Accuracy of antibiotic concentrations in drug dispensing in neonates: a laboratory-based study.

BACKGROUND: Antibacterial therapy plays a crucial role in neonatal infections. The efficacy of antibacterial agents is closely related to the actual dose given to neonates. So we evaluated factors potentially affecting the actual dose of intravenous antibiotics during dispensing process in neonates. METHODS: Meropenem, cefoperazone/sulbactam and piperacillin/tazobactam with two strengths were used to evaluate three methods. Method A (MA) was diluted once and the volumes of 5% glucose for MA were meropenem 4.00 mL, cefoperazone/sulbactam 3.00 mL, piperacillin/tazobactam 9.00 mL. Method B (MB) differed by doubling the volume of 5% glucose. The difference in method C (MC) involved diluting with 5% glucose twice. The concentrations were measured by high-performance liquid chromatography. Relative error (RE) was used to evaluate the preparation accuracy. RESULTS: The RE values using MA/MB/MC were: (1) meropenem 0.5 g: 15.1%, 8.0%, 10.4%; 0.25 g: 7.8%, 3.1%, 6.0%; (2) cefoperazone/sulbactam 1.5 g: 13.6%, 4.2%, 3.4%; 0.75 g: 8.8%, 3.5%, 4.0%; (3) piperacillin/tazobactam 4.5 g: 18.2%, 8.7%, 6.3%; 562.5 mg: 8.1%, 2.8%, 6.1%. MB was better than MA in all three drugs. No difference in RE values was found between single and double dilution, except meropenem with 0.25 g. Using MB, meropenem and piperacillin/tazobactam with small drug strength had higher accuracy in preparation. CONCLUSIONS: MB was suitable for neonatal drug dispensing because of its high accuracy and simple operation. Drugs with small strength were promoted due to the high accuracy.

High-risk human papillomavirus distribution in different cytological classification women.

High-risk human papillomavirus (HR-HPV) infection is a major cause of infection-related cancer worldwide. 3101 HR-HPV-positive females were retrospectively analyzed and grouped using the cervical cytological screening (ThinPrep cytological test, TCT) evaluations combined with colposcopy. The HPV16 infection rate is the highest in all groups. HPV16 was the most frequent in each group, with significant differences between the four groups (χ2 = 23.41, P = 0.0001). The distribution of HPV16 and HPV33 correlated with the pathologic stage in each group. The mixed infection rate of mRNA testing differs significantly between groups (P < 0.01, χ2 = 17.44, P = 0.002). HR-HPV infection duration of less than six months accounted for 87.65%, 6 and 12 months of persistent infection (28.28%), and more than one year of continuous infection accounted for only 16.48%. The top three HPV types in a group with a duration of more than 12 months were HPV52 (3.03%), HPV16 (2.55%), and HPV39 (1.58%). The least clearance types were HPV39 (63.48%), 56 (69.54%), and 52 (71.44%) more than 12 months. This study revealed the region's primary pathogenic subtypes on different cervical lesions and provided the basis for diagnosing and treating HPV infection.

High-risk HPV prevalence and genotype distribution among women in Liaocheng, Shandong Province, China from 2016 to 2022.

Human papilloma virus (HPV) infection and its associated disease are major problems affecting millions of individuals around the world. The distribution of HPV genotypes is specific to different areas and different populations. Therefore, understanding the prevalence and genotype distribution of HPV in different populations in different geographical regions is essential to optimize HPV vaccination strategies and to maximize vaccine effects. In this study, 34,076 women from January 2016 to July 2022 were retrospectively analyzed at Liaocheng People's Hospital. Of these, 7540 women were high-risk HPV positive and the infection rate was 22.13%. The top ten genotypes were as follows in descending order: HPV16, HPV52, HPV58, HPV53, HPV39, HPV59, HPV66, HPV51, HPV18, and HPV56 and the least frequent genotypes were, in order, HPV 26, HPV45, and HPV82. The HPV16 positive infection rate was 25.37% and was reduced with the increase in the number of individuals who had undergone HPV screening. The HPV52 infection rate increased with increasing numbers of individuals undergoing HPV screening, and then remained unchanged. The proportion of 20-29-year-olds among all positive women began to decrease since the vaccine was available in 2018. The 30-39-year-old group accounted for the highest percentage of positive women, and the 50-59-year-old group of HPV-positive women with cervical cancer accounted for most infections. This study confirmed that HPV16, HPV52, HPV 58, and HPV53 is widely distributed in this population and the total HR-HPV infection rate remains high in this region. Our findings indicate that prevention of HPV infection in this region still faces important challenges.

