and 451,596 in 2030, respectively. IE-associated deaths and heart failure will continue to impose a significant burden on society, the burden on women will increase and surpass that on men, and the elderly in high-SDI countries will bear the heaviest burden. High systolic blood pressure has become the primary risk factor for IE-related death. Conclusions This study provides comprehensive analyses of the disease burden and risk factors of IE worldwide over the next decade. The IE-associated incidence will increase in the future and the death and heart failure burden will not be appropriately controlled. Gender, age, regional, and country heterogeneity should be taken seriously to facilitate in making effective strategies for lowering the IE disease burden.

Genome Sequence Resource for Erysiphe necator NAFU1, a Grapevine Powdery Mildew Isolate Identified in Shaanxi Province of China.

Erysiphe necator is an economically important biotrophic fungal pathogen responsible for powdery mildew disease on grapevine. Currently, genome sequences are available for only a few E. necator isolates from the United States. Based on the combination of Nanopore and Illumina sequencing technologies, we present here the complete genome assembly for an isolate of E. necator, NAFU1, identified in China. We acquired a total of 15.93 Gb of raw reads. These reads were processed into a 61.12-Mb genome assembly containing 73 contigs with an N50 of 2.06 Mb and a maximum length of 6.05 Mb. Combining the results of three gene-prediction modules (i.e., an evidence-based gene modeler [EVidenceModeler], an ab initio gene modeler, and a homology-based gene modeler), we predicted 7,235 protein-coding genes in the assembled genome of E. necator NAFU1. This information will facilitate studies of genome evolution and pathogenicity mechanisms of E. necator and other powdery mildew species through comparative genome sequence analysis and other molecular genetic tools.[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

D-dopachrome tautomerase activates COX2/PGE2 pathway of astrocytes to mediate inflammation following spinal cord injury.

BACKGROUND: Astrocytes are the predominant glial cell type in the central nervous system (CNS) that can secrete various cytokines and chemokines mediating neuropathology in response to danger signals. D-dopachrome tautomerase (D-DT), a newly described cytokine and a close homolog of macrophage migration inhibitory factor (MIF) protein, has been revealed to share an overlapping function with MIF in some ways. However, its cellular distribution pattern and mediated astrocyte neuropathological function in the CNS remain unclear. METHODS: A contusion model of the rat spinal cord was established. The protein levels of D-DT and PGE2 synthesis-related proteinase were assayed by Western blot and immunohistochemistry. Primary astrocytes were stimulated by different concentrations of D-DT in the presence or absence of various inhibitors to examine relevant signal pathways. The post-injury locomotor functions were assessed using the Basso, Beattie, and Bresnahan (BBB) locomotor scale. RESULTS: D-DT was inducibly expressed within astrocytes and neurons, rather than in microglia following spinal cord contusion. D-DT was able to activate the COX2/PGE2 signal pathway of astrocytes through CD74 receptor, and the intracellular activation of mitogen-activated protein kinases (MAPKs) was involved in the regulation of D-DT action. The selective inhibitor of D-DT was efficient in attenuating D-DT-induced astrocyte production of PGE2 following spinal cord injury, which contributed to the improvement of locomotor functions. CONCLUSION: Collectively, these data reveal a novel inflammatory activator of astrocytes following spinal cord injury, which might be beneficial for the development of anti-inflammation drug in neuropathological CNS.

Analysis of tectonic geochemical characteristics and leaching effects of typical pollutants in Kongyu gold mining area in Dadu River Basin, Kangding.

Kongyu Gold Mining Area is located in the northern margin of the Sichuan-Yunnan tectonic belt. This area has gone through two large tectonic cycles of Mesoproterozoic, Neoproterozoic and Phanerozoic. The strata are accompanied by a large number of tensile cracks, shear cracks and microfissures. The voidage, permeability and transitional effect of the rock are increased, and the transformation between surface water and groundwater is enhanced. On the other hand, tectonic movement controls the distributions and allocations of elements in the earth's crust, resulting in directional geochemical changes in crustal materials and rules. Driven by the tectonic force, the elements are reallocated. The ion content and ion compressibility of those elements increase and decrease inversely. The manifestations of rocks and minerals under directional pressure can be characterized by the flow and puncture of plastic minerals and the fragmentation of hard and brittle minerals. In the process of leaching, the pollutant elements precipitate from the deposits of different granular ores, and most are absorbed by the soil column; thus, the mass fraction of polluting elements in the soil column obviously increases. The variability is the largest when the leachate passes through the fine ore. The rate of change of the element mass fraction from high to low is Ni, Zn, Cu, Cd, Pb, As and Cr. A small part migrated from the soil column to the collection fluid, and the leaching effect is related to the rate of change of soil mass fraction, the ion radius of elements and the compressibility.

