The incidence of early-onset colorectal cancer (CRC) is increasing. Many guidelines recommend initiating screening at 45 years. This study investigated the detection rate of advanced colorectal ...neoplasm (ACRN) by using fecal immunochemical tests (FITs) in individuals aged 40-49 years.
PubMed, Embase, and Cochrane Library databases were searched from inception to May 2022. The primary outcomes were the detection rates and positive predictive values of FITs for ACRN and CRC in people aged 40-49 (younger age group) and ≥50 years (average risk group).
Ten studies with 664,159 FITs were included. The FIT positivity rate was 4.9% and 7.3% for the younger age and average risk groups, respectively. Younger individuals with positive FIT results had significantly higher risks of ACRN (odds ratio OR 2.58, 95% confidence interval CI 1.79-3.73) or CRC (OR 2.86, 95% CI 1.59-5.13) than did individuals in the average-risk group, regardless of FIT results. Individuals aged 45-49 years with positive FIT results had a similar risk of ACRN (OR 0.80, 95% CI 0.49-1.29) to that of people aged 50-59 years with positive FIT results, although significant heterogeneity was observed. The positive predictive values of the FIT were 10-28.1% for ACRN and 2.7-6.8% for CRC in the younger age group.
The detection rate of ACRN and CRC based on FITs in individuals aged 40-49 years is acceptable, and the yield of ACRN might be similar between individuals aged 45-49 and 50-59 years. Further prospective cohort and cost-effective analysis are warranted.
Cancer cells with mesenchymal attributes potentially display chemoresistance. Cancer stem cells (CSCs), which are intrinsically resistant to most chemotherapy agents, exhibit considerable phenotypic ...heterogeneity in their epithelial versus mesenchymal states. However, the drug response of CSCs in the epithelial and mesenchymal states has not been completely investigated. In this study, we found that epithelial-type (E-cadherin
/CD133
) CSCs displayed a higher sphere formation ability and chemoresistance than mesenchymal-type (E-cadherin
CD133
) CSCs. Gene expression profiling of the CSC and non-CSC subpopulations with distinct epithelial-to-mesenchymal transition (EMT) states showed that MyoD family inhibitor domain-containing (MDFIC) was selectively upregulated in epithelial-type CSCs. Knockdown of MDFIC sensitized epithelial-type CSCs to chemotherapy agents. Ectopic expression of MDFIC increased the chemoresistance of mesenchymal-type CSCs. In a tissue microarray, high MDFIC expression was associated with poor prognosis of non-small cell lung cancer (NSCLC) patients. A mechanistic study showed that the MDFIC p32 isoform, which is located in the cytoplasm, interacted with the destruction complex, Axin/GSK-3/β-catenin. This interaction stabilized β-catenin by inhibiting β-catenin phosphorylation at S33/37 and increased the nuclear translocation and transcriptional activity of β-catenin. Knockdown of β-catenin decreased MDFIC-enhanced chemoresistance. These results suggested that the upregulation of MDFIC enhanced the chemoresistance of epithelial-type CSCs by elevating β-catenin activity. Thus, targeting MDFIC-regulated β-catenin signaling of epithelial-type CSCs may be a potential strategy to overcome chemoresistance in NSCLC.
In this study, a method for the efficient production of dehydroepiandrosterone (DHEA) from phytosterols in a vegetable oil/aqueous two-phase system by
Mycobacterium
sp
.
was developed. After the ...3-hydroxyl group of phytosterols was protected, they could be converted into DHEA with high yield and productivity by
Mycobacterium
sp
.
NRRL B-3683. In a shake flask biotransformation, 15.05 g l
−1
of DHEA and a DHEA yield of 85.39% (mol mol
−1
) were attained after 7 days with an initial substrate concentration of 25 g l
−1
. When biotransformation was carried out in a 30-l stirred bioreactor with 25 g l
−1
substrate, the DHEA concentration and yield was 16.33 g l
−1
and 92.65% (mol mol
−1
) after 7 days, respectively. The results of this study suggest that inexpensive phytosterols could be utilized for the efficient production of DHEA.
The study of dynamic supramolecular chirality inversion (SMCI) not only helps to deepen the understanding of chiral transfer and amplification in both living organizations and artificially chemical ...self-assembly systems but also is useful for the development of smart chiral nanomaterials. However, it is still challenging to achieve the dynamic SMCI of the self-aggregation of metal–organic supramolecular polymers with great potential in asymmetric synthesis, chiroptical switches, and circular polarized luminescence. Here, we successfully developed a hierarchical coassembly system based on the mPAzPCC and various metal ions with effective chirality transfer and temporal-controlled SMCI. Due to the dynamic self-assembly and hierarchical chirality transfer of the Ag+/mPAzPCC complex driven by metallophilic interaction and coordination, morphological transition with nanoribbons, helical nanoribbons, and chiral nanotubules was successively obtained. Interestingly, the SMCI of chiral nanoaggregates was precisely regulated by solvents and metal ions in the Cu2+/mPAzPCC and Mn2+/mPAzPCC system. Besides, temporal-controlled dynamic SMCI switching from helix to bundled helix was clearly revealed in the aggregation of Cu2+/mPAzPCC, Mn2+/mPAzPCC, and Bi3+/mPAzPCC systems. This work provides a metallophilic interaction-mediated helical assembly pathway to dynamically modulate the chirality of metal–organic complex-based assemblies and deepen the understanding of the hierarchically dynamic self-assembly process, which would be of great potential in metal ion-mediated supramolecular asymmetric catalysis and bioinspired chiral sensing.