Assessment of lake area in response to climate change at varying elevations: A case study of Mt. Tianshan, Central Asia.

Changes in lake area (water surface area) are often considered accurate and sensitive representations of climate change. However, the role that elevation plays in this dynamic is somewhat unclear; studies remain inconclusive as to whether lake responses are consistent across elevation gradients. Here, we used Landsat and keyhole satellite images to quantify lake area changes from the 1960s to 2020 at different elevations in Central Asia's Tianshan Mountains and relate them to both climatic and anthropogenic factors. The results revealed that all low-elevation lakes showed a decreasing trend, and the total area of all monitored low-elevation lakes was reduced by 18.50 %. The total area of the mid-elevation lakes decreased by 0.16 %, while the total area of the high-elevation glacial lakes increased by 4.35 %. Lakes are recharged by a variety of influxes including glacial meltwater and precipitation. Notably, human activities (urban and agricultural water consumption) were the dominant factors in the shrinkage of low-elevation lakes. Climatic factors were the main driving factors of mid-elevation lake changes, and these lakes appeared to be more sensitive to temperature changes than lakes at other elevations. In addition, significant warming dominated area changes in high-elevation proglacial and unconnected glacial lakes. Overall, those results emphasized that when using lakes to reconstruct paleoclimates or predict lake evolution, it is necessary to consider how elevation gradients and recharge types may affect lake sensitivity to variations in climatic and anthropogenic activity.

Pannier is a key regulator of embryogenesis, pupal development and female reproduction in the insect pest Bactrocera dorsalis.

BACKGROUND: Most arthropods are famous for their large reproductive capacity, with the ovary playing a vital role in the process. The study of the regulatory mechanisms of ovarian development may have the potential for a reproduction-based pest management strategy. GATA-binding transcription factors (GATAs) as important regulatory factors mediate many physiological processes, including development, immunity, insecticide resistance and reproduction. The Pannier (pnr), a member of GATA family, was confirmed to be involved in ovarian development of Bactrocera dorsalis in our previous study. However, the direct evidence of pnr regulating the fly ovarian development is still lacking. RESULTS: We used CRISPR/Cas9 to create Bdpnr loss-of-function mutations. Homozygous Bdpnr-/- mutants were nonviable, with most individuals dying during embryogenesis, some surviving to the larval stages, and the remaining few dying during pupation. In contrast, heterozygous individuals reached the adult stage, but ovarian development was disrupted, with concomitant decreases in egg laying and hatching rates. We also found that two genes encoding vitellogenin proteins (BdVg1 and BdVg2) and the vitellogenin receptor (BdVgR) were significantly down-regulated in heterozygous mutants compared to wild-type controls. CONCLUSION: These results indicate that Bdpnr is required for embryonic and post-embryonic development, including the formation of ovaries. Bdpnr could therefore be considered as a molecular target for tephritid fly pest control. © 2022 Society of Chemical Industry.

Diaminopimelic Acid Metabolism by Pseudomonadota in the Ocean.

