Clostridium difficile toxin B (TcdB) is a critical virulence factor that causes diseases associated with C. difficile infection. Here we carried out CRISPR-Cas9-mediated genome-wide screens and ...identified the members of the Wnt receptor frizzled family (FZDs) as TcdB receptors. TcdB binds to the conserved Wnt-binding site known as the cysteine-rich domain (CRD), with the highest affinity towards FZD1, 2 and 7. TcdB competes with Wnt for binding to FZDs, and its binding blocks Wnt signalling. FZD1/2/7 triple-knockout cells are highly resistant to TcdB, and recombinant FZD2-CRD prevented TcdB binding to the colonic epithelium. Colonic organoids cultured from FZD7-knockout mice, combined with knockdown of FZD1 and 2, showed increased resistance to TcdB. The colonic epithelium in FZD7-knockout mice was less susceptible to TcdB-induced tissue damage in vivo. These findings establish FZDs as physiologically relevant receptors for TcdB in the colonic epithelium.
Full text
Available for:
IJS, KISLJ, NUK, SBMB, UL, UM, UPUK
Several recent papers have reported strong signals of selection on European polygenic height scores. These analyses used height effect estimates from the GIANT consortium and replication studies. ...Here, we describe a new analysis based on the the UK Biobank (UKB), a large, independent dataset. We find that the signals of selection using UKB effect estimates are strongly attenuated or absent. We also provide evidence that previous analyses were confounded by population stratification. Therefore, the conclusion of strong polygenic adaptation now lacks support. Moreover, these discrepancies highlight (1) that methods for correcting for population stratification in GWAS may not always be sufficient for polygenic trait analyses, and (2) that claims of differences in polygenic scores between populations should be treated with caution until these issues are better understood.
This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (see decision letter).
Long noncoding RNAs (lncRNAs) play crucial roles in tumorigenesis. However, the mechanisms of most lncRNAs in cancers are largely unknown. Because the RNA component of mitochondrial RNA processing ...endoribonuclease (RMRP) is one of the dysregulated lncRNAs in gastric cancer, this study explored its molecular mechanisms in carcinogenesis. RMRP levels in 792 tissues, plasma and gastric juices from patients with various stages of gastric tumorigenesis were analyzed by quantitative reverse transcription-polymerase chain reaction. Overexpression and RNA interference were used to manipulate RMRP expression by RMRP expression vector and small interfering RNAs, respectively. Its mechanisms were evaluated by flow cytometry, real-time cell analysis, plate colony formation assays, and xenograft models. RMRP levels in tissue, plasma and gastric juices from patients with gastric cancer were significantly different from those from controls. Its levels were significantly associated with Borrmann type and metastasis. Plasma and gastric juice RMRP had higher sensitivity and specificity than commonly used markers (such as carcinoembryonic antigen and carbohydrate antigen 19-9). Knockdown of RMRP significantly inhibited cell proliferation in vitro and in vivo, whereas overexpression of RMRP promoted cell growth. Acting as a miR-206 sponge, RMRP modulated cell cycle by regulating Cyclin D2 expression. RMRP plays a crucial role in gastric cancer occurrence and can be used as a novel biomarker for gastric cancer.
The global coronavirus disease 2019 (COVID-19) pandemic has led to a health crisis. It remains unclear how anxiety affects blood pressure (BP) and cardiovascular risk among older patients with ...hypertension. In this study, we extracted longitudinal data on home BP monitored via a smartphone-based application in 3724 elderly patients with hypertension from a clinical trial (60-80 years; 240 in Wuhan and 3484 in non-Wuhan areas) to examine changes in morning BP during the COVID-19 outbreak in China. Anxiety was evaluated using Generalized Anxiety Disorder-7 item scores. Changes in morning systolic BP (SBP) were analyzed for five 30-day periods during the pandemic (October 21, 2019 to March 21, 2020), including the pre-epidemic, incubation, developing, outbreak, and plateau periods. Data on cardiovascular events were prospectively collected for one year. A total of 262 individuals (7.0%) reported an increased level of anxiety, and 3462 individuals (93.0%) did not. Patients with anxiety showed higher morning SBP than patients without anxiety, and the between-group differences in SBP change were +1.2 mmHg and +1.7 mmHg during the outbreak and plateau periods (P < 0.05), respectively. The seasonal BP variation in winter among patients with anxiety was suppressed during the pandemic. Anxious patients had higher rates of uncontrolled BP. During the 1-year follow-up period, patients with anxiety had an increased risk of cardiovascular events with a hazard ratio of 2.47 (95% confidence interval, 1.10-5.58; P = 0.03). In summary, COVID-19-related anxiety was associated with a short-term increase in morning SBP among older patients and led to a greater risk of cardiovascular events. (ClinicalTrials. gov number, NCT03015311).
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
•miR-218 expression is downregulated in prostate cancer.•miR-218 inhibits prostate tumor cells proliferation partially through promoting apoptosis.•miR-218 targets TPD52 by binding to its ...3′-UTR.•miR-218 suppresses prostate cancer cell growth through inhibiting TPD52 expression.
