Aim
A prenatal diagnosis of coarctation of the aorta (CoA) is challenging. This study aimed to develop a coarctation probability model incorporating prenatal cardiac sonographic markers to estimate ...the probability of an antenatal diagnosis of CoA.
Methods
We reviewed 89 fetuses as an investigation cohort with prenatal suspicion for CoA and categorized them into three subgroups: severe CoA: symptomatic CoA and surgery within the first 3 months; mild CoA: surgery within 4 months to 1 year (29); and false‐positive CoA: not requiring surgery (45). Logistic regression was used to create a multiparametric model, and a validation cohort of 86 fetuses with suspected CoA was used to validate the model.
Results
The prediction model had an optimal criterion >0.25 (sensitivity of 97.7%; specificity of 59.1%), and the area under the receiver operator curve was 0.85. The parameters and their cut‐off values were as follows: left common carotid artery to left subclavian artery distance/distal transverse arch (LCCA‐LSCA)/DT Index >1.77 (sensitivity 62%, specificity 88%, 95% confidence interval CI: 0.6–0.8), and z‐score of AAo peak Doppler > −1.7 (sensitivity 77%, specificity 56%, 95% CI: 0.6–0.8). The risk assessment demonstrated that fetuses with a model probability >60% should have inpatient observation for a high risk of CoA, whereas fetuses with a model probability <15% should not undergo clinical follow‐up.
Conclusion
The probability model performs well in predicting CoA outcomes postnatally and can also improve the accuracy of risk assessment. The objectivity of its parameters may allow its implementation in multicenter studies of fetal cardiology.
Human infections with zoonotic coronaviruses (CoVs), including severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV, have raised great public health concern ...globally. Here, we report a novel bat-origin CoV causing severe and fatal pneumonia in humans.
We collected clinical data and bronchoalveolar lavage (BAL) specimens from five patients with severe pneumonia from Wuhan Jinyintan Hospital, Hubei province, China. Nucleic acids of the BAL were extracted and subjected to next-generation sequencing. Virus isolation was carried out, and maximum-likelihood phylogenetic trees were constructed.
Five patients hospitalized from December 18 to December 29, 2019 presented with fever, cough, and dyspnea accompanied by complications of acute respiratory distress syndrome. Chest radiography revealed diffuse opacities and consolidation. One of these patients died. Sequence results revealed the presence of a previously unknown β-CoV strain in all five patients, with 99.8% to 99.9% nucleotide identities among the isolates. These isolates showed 79.0% nucleotide identity with the sequence of SARS-CoV (GenBank NC_004718) and 51.8% identity with the sequence of MERS-CoV (GenBank NC_019843). The virus is phylogenetically closest to a bat SARS-like CoV (SL-ZC45, GenBank MG772933) with 87.6% to 87.7% nucleotide identity, but is in a separate clade. Moreover, these viruses have a single intact open reading frame gene 8, as a further indicator of bat-origin CoVs. However, the amino acid sequence of the tentative receptor-binding domain resembles that of SARS-CoV, indicating that these viruses might use the same receptor.
A novel bat-borne CoV was identified that is associated with severe and fatal respiratory disease in humans.
Asymmetric hydroxycarbonylation is one of the most fundamental yet challenging methods for the synthesis of carboxylic acids. Herein, we reported the development of a palladium‐catalyzed highly ...enantioselective Markovnikov hydroxycarbonylation of vinyl arenes with CO and water. A monodentate phosphoramidite ligand L6 plays vital role in the reaction. The reaction tolerates a range of functional groups, and provides a facile and atom‐economical approach to an array of 2‐arylpropanoic acids including several commonly used non‐steroidal anti‐inflammatory drugs. The catalytic system has also enabled an asymmetric Markovnikov hydroalkoxycarbonylation of vinyl arenes with alcohols to afford 2‐arylpropanates. Mechanistic investigations suggested that the hydropalladation is irreversible and is the regio‐ and enantiodetermining step, while hydrolysis/alcoholysis is probably the rate‐limiting step.
