Background and purpose
Previous studies suggested that the overall burden of prior infections contributes to cardiovascular diseases and stroke. In the present study, the association between ...infectious burden (IB) and Alzheimer's disease (AD) was examined.
Methods
Antibody titers to common infectious pathogens including cytomegalovirus (CMV), herpes simplex virus type 1 (HSV‐1), Borrelia burgdorferi, Chlamydophila pneumoniae and Helicobacter pylori were measured by enzyme‐linked immunosorbent assay in 128 AD patients and 135 healthy controls. IB was defined as a composite serological measure of exposure to these common pathogens.
Results
Seropositivities toward zero−two, three and four−five of these pathogens were found in 44%, 40% and 16% of healthy controls but in 20%, 44% and 36% of AD patients, respectively. IB, bacterial burden and viral burden were independently associated with AD after adjusting for age, gender, education, APOE genotype and various comorbidities. Mini‐Mental State Examination scores were negatively correlated with IB in all cases. Serum beta‐amyloid protein (Aβ) levels (i.e. Aβ40, Aβ42 and total Aβ) and inflammatory cytokines (i.e. interferon‐γ, tumor necrosis factor α, interleukin‐1β and interleukin‐6) in individuals exposed to four−five infectious pathogens were significantly higher than those exposed to zero−two or three pathogens.
Conclusions
IB consisting of CMV, HSV‐1, B. burgdorferi, C. pneumoniae and H. pylori is associated with AD. This study supports the role of infection/inflammation in the etiopathogenesis of AD.
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Summary
Background
Vitiligo is an autoimmune chronic depigmentation disorder caused by melanocyte loss. Previous studies found that CD4+CD25+ regulatory T‐cell (Treg) dysfunction was involved in the ...pathogenesis of vitiligo and that gene polymorphisms in forkhead box P3 (FOXP3) – a master regulator of Treg development and function – were associated with susceptibility to some autoimmune disorders. Therefore, we hypothesized that functional polymorphisms of the FOXP3 gene might be associated with vitiligo via dysregulation of Treg cells.
Objectives
To evaluate whether FOXP3 polymorphisms are associated with vitiligo risk.
Material and methods
In this hospital‐based case–control study of 682 patients with vitiligo and 682 vitiligo‐free age‐ and sex‐matched controls, we genotyped three single nucleotide polymorphisms (SNPs) of the FOXP3 gene – rs2232365, rs3761548 and rs5902434 – by performing polymerase chain reaction with sequence‐specific primers (PCR‐SSP).
Results
Significantly increased vitiligo risk was associated with the rs2232365 GG odds ratio (OR) 1·68, 95% confidence interval (CI) 1·17–2·39, P = 0·004 and rs3761548 AA (OR 1·82, 95% CI 1·10–3·01, P = 0·033) genotypes compared with the rs2232365 AA and rs3761548 CC genotypes. On combined analysis of these three variant alleles, we found that individuals carrying 2–6 variant alleles had significantly increased vitiligo risk (OR 1·34, 95% CI 1·08–1·66). This risk was more pronounced in the following subgroups: age > 20 years, male sex, active vitiligo, nonsegmental vitiligo and other accompanying autoimmune diseases.
Conclusions
FOXP3 gene polymorphisms contributed to vitiligo risk in a Han Chinese population.
What's already known about this topic?
Previous findings have suggested that forkhead box P3 (FOXP3) is a master regulator of regulatory T cells (Tregs) for maintaining immune tolerance and abrogating autoimmune diseases.
Dysfunction of Tregs is involved in the autoimmune mechanism of vitiligo.
FOXP3 polymorphisms negatively affect the expression and functions of FOXP3 as well as of its target genes.
What does this study add?
Our study suggests an association between FOXP3 gene polymorphisms and vitiligo susceptibility.
ABSTRACT
High time resolution and accuracy are of critical importance in the studies of timing analysis and time delay localization of gamma-ray bursts (GRBs), soft gamma-ray repeaters (SGRs) and ...pulsars. The Gravitational wave high-energy Electromagnetic Counterpart All-sky Monitor (GECAM) consisting of two micro-satellites, GECAM-A and GECAM-B, launched on 2020 December 10, is aimed at monitoring and locating X-ray and GRBs all over the sky. To achieve its scientific goals, GECAM is designed to have the highest time resolution (0.1 $\mu {\rm s}$) among all GRB detectors ever flown. Here, we make a comprehensive time calibration campaign including both on-ground and on-orbit tests to derive not only the relative time accuracy of GECAM satellites and detectors, but also the absolute time accuracy of GECAM-B. Using the on-ground calibration with a $\rm ^{22}Na$ radioactive source, we find that the relative time accuracy between GECAM-A and GECAM-B is about 0.15 $\mu {\rm s}$ (1σ). To measure the relative time accuracy between all detectors of a single GECAM satellite, cosmic-ray events detected on orbit are utilized since they could produce many secondary particles simultaneously record by multiple detectors. We find that the relative time accuracy among all detectors onboard GECAM-B is about 0.12 $\mu {\rm s}$ (1σ). Finally, we use the novel Li-CCF method to perform the absolute time calibration with Crab pulsar and SGR J1935+2154, both of which were jointly observed by GECAM-B and Fermi/GBM, and obtain that the time difference between GECAM-B and Fermi/GBM is 3.06 ± 6.04 $\mu {\rm s}$ (1σ).
