Missing microbes in infants and children in the COVID-19 pandemic: a study of 1,126 participants in Beijing, China.

The COVID-19 pandemic has caused many fatalities worldwide and continues to affect the health of the recovered patients in the form of long-COVID. In this study, we compared the gut microbiome of uninfected infants and children before the pandemic began (BEFORE cohort, n=906) to that of after the pandemic (AFTER cohort, n=220) to examine the potential impact of social distancing and life habit changes on infant/children gut microbiome. Based on 16S rRNA sequencing, we found a significant change in microbiome composition after the pandemic, with Bacteroides enterotype increasing to 35.45% from 30.46% before the pandemic. qPCR quantification indicated that the bacterial loads of seven keystone taxa decreased by 91.69%-19.58%. Quantitative microbiome profiling, used to enhance the resolution in detecting microbiome differences, revealed a greater explained variance of pandemic on microbiome compared to gender, as well as a significant decrease in bacterial loads in 15 of the 20 major genera. The random forest age-predictor indicated the gut microbiomes were less mature in the after-pandemic cohort than in the before-pandemic cohort in the children group (3-12 years old) and had features of a significantly younger age (average of 1.86 years). Lastly, body weight and height were significantly lower in the after-pandemic cohort than in the before-pandemic cohort in infants (<1 year of age), which was associated with a decrease in bacterial loads in the fecal microbiome.

Response of human epidermal growth factor receptor 2-positive colorectal cancer to lapatinib monotherapy: A case report.

BACKGROUND: Human epidermal growth factor receptor 2 (HER2) amplification is a molecular driver for a subset of colorectal cancers (CRCs) and one of the major causes of anti-epidermal growth factor receptor (EGFR) treatment failure. Compared to dual anti-HER2 treatments, which have been shown to be effective in HER2-positive metastatic CRC patients, single-agent anti-HER2 therapy is rarely used to treat CRC. CASE SUMMARY: Herein, we report a case of RAS/BRAF-wild-type metastatic CRC that was identified as HER2-positive through circulating tumor DNA (ctDNA) testing by next-generation sequencing following the failure of two lines of therapy. Subsequently, the patient was given lapatinib monotherapy that led to a partial response with a progression-free survival of 7.9 mo. Moreover, serial ctDNA detection was used to monitor the efficacy of lapatinib. The aberration of HER2 copy number disappeared when radiographic assessment revealed a partial response. However, a high level of HER2 amplification was detected again at the time of disease progression. Finally, a phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha mutation was identified at the time of tumor progression, which may explain the acquired resistance to lapatinib. CONCLUSION: This is the first case report of HER2-positive RAS/BRAF wild-type metastatic CRC patient responding to lapatinib monotherapy. It highlights that ctDNA testing is an effective and feasible approach to evaluate the efficacy of anti-HER2 therapy.

Variations in early gut microbiome are associated with childhood eczema.

We assessed the relationship between gut microbiome profile and childhood eczema in 172 subjects (age < 3 years, healthy group N = 123, eczema group N = 49) utilizing 16S rRNA gene sequencing. Lower relative abundance of Bifidobacterium was shown to be associated with childhood eczema. Considering that developmental and environmental factors could modify the state of children's gut microbiome, we divided the samples into four age groups: 0-0.5 years, 0.5-1 years, 1-2 years and 2-3 years for farther analyses. Data revealed significant inter-group differences between healthy and eczema samples in all age groups, and decreased microbial diversity was most significantly found in children with eczema of age 2-3 years old. Decreased abundance of Bifidobacterium was a major finding in eczema groups from 0.5-3 years compared to the age matched healthy controls, but not significant in children younger than 6 month old. Of note, Bifidobacterium operational taxonomic units were identified by Random Forest with highly predictive power of 0.83 (AUC = 0.83) in ROC analysis, which also confirmed its role as a key genus that is associated with eczema. To verify the sequencing results, we performed quantitative polymerase chain reaction of Bifidobacterium and Bacteroides in the same cohort, and in a new eczema cohort (N = 57) for validation. Significantly, lower Bifidobacterium quantities were found in both eczema groups with an age range of 0.5-3 years. These results suggest variations in early gut microbiome are associated with childhood eczema.

Identification and functional analysis of long non-coding RNAs in mouse cleavage stage embryonic development based on single cell transcriptome data.

BACKGROUND: Long non-coding RNAs (lncRNAs) regulate embryonic development and cell fate decision in various ways, such as modulation of chromatin modification and post-transcription regulation of gene expression. However, the profiles and roles of lncRNAs in early mammalian development have not yet been demonstrated. Here, we reported a comprehensive analysis of mouse cleavage stage embryonic lncRNA profiles based on public single-cell RNA-seq data. RESULTS: We reconstructed 50,006 high-confidence transcripts in 22,827 loci, and identified 5563 novel lncRNAs from 3492 loci expressed in mouse cleavage stage embryos. These lncRNAs share similar characteristics with previously reported vertebrate lncRNAs, such as relatively short length, low exon number, low expression level and low sequence conservation. Expression profile analysis revealed that the profiles of lncRNA vary considerably at different stages of cleavage stage embryos, suggesting that many lncRNAs in cleavage stage embryos are stage-specifically expressed. Co-expression network analysis suggested many lncRNAs in cleavage stage embryos are associated with cell cycle regulation, transcription, translation and oxidative phosphorylation to regulate the process of cleavage stage embryonic development. CONCLUSIONS: This study provides the first catalog of lncRNAs expressed in mouse cleavage stage embryos and gives a revealing insight into the molecular mechanism responsible for early embryonic development.