A Pd‐catalyzed highly enantioselective Markovnikov hydroxycarbonylation of vinyl arenes with CO and water for the synthesis of 2‐arylpropanoic acids has been developed. Several non‐steroidal anti‐inflammatory drugs including ibuprofen, naproxen, flurbiprofen, fenoprofen, and ketoprofen were synthesized in high yields and ees in gram scale.
Streptococcus pneumoniae (S. pneumoniae) is a major cause of bacterial meningitis, septicemia and pneumonia in children. Inappropriate choice of antibiotic can have important adverse consequences for ...both the individual and the community. Here, we focused on penicillin/cefotaxime non-susceptibility of S. pneumoniae and evaluated appropriateness of targeted antibiotic therapy for children with IPD (invasive pneumococcal diseases) in China. A multicenter retrospective study was conducted in 14 hospitals from 13 provinces in China. Antibiotics prescription, clinical features and resistance patterns of IPD cases from January 2012 to December 2017 were collected. Appropriateness of targeted antibiotics therapy was assessed. 806 IPD cases were collected. The non-susceptibility rates of S. pneumoniae to penicillin and cefotaxime were 40.9% and 20.7% respectively in 492 non-meningitis cases, whereas those were 73.2% and 43.0% respectively in 314 meningitis cases. Carbapenems were used in 21.3% of non-meningitis cases and 42.0% of meningitis cases for targeted therapy. For 390 non-meningitis cases with isolates susceptible to cefotaxime, vancomycin and linezolid were used in 17.9% and 8.7% of cases respectively for targeted therapy. For 179 meningitis cases with isolates susceptible to cefotaxime, vancomycin and linezolid were prescribed in 55.3% and 15.6% of cases respectively. Overall, inappropriate targeted therapies were identified in 361 (44.8%) of 806 IPD cases, including 232 (28.8%) cases with inappropriate use of carbapenems, 169 (21.0%) cases with inappropriate use of vancomycin and 62 (7.7%) cases with inappropriate use of linezolid. Antibiotic regimens for IPD definite therapy were often excessive with extensive prescription of carbapenems, vancomycin or linezolid in China. Antimicrobial stewardship programs should be implemented to improve antimicrobial use.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
There is an urgent need for vaccines against coronavirus disease 2019 (COVID-19) because of the ongoing SARS-CoV-2 pandemic. Among all approaches, a messenger RNA (mRNA)-based vaccine has emerged as ...a rapid and versatile platform to quickly respond to this challenge. Here, we developed a lipid nanoparticle-encapsulated mRNA (mRNA-LNP) encoding the receptor binding domain (RBD) of SARS-CoV-2 as a vaccine candidate (called ARCoV). Intramuscular immunization of ARCoV mRNA-LNP elicited robust neutralizing antibodies against SARS-CoV-2 as well as a Th1-biased cellular response in mice and non-human primates. Two doses of ARCoV immunization in mice conferred complete protection against the challenge of a SARS-CoV-2 mouse-adapted strain. Additionally, ARCoV is manufactured as a liquid formulation and can be stored at room temperature for at least 1 week. ARCoV is currently being evaluated in phase 1 clinical trials.
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•Development of LNP-encapsulated mRNA vaccine (ARCoV) targeting the RBD of SARS-CoV-2•ARCoV induces neutralizing antibodies and T cell immunity in mice and NHPs•ARCoV vaccination confers full protection against SARS-CoV-2 challenge in mice•ARCoV is a thermostable vaccine candidate for phase I studies
ARCoV is an LNP-encapsulated mRNA vaccine platform that is highly immunogenic and safe in mice and non-human primates, conferring protection against challenge with a SARS-CoV-2 mouse-adapted strain.
Esophageal squamous cell carcinoma (ESCC) has the highest mortality rates in China. The 5-year survival rate of ESCC remains dismal despite improvements in treatments such as surgical resection and ...adjuvant chemoradiation, and current clinical staging approaches are limited in their ability to effectively stratify patients for treatment options. The aim of the present study, therefore, was to develop an immunohistochemistry-based prognostic model to improve clinical risk assessment for patients with ESCC.