The Tibetan Plateau is the highest and one of the most demanding environments ever inhabited by humans. We investigated the timing and mechanisms of its initial colonization at the Nwya Devu site, ...located nearly 4600 meters above sea level. This site, dating from 40,000 to 30,000 years ago, is the highest Paleolithic archaeological site yet identified globally. Nwya Devu has yielded an abundant blade tool assemblage, indicating hitherto-unknown capacities for the survival of modern humans who camped in this environment. This site deepens the history of the peopling of the "roof of the world" and the antiquity of human high-altitude occupations more generally.
To investigate the characteristics of the laryngeal mucosal microvascular network in suspected laryngeal cancer patients, using narrow band imaging, and to evaluate the value of narrow band imaging ...endoscopy in the early diagnosis of laryngeal precancerous and cancerous lesions.
Eighty-five consecutive patients with suspected precancerous or cancerous laryngeal lesions were enrolled in the study. Endoscopic narrow band imaging findings were classified into five types (I to V) according to the features of the mucosal intraepithelial papillary capillary loops assessed.
A total of 104 lesions (45 malignancies and 59 nonmalignancies) was detected under white light and narrow band imaging modes. The sensitivity and specificity of narrow band imaging in detecting malignant lesions were 88.9 and 93.2 per cent, respectively. The intraepithelial papillary capillary loop classification, as determined by narrow band imaging, was closely associated with the laryngeal lesions' histological findings. Type I to IV lesions were considered nonmalignant and type V lesions malignant. For type Va lesions, the sensitivity and specificity of narrow band imaging in detecting severe dysplasia or carcinoma in situ were 100 and 79.5 per cent, respectively. In patients with type Vb and Vc lesions, the sensitivity and specificity of narrow band imaging in detecting invasive carcinoma were 83.8 and 100 per cent, respectively.
Narrow band imaging is a promising approach enabling in vivo differentiation of nonmalignant from malignant laryngeal lesions by evaluating the morphology of mucosal capillaries. These results suggest endoscopic narrow band imaging may be useful in the early detection of laryngeal cancer and precancerous lesions.
The viral spike (S) protein on the surface of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds to angiotensin-converting enzyme 2 (ACE2) receptors on the host cells, ...facilitating its entry and infection. Here, functionalized nanofibers targeting the S protein with peptide sequences of IRQFFKK, WVHFYHK and NSGGSVH, which are screened from a high-throughput one-bead one-compound screening strategy, are designed and prepared. The flexible nanofibers support multiple binding sites and efficiently entangle SARS-CoV-2, forming a nanofibrous network that blocks the interaction between the S protein of SARS-CoV-2 and the ACE2 on host cells, and efficiently reduce the invasiveness of SARS-CoV-2. In summary, nanofibers entangling represents a smart nanomedicine for the prevention of SARS-CoV-2.
It is well established that the tumor suppressor p53 plays major roles in regulating apoptosis and cell cycle progression. In addition, recent studies have demonstrated that p53 is actively involved ...in regulating cell differentiation in muscle, the circulatory system and various carcinoma tissues. We have recently shown that p53 also controls lens differentiation. Regarding the mechanism, we reveal that p53 directly regulates c-Maf and Prox1, two important transcription factors to control cell differentiation in the ocular lens. In the present study, we present further evidence to show that p53 can regulate lens differentiation by controlling expression of the differentiation genes coding for the lens crystallins. First, the αA and βA3/A1 gene promoters or introns all contain putative p53 binding sites. Second, gel mobility shifting assays revealed that the p53 protein in nuclear extracts from lens epithelial cells directly binds to the p53 binding sites found in these crystallin gene promoters or introns. Third, exogenous wild type p53 induces dose-dependent expression of the luciferase reporter gene driven by different crystallin gene promoters and the exogenous dominant negative mutant p53 causes dose-dependent inhibition of the same crystallin genes. Fourth, ChIP assays revealed that p53 binds to crystallin gene promoters in vivo. Finally, in the p53 knockout mouse lenses, expression levels of various crystallins were found down-regulated in comparison with those from the wild type mouse lenses. Together, our results reveal that p53 directly regulates expression of different sets of genes to control lens differentiation.
