Introduction
The α‐globin fusion gene between the HBA2 and HBAP1 genes becomes clinically important in thalassemia screening because this fusion gene can cause severe hemoglobin (Hb) H disease when ...combining with α0‐thalassemia (α0‐thal). Due to its uncommon rearrangement in the α gene cluster without dosage changes, this fusion gene is undetectable by common molecular testing approaches used for α‐thal diagnosis.
Methods
In this study, we used the single‐molecule real‐time (SMRT) sequencing technique to detect this fusion gene in 23 carriers identified by next‐generation sequencing (NGS) among 16,504 screened individuals. Five primers for α and β thalassemia were utilized.
Results
According to the NGS results, the 23 carriers include 14 pure heterozygotes, eight compound heterozygotes with common α‐thal alleles, and one homozygote. By using SMRT, the fusion mutant was successfully detected in all 23 carriers. Furthermore, SMRT corrected the diagnosis in two “pure” heterozygotes: one was compound heterozygote with anti‐3.7 triplication, and the other was homozygote.
Conclusion
Our results indicate that SMRT is a superior method compared to NGS in detecting the α fusion gene, attributing to its efficient, accurate, and one‐step properties.
Concurrent chemoradiotherapy (CRT) is the preferred treatment strategy for inoperable esophageal cancer (EC). However, the effect of CRT needs to be improved.
This study comprehensively analyzed ...targeted agents combined with CRT for the treatment of EC by a network meta-analysis. The search was performed in public databases from incipient to 5 August 2021. Randomized controlled trials comparing the effect of targeted agents combined with CRT and CRT alone on EC patients were included.
Ten studies were included. For progression-free survival (PFS), nivolumab (67.4%) and erlotinib (64.6%) had advantages based on Cox analysis. Regarding the frequency of PFS, cetuximab (OR: 1.39; 95% CI: 1.01, 1.91; p=0.042) and nivolumab (OR: 1.81; 95% CI: 1.34, 2.44; p<0.01) were significantly superior to the control. For overall survival (OS), nivolumab (71.6%) in Cox analysis and nimotuzumab (69.7%) in frequency analysis were found to have relative advantages. Nimotuzumab combined with CRT was significantly better than the control with regard to endoscopic and the pathologic complete response (epCR; OR: 2.81; 95% CI: 1.28, 6.14; p=0.011) and objective response rate (ORR; 4.71; 95% CI: 1.45, 15.29; p=0.008). The targeted drugs were not associated with significant SEA risk.
In conclusion, compared to CRT alone, cetuximab and nivolumab combined with CRT were found to significantly improve the PFS rate only based on the frequency results. However, there was no benefit in terms of OS. For epCR and ORR, nimotuzumab was better than the blank control. Considering the limitations in this study, more well-designed RCTs are needed in the future to validate the results.
For filamentous fungi, conidiogenesis is the most common reproductive strategy for environmental dispersal, invasion, and proliferation. Understanding the molecular mechanisms controlling conidiation ...and increasing conidium yield may provide promising applications in commercial development in the future for nematode-trapping fungi. However, the molecular mechanism for regulating conidium production of filamentous fungi is not fully understood. In this study, we characterized three novel conidiogenesis-related genes via gene knockout in A. oligospora. The absence of the genes AoCorA and AoRgsD caused significant increases in conidia production, while the absence of AoXlnR resulted in a decrease in conidiogenesis. Moreover, we characterized the ortholog of AbaA, a well-known conidiogenesis-related gene in Aspergillus nidulans. The deletion of AoAbaA not only completely abolished conidium production but also affected the production of nematode-trapping traps.
Rosmarinic acid (RA), an ester compound of caffeic acid (CA) and 3,4‐dihydroxyphenyllacic acid, is widely distributed in the herbs of the Lamiaceae family and has shown a wide spectrum of ...pharmacological properties. CA and FA (ferulic acid) are two bioactive metabolites in vivo after oral administration of RA; however, a rapid and robust analytical approach that can enable the quantitative assay of RA and two bioactive metabolites is still lacking. A liquid chromatography/tandem mass spectrometry method was established that was capable of the quantitative determination of RA, CA and FA by negative‐mode multiple reaction monitoring within 7 min using a Zorbax SB‐C18 column and an isocratic elution. This assay method was validated as linear over the investigated ranges with correlation coefficients (r) > 0.9950. The intra‐ and inter‐day precision was <10.65%, and the accuracies (relative error, %) <−6.41%. The validated approach was applied to a pharmacokinetics study of RA and its two metabolites in rats after oral and intravenous administration. RA was rapidly metabolized in both administration modes, whilst the metabolites CA and FA were only detectable by oral administration. The absolute availability of RA was calculated to be 4.13%.
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