Background:
We aimed to study the safety of cold snare polypectomy (CSP) for colorectal polyps in patients administered periprocedural antithrombotic agents.
Methods:
We searched the PubMed, Embase, ...and Cochrane Library databases through June 2021. The primary outcomes were the rates of delayed and immediate bleeding (requiring endoscopic hemostasis). Secondary outcomes included thromboembolic events. Meta-analysis using odds ratios (ORs) and corresponding 95% confidence intervals (CIs) was performed to compare the outcomes.
Results:
Seventeen studies, including five randomized trials, were included. Over 96% of polyps were ⩽1 cm. The pooled rates of delayed and immediate bleeding for patients receiving CSP and periprocedural antithrombotic agents were 1.6% and 10.5%, respectively. Both the delayed (OR = 4.02, 95% CI = 1.98–8.17) and immediate bleeding (OR = 5.85, 95% CI = 3.84–8.89) rates were significantly higher in patients using periprocedural antithrombotic agents than in non-users. Although both antiplatelet agents and anticoagulants increased the risk of delayed bleeding, the risks associated with the use of direct oral anticoagulants (DOACs; 2.5%) or multiple agents (3.9%) were particularly high. Compared to their counterparts, diminutive polyps and uncomplicated lesions not requiring hemoclipping were associated with lower risks of delayed bleeding (pooled estimates of 0.4% and 0.18%, respectively). Thromboembolic risk was similar among patients using and not using periprocedural antithrombotic agents.
Conclusions:
CSP with periprocedural antiplatelet agents and warfarin may be feasible, especially for diminutive polyps. However, drug discontinuation should be considered with the use of DOACs or multiple agents which entail higher bleeding risk even with hemoclipping.
Lung cancer patients with human immunodeficiency virus (HIV) have a poorer prognosis than do patients without HIV infection. HIV1 Tat is a secreted viral protein that penetrates the plasma membrane ...and interacts with a number of proteins in non‐HIV‐infected cells. The loss of function of Tat‐interacting protein 30 (TIP30) has been linked to metastasis in non‐small cell lung cancer (NSCLC). However, it is unknown how the interaction of HIV1 Tat with TIP30 regulates the metastasis of NSCLC cells. In this study, the overexpression of TIP30 decreased tumor growth factor‐β‐induced epithelial‐to‐mesenchymal transition (EMT) and invasion of NSCLC cells, whereas the knockdown of TIP30 promoted EMT, invasion and stemness. Exposure to recombinant HIV1 Tat proteins promoted EMT and invasion. A mechanistic study showed that the interaction of HIV1 Tat with TIP30 blocked the binding of TIP30 to importin‐β, which is required for the nuclear translocation of Snail. Indeed, the loss of TIP30 promoted the nuclear translocation of Snail. In vivo studies demonstrated that the overexpression of TIP30 inhibited the metastasis of NSCLC cells. In contrast, the coexpression of HIV1 Tat and TIP30 diminished the inhibitory effect of TIP30 on metastasis. Immunohistochemistry confirmed that TIP30 overexpression reduced the nuclear localization of Snail, whereas the coexpression of HIV1 Tat and TIP30 increased nuclear Snail in metastatic tumors. In conclusion, the binding of HIV1 Tat to TIP30 enhanced EMT and metastasis by regulating the nuclear translocation of Snail. Targeting Tat‐interacting proteins may be a potential therapeutic strategy to prevent metastasis in NSCLC patients with HIV infection.
TIP30 competes with Snail for the binding to importin‐β and inhibits the nuclear translocation of Snail, which promotes EMT and invasion ability of cancer cells. Binding of HIV1 Tat to TIP30 blocks the interaction between TIP30 and importin‐β, leading to the increase of Snail nuclear translocation, invasion and distant metastasis of NSCLC cells.
A novel Fe-doped urchin-like Ni2P/Ni3S2 (NPZFNS@C/NF) heterostructure with abundant hetero-interfaces and carbon-coating is successfully constructed, which exhibits outstanding oxygen evolution ...reaction (OER) performance and excellent hydrogen evolution reaction (HER) performance. Furthermore, it also exhibits a small overpotential of 1.5 V for overall water splitting with NPZFNS/NF as both anode and cathode, lower than most of non-noble metal-based bifunctional electrocatalysts reported.