We developed a molecular prognostic model based on the combined expression of axis of epidermal growth factor receptor (EGFR), phosphorylated Specificity protein 1 (p-Sp1), and Fascin proteins. The presence of this prognostic model and associated clinical outcomes were analyzed for 130 formalin-fixed, paraffin-embedded esophageal curative resection specimens (generation dataset) and validated using an independent cohort of 185 specimens (validation dataset).
The expression of these three genes at the protein level was used to build a molecular prognostic model that was highly predictive of ESCC survival in both generation and validation datasets (P = 0.001). Regression analysis showed that this molecular prognostic model was strongly and independently predictive of overall survival (hazard ratio = 2.358 95% CI, 1.391-3.996, P = 0.001 in generation dataset; hazard ratio = 1.990 95% CI, 1.256-3.154, P = 0.003 in validation dataset). Furthermore, the predictive ability of these 3 biomarkers in combination was more robust than that of each individual biomarker.
This technically simple immunohistochemistry-based molecular model accurately predicts ESCC patient survival and thus could serve as a complement to current clinical risk stratification approaches.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Late Carboniferous–middle Permian magmatism in the Jiamusi Massif of northeast China, in the eastern segment of the Central Asian Orogenic Belt (CAOB), provides critical evidence regarding the ...tectonic history and geodynamic processes in the region. The gabbro–diorites of the Longtouqiao pluton and two groups of coeval granite in the study area comprise a bimodal magmatic suite. Precise LA-ICP-MS U–Pb zircon ages indicate that the granitoids and gabbro–diorites were emplaced in the late Carboniferous–middle Permian (302–267Ma). Group I granites have high SiO2 (70.75–77.04wt.%) and K2O (3.65–5.89wt.%) contents, are enriched in LILEs (e.g., Rb, Th, and U) relative to HFSEs and LREEs, and have negative Nb, Ta, P, and Ti anomalies, which collectively indicate affinities with subduction-related magmas. Group II granites are weakly peraluminous (A/CNK=1.03–1.07) and are characterized by enrichment in alkalis (Na2O+K2O=8.22–8.90wt.%), low MgO (0.04–0.09wt.%) and P2O5 (0.01–0.04wt.%) contents, high Zr and Nb contents, high 10,000×Ga/Al ratios, and they are geochemically similar to aluminous A-type granites. All the magmatic zircons in these granitoids have great variations of εHf(t) (+7.89 to −5.60) and two-stage Hf model ages (TDM2) of 0.8–1.7Ga, which suggest that the precursor magmas originated from a heterogeneous source that involved juvenile components derived from a depleted mantle source during magma generation. The aluminous A-type granite magmas were probably derived by high-temperature partial melting of a felsic crustal source, whereas the other granite magmas probably resulted from partial melting of a mafic lower crust. The gabbro–diorites of the Longtouqiao pluton are depleted in Nb, Ta, P, and Ti, and show flat distributions of most LILEs and HFSEs, except for large positive anomalies in Ba, K, and Pb. These features reflect a limited degree of crustal contamination associated with the subduction-related magmatic processes. These data, together with previously reported data and the nature of various rock types along the eastern part of the Jiamusi Massif, suggest that the intrusive rocks were formed in a geodynamic regime that changed from compression to extension during the westwards subduction of the Paleo-Pacific oceanic lithosphere, probably as a result of slab break-off of the subducting plate.
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•The studied intrusions in the Jiamusi Massif were emplaced at 302–267Ma.•The I- and A-type granites formed by different crustal contributions.•The gabbro–diorites were derived from heterogeneous mantle sources.•A slab break-off probably existed during the Permian.