The tumor protein D52 (TPD52) is an oncogene overexpressed in prostate cancer (PC) due to gene amplification. Although the oncogenic effect of TPD52 is well recognized, how its expression is regulated is still not clear. This study tried to explore the regulative role of miR-218, a tumor suppressing miRNA on TPD52 expression and prostate cancer cell proliferation. We found the expression of miR-218 was significantly lower in PC specimens. Based on gain and loss of function analysis, we found miR-218 significantly inhibit cancer cell proliferation by inducing apoptosis. These results strongly suggest that miR-218 plays a tumor suppressor role in PC cells. In addition, our data firstly demonstrated that miR-218 directly regulates oncogenic TPD52 in PC3 cells and the miR-218-TPD52 axis can regulate growth of this prostate cancer cell line. Knockdown of TPD52 resulted in significantly increased cancer cell apoptosis. Clearly understanding of oncogenic TPD52 pathways regulated by miR-218 might be helpful to reveal new therapeutic targets for PC.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The Da Vinci Robot is the most advanced micro-control system in endoscopic surgical instruments and has gained a lot of valuable experience today. However, the technical feasibility and oncological ...safety of the robot over open surgery are still uncertain. This work is to systematically evaluate the efficacy of the unilateral axillary approach for robotic surgery compared to open surgery for differentiated thyroid carcinoma.
PubMed, Embase, Cochrane Library, and Web of Science databases were utilized to search for relevant literatures of robotic thyroid surgery using unilateral axillary approach compared to open thyroid surgery, and a meta-analysis was performed using RevMan software version 5.3. Statistical analysis was performed through Mantle-Haenszel and inverse variance methods.
Twelve studies with a total of 2660 patients were included in the meta-analysis. The results showed that compared with the open group, the robotic group had a longer total thyroidectomy time, shorter hospital stay, less intraoperative bleeding, more postoperative drainage, fewer retrieved central lymph nodes, and higher cosmetic satisfaction (all P < 0.05). In contrast, temporary and permanent laryngeal recurrent nerve injury, temporary and permanent hypoparathyroidism or hypocalcemia, brachial plexus nerve injury, number of retrieved central lymph nodes, number of retrieved lymph nodes in the lateral cervical region, number of lymph node metastases in the lateral cervical region, hematoma, seroma, lymphatic leak, stimulated thyroglobulin (sTg) and unstimulated thyroglobulin (uTg), and the number and recurrence rate of patients with sTg <1ng/ml were not statistically different between the two groups (P > 0.05).
The unilateral axillary approach for robotic thyroid surgery may achieve outcomes similar to those of open surgery. Further validation is required in a prospective randomized controlled trial.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
8.
Nonappearance and Procedural Delicacy ZHANG, Xinjun
The Journal of International Law and Diplomacy,
2018/08/20, Volume:
117, Issue:
2
Journal Article
Tapejaridae is a clade of toothless pterosaurs typically characterized by a large nasoantorbital fenestra and a premaxillary crest that extends from the anterior to the posterior part of the skull. ...Sinopterus dongi was the first reported Chinese tapejarid. Another genus "Huaxiapterus" was described, but it was later on determined that "Huaxiapterus" is in fact an invalid name. Here, we report on a new juvenile specimen of Sinopterus atavismus from the Jiufotang Formation of western Liaoning, China, and revise the diagnosis of this species. Sinopterus atavismus does not present a square-like crest. Moreover the feature that groove in the ventral part of the second or third phalanx of manual digit IV is not diagnostic of the species. In the new material, the skull preserves a pointed process in the middle part of the dorsal margin of the premaxillary crest, which is different from other Chinese tapejarids. Considering the new specimen is known from a large skeleton that differed from the holotype, this difference may be related to ontogeny, as the premaxillary crest of the holotype is short and does not extend as long as that of the new specimen.
Abstract
Revealing the effects of drought stress on the photosynthetic characteristics and yield of naked oats (
Avena nuda
L.) is significant for enhancing the productivity of oats. In this study, a ...potted experiment consisting of four water levels was conducted in the Bashang area of Hebei Province, China. The drought stress period was established as the continual 8 days during the jointing-heading stage. The aims were to reveal the impacts of drought stress on the photosynthetic characteristics and yield of naked oats during the critical stage. The results showed that the photosynthetic rate (
P
n
), transpiration rate (
T
r
), and stomatal conductance (
G
s
) decreased under all conditions of drought stress. The intercellular CO
2
concentration (
C
i
) decreased under light drought stress, while it increased under moderate and severe drought stress. The initial chlorophyll fluorescence rate (
F
o
) increased by 9.03–50.92% under drought stress, and the maximum fluorescence rate (
F
m
) decreased by 8.49–19.73% under drought stress. The photochemical efficiency (
F
v
/
F
m
) increased by 10.37–24.12% under drought stress. The yields decreased by 9.5–12.7%, 16.8–27.0% and 44.1–47.7% under light, moderate and severe drought stress during the critical stage, respectively. The grains per panicle decreased by 1.7–12.5%, 8.3–24.3% and 32.7–34.2% under light, moderate and severe drought stress conditions, respectively. The 1000-grain weight decreased by 5.7–8.6%, 12.7–14.5% and 16.8–19.1% under light, moderate and severe drought stress conditions, respectively. The panicle numbers did not vary significantly among the different drought stress treatments. The photosynthetic rate, stomatal conductance and transpiration all had significant positive relationships with the yield of naked oat (
P
< 0.01). Parameters of PS II except for
F
o
all had significant positive relationships with the yield of naked oats (
P
< 0.05). This study is significant for enhancing the production efficiency of naked oat under drought stress.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
PDF
