Chrysophanol (CHR), a purified active constituent extracted from Rheum palmatum L., possesses anti‐inflammatory activity. This study aimed to evaluate its effects on asthma‐associated airway ...inflammation and remodeling. BALB/c mice were sensitized and challenged by ovalbumin (OVA) and administrated with different doses of CHR. We found that CHR decreased OVA‐induced pulmonary inflammation: the levels of interleukin (IL)‐4, IL‐5, and IL‐13, tumor necrosis factor (TNF)‐α, and inducible nitric oxide synthase were downregulated. CHR also attenuated airway remodeling induced by OVA challenge—CHR inhibited pulmonary α‐smooth muscle actin expression. Moreover, both the nuclear translocation and activity of NF‐κB p65 were inhibited by CHR in the asthmatic lung. Enhanced autophagy was initiated in the lung by OVA challenge as evidenced by upregulated light chain 3 beta, autophagy‐related protein 5, and Beclin 1. CHR suppressed OVA‐induced alterations in these autophagy‐related molecules. In vitro, CHR (2 or 20 μM) was used to treat human pulmonary epithelial BEAS‐2B cells in the presence of 10 ng/ml recombinant TNF‐α. CHR not only exhibited the antiproliferation effect but also inhibited the activation of nuclear factor‐kappa B (NF‐kB) signaling pathway in TNF‐α‐treated BEAS‐2B cells. In conclusion, our study indicates that CHR has the potential to ameliorate asthma.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Noninvasive prenatal testing (NIPT) for monogenic diseases by use of PCR-based strategies requires precise quantification of mutant fetal alleles circulating in the maternal plasma. The study ...describes the development and validation of a novel assay termed circulating single-molecule amplification and resequencing technology (cSMART) for counting single allelic molecules in plasma. Here we demonstrate the suitability of cSMART for NIPT, with Wilson Disease (WD) as proof of concept.
We used Sanger and whole-exome sequencing to identify familial ATP7B (ATPase, Cu(++) transporting, β polypeptide) gene mutations. For cSMART, single molecules were tagged with unique barcodes and circularized, and alleles were targeted and replicated by inverse PCR. The unique single allelic molecules were identified by sequencing and counted, and the percentage of mutant alleles in the original maternal plasma sample was used to determine fetal genotypes.
Four families with WD pedigrees consented to the study. Using Sanger and whole-exome sequencing, we mapped the pathogenic ATP7B mutations in each pedigree and confirmed the proband's original diagnosis of WD. After validation of cSMART with defined plasma models mimicking fetal inheritance of paternal, maternal, or both parental mutant alleles, we retrospectively showed in second pregnancies that the fetal genotypes assigned by invasive testing and NIPT were concordant.
We developed a reliable and accurate NIPT assay that correctly diagnosed the fetal genotypes in 4 pregnancies at risk for WD. This novel technology has potential as a universal strategy for NIPT of other monogenic disorders, since it requires only knowledge of the parental pathogenic mutations.
Abstract
Background
Worldwide, frozen embryo transfer (FET) has become a new strategy for the treatment of infertility. The success of FET is closely related to endometrial receptivity. Does uterine ...artery Doppler during the implantation window predict pregnancy outcome from the first FET?
Methods
A total of 115 retrospectively collected cycles were included in the study, with 64 cycles of clinical pregnancy and 51 cycles of nonclinical pregnancy; There were 99 nonabsent end-diastolic flow (NAEDF) cycles and 16 absent end-diastolic flow (AEDF) cycles. The differences in uterine artery Doppler findings between different pregnancy outcomes were investigated. The clinical pregnancy rate and spontaneous abortion rate in the NAEDF and AEDF groups were compared. The predictive value of uterine artery Doppler during the implantation window in the success rate of pregnancy from the first FET was also investigated.