Core Ideas
SCN3‐11 (closest paralog of rhg1‐b) explained 5.8% phenotypic variance for SCN resistance
The combination of rhg1‐b and SCN3‐11 provides a high level of SCN resistance
Joint LM‐AM approach ...can aid in revealing the genetic basis of a complex trait
A set of 585 informative single‐nucleotide polymorphism (SNP) loci was used to genotype both a panel of diverse accessions and a set of recombinant inbred lines (RILs) bred from the cross Zhongpin03‐5373 (ZP; resistant to SCN) × Zhonghuang13 (ZH; susceptible). The SNP loci are mostly sited within genic sequence in regions of the soybean Glycine max (L.) Merr. genome thought to harbor genes determining resistance to the soybean cyst nematode (SCN, Heterodera glycines Ichinohe). The three strongest quantitative trait nucleotides (QTNs) identified by association mapping (AM) involved the genes Glyma18 g02590 (a component of the multigene locus rhg1‐b), Glyma11 g35820 and Glyma11 g35810 (an rhg1‐b paralog), as well as some other loci with smaller effects. The linkage mapping (LM) analysis performed using the RILs revealed two putative quantitative trait loci (QTL): one mapping to rhg1‐b and the other to an rhg1‐b paralog; both of these loci were also identified by AM. The former locus explained 25.5% of the phenotypic variance for SCN resistance and the latter 5.8%. In combination, the two major loci acted nonadditively, providing a high level of SCN resistance.
A recurrence of hepatocellular carcinoma (HCC) after living donor liver transplantation (LDLT) is one of the major concerns reflecting the higher mortality of HCC. This study aimed to explore the ...impact of circulating exosomes on HCC development and recurrence. One‐shot transfusion of hepatoma serum to naïve rats induced liver cancer development with gradual elevation of alpha‐fetoprotein (AFP), but exosome‐free hepatoma serum failed to induce AFP elevation. The microarray analysis revealed miR‐92b as one of the highly expressing microribonucleic acids in hepatoma serum exosomes. Overexpression of miR‐92b enhanced the migration ability of liver cancer cell lines with active release of exosomal miR‐92b. The hepatoma‐derived exosomal miR‐92b transferred to natural killer (NK) cells, resulting in the downregulation of CD69 and NK cell‐mediated cytotoxicity. Furthermore, higher expression of miR‐92b in serum exosomes was confirmed in HCC patients before LDLT, and its value at 1 month after LDLT was maintained at a higher level in the patients with posttransplant HCC recurrence. In summary, we demonstrated the impact of circulating exosomes on liver cancer development, partly through the suppression of CD69 on NK cells by hepatoma‐derived exosomal miR‐92b. The value of circulating exosomal miR‐92b may predict the risk of posttransplant HCC recurrence.
This study demonstrates the impact of circulating exosomes on liver cancer development in rats, explores functional roles of exosomal miR‐92b in the tumor microenvironment, and verifies its clinical value for early prediction of posttransplant hepatocellular carcinoma recurrence.
As a rapidly growing family of 2D transition metal carbides and nitrides, MXenes are recognized as promising materials for the development of future electronics and optoelectronics. So far, the ...reported patterning methods for MXene films lack efficiency, resolution, and compatibility, resulting in limited device integration and performance. Here, a high‐performance MXene image sensor array fabricated by a wafer‐scale combination patterning method of an MXene film is reported. This method combines MXene centrifugation, spin‐coating, photolithography, and dry‐etching and is highly compatible with mainstream semiconductor processing, with a resolution up to 2 µm, which is at least 100 times higher than other large‐area patterning methods reported previously. As a result, a high‐density integrated array of 1024‐pixel Ti3C2Tx/Si photodetectors with a detectivity of 7.73 × 1014 Jones and a light–dark current ratio (Ilight/Idark) of 6.22 × 106, which is the ultrahigh value among all reported MXene‐based photodetectors, is fabricated. This patterning technique paves a way for large‐scale high‐performance MXetronics compatible with mainstream semiconductor processes.
MXenes are promising for future electronics and optoelectronics; however, previously reported patterning methods lack efficiency, resolution, and compatibility with mainstream semiconductor processing. Here, a wafer‐scale combination patterning method with a resolution up to the micrometer scale is developed, resulting in an integrated array of 1024‐pixel Ti3C2Tx/Si photodetectors with a record‐high detectivity of 7.73 × 1014 Jones.
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