The waste Nd–Fe–B sintered magnets up to 500 kg per batch were recycled to manufacture anisotropic sintered magnets by combination of hydrogen decrepitation (HD) and alloying technique. Magnetic ...properties and thermal stability of both the waste magnets and recycled magnets were investigated. The recycled magnet exhibits magnetic properties with remanence (Br) of 12.38 kGs, coercivity (Hci) of 24.89 kOe, and maximum energy product (BH)max of 36.51 MGOe, respectively, which restores 99.20% of Br, 105.65% of Hci, and 98.65% of (BH)max of the waste magnets, respectively. The volume fraction of Nd-rich phase in the recycled magnets is about 10.1 vol.%, which is bigger than that of the waste magnets due to the additive of Nd3PrFe14B alloy containing more rare earth. The remanence temperature coefficient (α) and coercivity temperature coefficient (β) of the recycled magnets are −0.1155%/K and −0.5099%/K in the range of 288–423 K, respectively, which are comparative to those of the waste magnets.
•Large batch recycling of waste Nd–Fe–B sintered magnets were performed.•The recycled magnet restores 99.20% of Br, 105.65% of Hci and 98.65% of (BH)max of the magnet.•The recycled magnets bears bigger volume fraction and better distribution of Nd-rich phase.•The recycled magnets exhibit similar temperature coefficients and maximum working temperature.
We hypothesize that chemical toxicity to marine ectotherms is the lowest at an optimum temperature (OT) and it exacerbates with increasing or decreasing temperature from the OT. This study aimed to ...verify this hypothetical temperature-dependent chemical toxicity (TDCT) model through laboratory experiments. Acute toxicity over a range of temperatures was tested on four commonly used chemicals to three marine ectotherms. Our results confirmed that toxicities, in terms of 96-h LC50 (median lethal concentration; for the marine medaka fish
Oryzias melastigma
and the copepod
Tigriopus japonicus
) and 24-h LC50 (for the rotifer
Brachionus
koreanus
), were highly temperature-dependent, and varied between test species and between study chemicals. The LC50 value of the fish peaked at 20 °C for copper (II) sulphate pentahydrate and triphenyltin chloride, and at 25 °C for dichlorophenyltrichloroethane and copper pyrithione, and decreased with temperature increase or decrease from the peak (i.e., OT). However, LC50 values of the copepod and the rotifer generally showed a negative relationship with temperature across all test chemicals. Both copepod and rotifer entered dormancy at the lowest temperature of 4 °C. Such metabolic depression responses in these zooplanktons could reduce their uptake of the chemical and hence minimize the chemical toxicity at low temperatures. Our TDCT model is supported by the fish data only, whereas a simple linear model fits better to the zooplankton data. Such species-specific TDCT patterns may be jointly ascribed to temperature-mediated changes in (1) the physiological response and susceptibility of the marine ectotherms to the chemical, (2) speciation and bioavailability of the chemical, and (3) toxicokinetics of the chemical in the organisms.
Summary
Background Vitiligo is an acquired depigmentation disorder resulting from selective destruction of melanocytes. The aryl hydrocarbon receptor (AHR) is vital to the regulation of ...melanogenesis and melanocyte proliferation and differentiation through modulating the expressions of melanogenesis‐related genes. AHR mutations may negatively affect AHR proteins and its target genes. Therefore, we hypothesized that AHR polymorphisms might be involved in vitiligo by impacting the transcriptional activities of related genes as mentioned above.
Objectives To evaluate the potential association between AHR polymorphisms and vitiligo susceptibility.
Methods We performed a hospital‐based, case–control study of 1000 patients with vitiligo and 1000 vitiligo‐free but age‐ and gender‐matched controls. Two single nucleotide polymorphisms of the AHR gene (rs10249788 and rs2066853) were selected and genotyped using a polymerase chain reaction–restriction fragment length polymorphism method.
Results A statistically significantly decreased risk of vitiligo was found to be associated with the TT and CT genotypes of rs10249788 odds ratio (OR) 0·59, 95% confidence interval (CI) 0·38–0·93; P = 0·028 and OR 0·82, 95% CI 0·68–0·98; P = 0·032, respectively as well as among subgroups: male, active, nonsegmental vitiligo, and onset age ≤ 20 years. Moreover, subjects with the combined (CT + TT)/GG genotype or T/G haplotype (rs10249788/rs2066853) showed a decreased risk for vitiligo (OR 0·57, 95% CI 0·37–0·87, P = 0·009 and OR 0·78, 95% CI 0·64–0·96, P = 0·033, respectively).
Conclusions These results suggest that the T allele of rs10249788 located in the promoter of the AHR gene is associated with a protective effect on vitiligo in Han Chinese populations.
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