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Here, we present a Han Chinese pediatric girl highly suspected of congenial disorder of glycosylation type IIL (CDG2L; OMIM#614576). Her clinical symptoms include transferase abnormal, liver cirrhosis, hemogram, coagulopathy, growth retardation, intellectual disability, frequent infections, and enamel hypoplasia. Trio-genome sequencing identified in COG6 a paternal variant c.1672C>T (p.Gln558Ter) and a maternal variant c.153+392A>G (p.?). Reverse transcription-polymerase chain reaction (RT-PCR) using mRNA isolated from peripheral blood confirmed the pathogenicity of both variants. The paternal variant resulted in nonsense-mediated mRNA decay. The maternal variant generated two aberrant COG6 transcripts with 154 bp overlap and was predicted to result in a frameshift at the same position, leading to generation of a premature termination codon. They might result in synthesis of a truncated form of COG6. Thus, the patient was genetically diagnosed. [ABSTRACT FROM AUTHOR]

Radiotherapy, as an important primary treatment, has effectively improved the survival of patients with cervical cancer (CC). Some patients, however, do not benefit optimally from radiotherapy because of radio‐resistance. Therefore, identifying radio‐resistance biomarkers and unravelling the underlying mechanisms is of critical importance for these patients. In the present study, we found significant upregulation of hepatocyte nuclear factor 1‐alpha (HNF1α) expression in radio‐resistant cervical cancer tissues and cell lines. Depletion of HNF1α reduced and overexpression of HNF1α promoted the resistance of CC cells to irradiation in vitro and in vivo. HNF1α positively regulated DNA repair protein RAD51 homologue 4 (RAD51D) at the protein level but not at the mRNA level. Mechanistically, upregulation of HNF1α enhanced YTH domain‐containing family protein 3 (YTHDF3) transcription, which in turn promoted RAD51D mRNA N6‐methyladenosine (m6A) modification. YTHDF3 mediates HNF1α regulation of cervical cancer radio‐resistance by promoting RAD51D translation in an m6A‐dependent manner. The HFN1α/YTHDF3/RAD51D regulatory axis was found to play a critical role in conferring radio‐resistance of CC cells. In conclusion, dysregulation of the HFN1α/YTHDF3/RAD51D axis may promote the radio‐resistance of CC cells. Blocking this pathway may provide therapeutic benefits against CC radio‐resistance. [ABSTRACT FROM AUTHOR]

Background: While colorectal polyps are not cancerous, some types of polyps, known as adenomas, can develop into colorectal cancer over time. Polyps can often be found and removed by colonoscopy; however, this is an invasive and expensive test. Thus, there is a need for new methods of screening patients at high risk of developing polyps., Aim: To identify a potential association between colorectal polyps and small intestine bacteria overgrowth (SIBO) or other relevant factors in a patient cohort with lactulose breath test (LBT) results., Methods: A total of 382 patients who had received an LBT were classified into polyp and non-polyp groups that were confirmed by colonoscopy and pathology. SIBO was diagnosed by measuring LBT-derived hydrogen (H) and methane (M) levels according to 2017 North American Consensus recommendations. Logistic regression was used to assess the ability of LBT to predict colorectal polyps. Intestinal barrier function damage (IBFD) was determined by blood assays., Results: H and M levels revealed that the prevalence of SIBO was significantly higher in the polyp group than in the non-polyp group (41% vs 23%, P < 0.01; 71% vs 59%, P < 0.05, respectively). Within 90 min of lactulose ingestion, the peak H values in the adenomatous and inflammatory/hyperplastic polyp patients were significantly higher than those in the non-polyp group ( P < 0.01, and P = 0.03, respectively). In 227 patients with SIBO defined by combining H and M values, the rate of IBFD determined by blood lipopolysaccharide levels was significantly higher among patients with polyps than those without (15% vs 5%, P < 0.05). In regression analysis with age and gender adjustment, colorectal polyps were most accurately predicted with models using M peak values or combined H and M values limited by North American Consensus recommendations for SIBO. These models had a sensitivity of ≥ 0.67, a specificity of ≥ 0.64, and an accuracy of ≥ 0.66., Conclusion: The current study made key associations among colorectal polyps, SIBO, and IBFD and demonstrated that LBT has moderate potential as an alternative noninvasive screening tool for colorectal polyps., Competing Interests: Conflict-of-interest statement: The authors have no conflicts of interest to declare. There are no ethical or legal conflicts involved in the article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Based on RS and GIS, 11 indexes from three aspects including natural capital, social pressure and economic supports were selected. The natural capital index (NCI), social pressure index (SPI), economic support index (ESI), and environment quality evaluation index (EQEI) were constructed by using spatial principal component analysis, variation coefficient method, and analytic hierarchy process. The spatial distribution characteristics and influencing factor of the environmental quality in Shiyang River Basin were analyzed. The results showed that the overall environmental quality was at poor level in Shiyang River Basin. The regions with better classes of environmental quality were mainly concentrated in the upper reaches of Qilian Mountains, and those with poorer classes were mainly concentrated in the middle-lower reaches of low hills land and desert. The EQEI value in Shiyang River Basin had polarization phenomenon from southwest to northeast. With the variation of distance, the value had large variation range, with obvious spatial heterogeneity. The environmental quality showed both high and low aggregation patterns, with "fault" distribution. There were highly clustered hot spots and highly clustered cold spots in the basin. Among the influen-cing factors of environmental quality, natural capital was the dominant one, social pressure was the second, and economic support was the least contributor.

Drug metabolism studies, including in vivo and in vitro metabolism studies, are significant in the design of candidate compounds and screening of lead compounds at drug discovery/development stages. Compared with in vivo metabolism studies, in vitro metabolism studies have the advantages of rapidity, simplicity, without consumption of large amounts of samples and animals. Moreover, it is convenient for researchers to observe the selective interaction between compound and target. Therefore, in vitro metabolism studies are appropriate for high throughput screening of compounds which are lack of metabolism information and have been widely used during drug discovery stages. This article briefly introduced the application of in vitro drug metabolism studies based on the metabolic stability, reaction phenotyping and metabolic drug-drug interactions, aiming to raise valuable evaluation strategies for innovative drug discovery in China.