Display omitted
•Fe-doped Fe-Ni3S2/Ni2P@C/NF hetero-interface electrocatalyst is firstly constructed.•The catalyst shows oustanding OER and excellent HER performances.•It can act as a bifunctional catalyst toward excellent overall water splitting bebavior.•The unique electronic structure of the catalyst is the intrinsic reason for the excellent OER and HER performances.•DFT calculations further reveal the changes the d-band center and the rate-degerming step.
Interfacial engineering is an efficient strategy to develop electrocatalysts with excellent performance. By using this strategy, a novel Fe-doped urchin-like Ni2P/Ni3S2 (NPZFNS@C/NF) heterostructure with metal–organic frameworks (MOFs) as the precursor in-suit grows on nickel foam (NF) with abundant hetero-interfaces and carbon-coating is successfully constructed. Owing to the existence of hetero-interfaces and carbon coating, the unique surface electronic structure and d-band center of NPZFNS@C/NF are also obtained. Benefiting from the regulation of electronic structure and d-band center, the NPZFNS@C/NF electrode exhibits extremely high activity for oxygen evolution reaction (OER) and high activity for hydrogen evolution reaction (HER), which shows a very low overpotential of 141 mV at the current density of 10 mA cm−2 for OER and 129 mV for HER respectively in alkaline electrolyte. Furthermore, it also exhibits a small overpotential of 1.5 V for overall water splitting with NPZFNS@C/NF as both anode and cathode, which is lower than most of non-noble metal-based bifunctional electrocatalysts reported. Density functional theory (DFT) results further confirm that the hetero-interface with carbon coating can further optimize Gibbs free energies for both OER and HER processes. This design and constructure strategy provides a new avenue for overall water splitting.
Pigment epithelium-derived factor (PEDF) is a multifunctional protein that exhibits anti-angiogenic, antitumor, anti-inflammatory, antioxidative, anti-atherogenic, and cardioprotective properties. ...While it was recently shown that PEDF expression is inhibited under low oxygen conditions, the functional role of PEDF in response to hypoxia/reoxygenation (H/R) remains unclear. The goal of this study was to therefore investigate the influence of PEDF on myocardial H/R injury. For these analyses, PEDF-specific small interfering RNA-expressing and PEDF-expressing lentivirus (PEDF-LV) vectors were utilized to knockdown or stably overexpress PEDF, respectively, within human cardiomyocytes (HCM) in vitro. We noted that reactive oxygen species (ROS) play important roles in the induction of cell death pathways, including apoptosis and autophagy in ischemic hearts. Our findings demonstrate that overexpression of PEDF resulted in a significant reduction in ROS production and attenuation of mitochondrial membrane potential depletion under H/R conditions. Furthermore, PEDF inhibited the activation of a two-step apoptotic pathway in which caspase-dependent (caspase-9 and caspase-3) and caspase-independent (apoptosis inducing factor and endonuclease G), which in turn cleaves several crucial substrates including the DNA repair enzyme poly (ADP-ribose) polymerase. Meanwhile, overexpression of PEDF also promoted autophagy, a process that is typically activated in response to H/R. Therefore, these findings suggest that PEDF plays a critical role in preventing H/R injury by modulating anti-oxidant and anti-apoptotic factors and promoting autophagy.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Purpose. The present study investigated the risk factors for high myopia in adulthood, with a focus on the age at which children wore their first spectacles. Methods. Adults aged between 20 and 45 ...years were invited to complete a questionnaire about age, sex, current refractive error, high myopia in parents, early onset of myopia presented by the age of the first myopic spectacle prescription, refractive power of the first spectacles, and life habits at different educational stages. The associations between these factors and high myopia in adulthood were then evaluated and analyzed. Results. In total, 331 participants were enrolled. Their average refractive error was −4.03 diopters, and high myopia was noted in 27.5% of the study participants. Only 3.3% of participants had fathers with high myopia, while 6.0% had mothers with high myopia. The participants received their first myopic spectacle prescription at a mean age of 13.35 years, with a mean refractive error of −1.63 diopters. The significant risk factors for developing high myopia in adult life were earlier age of the first spectacles prescribed (p<0.001), higher refractive power of the first spectacles (p<0.001), mother with high myopia (p=0.015), and after-school class attendance in senior high school (p=0.018). Those who wore their first spectacles at <9 years of age were more predisposed to high myopia than those who did so at ≧13 years, with an odds ratio of 24.9. Conclusion. The present study shows that earlier onset of myopia, which is presented by the age of the first myopic spectacle prescription, higher myopic refraction of the first spectacles, mothers with high myopia, and after-school class attendance in senior high school are risk factors for high myopia in adulthood. It suggests that delaying the onset of myopia in children is important for the prevention of high myopia in later life.
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