Results
Between the clinical pregnancy group and the nonclinical pregnancy group, there were no significant differences in the mean resistance index (mRI) (Z = -1.065,
p
= 0.287), mean pulsatility index (mPI) (Z = -0.340,
p
= 0.734), and mean peak systolic/end-diastolic velocity(mS/D) (Z = -0.953,
p
= 0.341); there were significant differences in the mean peak systolic velocity (mPSV) (Z = -1.982,
p
= 0.048) and mean end-diastolic velocity (mEDV) (Z = -2.767,
p
= 0.006). Between the NAEDF and AEDF groups, there was no significant difference in the clinical pregnancy rate (χ2 = 0.003,
p
= 0.959), and there was a significant difference in the spontaneous abortion rate (χ2 = 3.465,
p
= 0.019). Compared with uterine artery Doppler alone, its combination with artificial abortion history, waist-to-hip ratio, LH (Luteinizing hormone) of P (Progesterone) administration day, mPSV and mEDV had a higher predictive value regarding clinical pregnancy from the first FET ROC-AUC 0.782, 95% CI (0.680–0.883) vs. 0.692, 95% CI (0.587–0.797).
Conclusions
Uterine artery Doppler, particularly mPSV and mEDV during the implantation window, was useful for predicting clinical pregnancy, and AEDF was related to spontaneous abortion in the first trimester. Uterine artery Doppler combined with artificial abortion history, waist-to-hip ratio, LH of P administration day, mPSV and mEDV have a higher predictive value than uterine artery Doppler alone regarding the pregnancy from the first FET.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Echinococcosis is a chronic zoonosis caused by tapeworms of the genus Echinococcus. Treatment of the disease is often expensive and complicated, sometimes requiring extensive surgery. ...Ultrasonographic imaging is currently the main technique for diagnosis, while immunological analysis provides additional information. Confirmation still needs pathological analysis. However, these diagnostic techniques generally detect infection in late stages of the disease. An accurate, early and non-invasive molecular diagnostic method is still unavailable.
We sequenced the cell-free DNA (cfDNA) from plasma of echinococcosis patients and confirmed the presence of Echinococcus DNA. To improve detection sensitivity, we developed a method based on targeted next-generation sequencing of repeat regions. Simulation experiments demonstrate that the targeted sequencing is sensitive enough to detect as little as 0.1% of an Echinococcus genome in 1 mL of plasma. Results obtained using patient plasma shows that the Area Under the Curve (AUC) of the method is 0.862, with a detection sensitivity of 62.50% and specificity of 100%, corresponding to a Youden-index of 0.625.
This study provides evidence that hydatid cysts release cfDNA fragments into patient plasma. Using the repeat region targeted sequencing method, highly specific detection of Echinococcus infection was achieved. This study paves a new avenue for potential non-invasive screening and diagnosis of echinococcosis.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Noninvasive prenatal testing (NIPT) for monogenic disorders has been developed in recent years; however, there are still significant technical and analytical challenges for clinical use. The clinical ...feasibility of NIPT for methylmalonic acidemia cblC type (cblC type MMA) was investigated using our circulating single-molecule amplification and re-sequencing technology (cSMART). Trios molecular diagnosis was performed in 29 cblC type MMA-affected children and their parents by traditional Sanger sequencing. In the second pregnancy, invasive prenatal diagnosis (IPD) of the pathogenic
gene was used to determine fetal genotypes, and NIPT was performed using a novel
gene-specific cSMART assay. Maternal-fetal genotypes were deduced based on the mutation ratio in maternal plasma DNA. Concordance of fetal genotypes between IPD and NIPT, and the sensitivity and specificity of NIPT were determined. After removing two cases with a low
value or reads, the concordance ratio for NIPT and IPD was 100.00% (27/27), and the sensitivity and specificity were 100.00% (54.07-100.00%) and 100.00% (83.89-100.00%), respectively. This study demonstrates that NIPT using the cSMART assay for cblC type MMA was accurate in detecting fetal genotypes. cSMART has a potential clinical application as a prenatal diagnosis and screening tool for carrier and low-risk genotypes of cblC type MMA and other monogenic diseases.