[Effect of bilateral microsurgical subinguinal varicocelectomy on asthenozoospermia and oligozoospermia: A report of 109 cases].

OBJECTIVE: To investigate the effects of bilateral microsurgical subinguinal varicocelectomy (BMSV) in patients with asthenozoospermia or oligozoospermia. METHODS: Totally 147 patients with male infertility received BMSV from January 2018 to May 2019, of whom 109 had complete data recorded. We retrospectively analyzed the clinical data, including the total sperm count per ejeculate, sperm concentration and sperm motility before and after surgery, and the rate of natural conception achieved during the follow-up. RESULTS: BMSV achieved a total effectiveness rate of 79.00% in improving the percentage of progressively motile sperm (a rise of ≥20%) and a marked effectiveness rate of 70.00% (a rise of ≥50%) in the 100 cases of asthenozoospermia as compared with the baseline, with a mean recovery time of (110.13 ± 37.43) days. Besides, a total effectiveness rate of 74.29% (an increase of ≥20%) and a marked effectiveness rate of 71.43% (an increase of ≥50%) were attained in the improvement of sperm concentration in the 35 cases of oligozoospermia, with a mean recovery time of (117.00 ± 48.79 ) days. A natural conception rate of 30.30% was observed during the follow-up. No severe adverse events occurred postoperatively. CONCLUSIONS: BMSV is significantly effective for the treatment of asthenozoospermia and oligozoospermia.

One-Step Preparation of Tough and Self-Healing Polyion Complex Hydrogels with Tunable Swelling Behaviors.

Polyion complex (PIC) hydrogels formed by charge attraction of opposite charged polymers have received unique research interest. Their conventional preparation method, with a large amount of residual salt after polymerization, requires a long-term dialysis treatment to remove the salt and toughen the gel. Here, a promising strategy for the one-step preparation of tough PIC hydrogels without dialysis after polymerization is provided. Bicarbonate and proton ions are selected as the counter ions of the cationic monomer and anionic polymers, respectively. By a CO2 -generating reaction between the counter ions, the residual salt is removed before polymerization, and thus, a PIC hydrogel with tough mechanical performance can be obtained instantly without dialysis. Due to the absence of dialysis, the tough hydrogel can be formed with a wide range of ratios for the oppositely charged polymer with distinct swelling behaviors from non-swelling to super-swelling. This tunable swelling behavior shows the possibility for shape-morphing systems from this one-step method.

The Plasma LncRNA Acting as Fingerprint in Hilar Cholangiocarcinoma.

BACKGROUND & AIMS: Current studies have indicated that long non-coding RNAs (lncRNAs) could act as tumor biomarkers for disease diagnosis and prognosis prediction. In this study, we mainly focused on determining the expression of circulating lncRNAs in patients suffering for hilar cholangiocarcinoma (HC), aiming to reveal the potential lncRNA as a fingerprint. METHODS: A total 12 lncRNAs were previously proven to be aberrantly expressed in HC tumor tissues. All of the 12 lncRNAs were selected as candidate targets for subsequent circulating lncRNA assay. The candidate lncRNAs were validated by qRT-PCR arranged in training and validation sets. The risk score analysis was employed. Data was presented with receiver operating characteristic curve (ROC). RESULTS: Circulating PCAT1, MALAT1, and CPS1-IT1 were significantly increased in plasma samples of HC patients in both the training set and validation set. Through ROC analysis, we found that the three plasmatic lncRNAs presented the area under ROC curve value (AUC) as 0.784, 0.860, and 0.677. Further combination with the three factors indicated a higher power (AUC, 0.893; sensitivity, 85.5%; specificity, 93.2%). CONCLUSION: This was the first time to reveal the potential circulating fingerprints for predicting HC. PCAT1, MALAT1, and CPS1-IT1 may act as novel early diagnosis biomarkers for predicting HC.