3-hydroxyisobutryl-CoA hydrolase (HIBCH) deficiency is a rare inborn error of valine metabolism characterized by neurodegenerative symptoms and caused by recessive mutations in the HIBCH gene. In ...this study, utilizing whole exome sequencing, we identified two novel splicing mutations of HIBCH (c.304+3A>G; c.1010_1011+3delTGGTA) in a Chinese patient with characterized neurodegenerative features of HIBCH deficiency and bilateral syndactyly which was not reported in previous studies. Functional tests showed that both of these two mutations destroyed the normal splicing and reduced the expression of HIBCH protein. Through a literature review, a potential phenotype-genotype correlation was found that patients carrying truncating mutations tended to have more severe phenotypes compared with those with missense mutations. Our findings would widen the mutation spectrum of HIBCH causing HIBCH deficiency and the phenotypic spectrum of the disease. The potential genotype-phenotype correlation would be profitable for the treatment and management of patients with HIBCH deficiency.
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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
Reconfigurable Intelligent Surface (RIS) is one of the promising techniques for 6G wireless communications, and recently has also been shown to be able to improve secure communications. However, ...there is a "double fading" effect in the reflection link between base station and user, thus passive RIS only achieves a negligible secrecy gain in typical communications scenarios. In this letter, we propose an active RIS-aided multi-antenna physical layer secrecy transmission scheme, where the active RIS can amplify the signal actively. Our aim is to minimize the transmit power subject to the constraint of secrecy rate. To solve the non-convex optimization problem, a penalty-based alternating minimization (AltMin) algorithm is proposed to optimize both the beamformer at the transmitter and the reflection matrix at RIS. Simulation results show that active RIS can resist the impact of "double fading" effect effectively, and is more energy efficient than passive RIS.
This study summarized the available randomized controlled trials (RCTs) to assess the efficacy and safety of macrolides on pathogens, lung function, laboratory parameters, and safety in children with ...bronchiectasis.
PubMed, EMBASE, and the Cochrane Library were searched for available papers published up to June 2021. The outcomes were the pathogens, adverse events (AEs), and the forced expiratory volume in one second (FEV1%) predicted.
Seven RCTs (633 participants) were included. The long-term use of macrolides reduced the risk of the presence of Moraxella catarrhalis (RR = 0.67, 95% CI: 0.30-1.50, P = 0.001; I
= 0.0%, P
= 0.433), but not Haemophilus influenza (RR = 0.19, 95% CI: 0.08-0.49, P = 0.333; I
= 57.0%, P
= 0.040), Streptococcus pneumonia (RR = 0.91, 95% CI: 0.61-1.35, P = 0.635; I
= 0.0%, P
= 0.515), Staphylococcus aureus (RR = 1.01, 95% CI: 0.36-2.84, P = 0.986; I
= 61.9%, P
= 0.033), and any pathogens present (RR = 0.61, 95% CI: 0.29-1.29, P = 0.195; I
= 80.3%, P
= 0.006). Long-term macrolides had no effect on FEV1% predicted (WMD = 2.61, 95% CI: -1.31, 6.53, P = 0.192; I
= 0.0%, P
= 0.896). Long-term macrolides did not increase the risk of AEs or serious AEs.
Macrolides do not significantly reduce the risk of pathogens present (except for Moraxella catarrhalis) or increase FEV1% predicted among children with bronchiectasis. Moreover, macrolides were not associated with AEs. Considering the limitations of the meta-analysis, further larger-scale RCTs are needed to confirm the findings.
Macrolides do not significantly reduce the risk of pathogens present (except for Moraxella catarrhalis) among children with bronchiectasis. Macrolides do not significantly increase FEV1% predicted among children with bronchiectasis. This meta-analysis reports on the efficacy and safety of macrolides in the treatment of children with bronchiectasis, providing evidence for the management of children with bronchiectasis. This meta-analysis does not support the use of macrolides in the management of children with bronchiectasis unless the presence of Moraxella catarrhalis is provenor suspected.
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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
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