Diaminopimelic acid (DAP) is a unique component of the cell wall of Gram-negative bacteria. It is also an important component of organic matter and is widely utilized by microbes in the world's oceans. However, neither DAP concentrations nor marine DAP-utilizing microbes have been investigated. Here, DAP concentrations in seawater were measured and the diversity of marine DAP-utilizing bacteria and the mechanisms for their DAP metabolism were investigated. Free DAP concentrations in seawater, from surface to a 5,000 m depth, were found to be between 0.61 µM and 0.96 µM in the western Pacific Ocean. DAP-utilizing bacteria from 20 families in 4 phyla were recovered from the western Pacific seawater and 14 strains were further isolated, in which Pseudomonadota bacteria were dominant. Based on genomic and transcriptomic analyses combined with gene deletion and in vitro activity detection, DAP decarboxylase (LysA), which catalyzes the decarboxylation of DAP to form lysine, was found to be a key and specific enzyme involved in DAP metabolism in the isolated Pseudomonadota strains. Interrogation of the Tara Oceans database found that most LysA-like sequences (92%) are from Pseudomonadota, which are widely distributed in multiple habitats. This study provides an insight into DAP metabolism by marine bacteria in the ocean and contributes to our understanding of the mineralization and recycling of DAP by marine bacteria. IMPORTANCE DAP is a unique component of peptidoglycan in Gram-negative bacterial cell walls. Due to the large number of marine Gram-negative bacteria, DAP is an important component of marine organic matter. However, it remains unclear how DAP is metabolized by marine microbes. This study investigated marine DAP-utilizing bacteria by cultivation and bioinformational analysis and examined the mechanism of DAP metabolism used by marine bacteria. The results demonstrate that Pseudomonadota bacteria are likely to be an important DAP-utilizing group in the ocean and that DAP decarboxylase is a key enzyme involved in DAP metabolism. This study also sheds light on the mineralization and recycling of DAP driven by bacteria.

d-Alanine Metabolism via d-Ala Aminotransferase by a Marine Gammaproteobacterium, Pseudoalteromonas sp. Strain CF6-2.

As the most abundant d-amino acid (DAA) in the ocean, d-alanine (d-Ala) is a key component of peptidoglycan in the bacterial cell wall. However, the underlying mechanisms of bacterial metabolization of d-Ala through the microbial food web remain largely unknown. In this study, the metabolism of d-Ala by marine bacterium Pseudoalteromonas sp. strain CF6-2 was investigated. Based on genomic, transcriptional, and biochemical analyses combined with gene knockout, d-Ala aminotransferase was found to be indispensable for the catabolism of d-Ala in strain CF6-2. Investigation on other marine bacteria also showed that d-Ala aminotransferase gene is a reliable indicator for their ability to utilize d-Ala. Bioinformatic investigation revealed that d-Ala aminotransferase sequences are prevalent in genomes of marine bacteria and metagenomes, especially in seawater samples, and Gammaproteobacteria represents the predominant group containing d-Ala aminotransferase. Thus, Gammaproteobacteria is likely the dominant group to utilize d-Ala via d-Ala aminotransferase to drive the recycling and mineralization of d-Ala in the ocean. IMPORTANCE As the most abundant d-amino acid in the ocean, d-Ala is a component of the marine DON (dissolved organic nitrogen) pool. However, the underlying mechanism of bacterial metabolization of d-Ala to drive the recycling and mineralization of d-Ala in the ocean is still largely unknown. The results in this study showed that d-Ala aminotransferase is specific and indispensable for d-Ala catabolism in marine bacteria and that marine bacteria containing d-Ala aminotransferase genes are predominantly Gammaproteobacteria widely distributed in global oceans. This study reveals marine d-Ala-utilizing bacteria and the mechanism of their metabolization of d-Ala. The results shed light on the mechanisms of recycling and mineralization of d-Ala driven by bacteria in the ocean, which are helpful in understanding oceanic microbial-mediated nitrogen cycle.

Targeting hexokinase 2 increases the sensitivity of oxaliplatin by Twist1 in colorectal cancer.

Colorectal cancer (CRC) is the third most malignant tumour worldwide, with high mortality and recurrence. Chemoresistance is one of the main factors leading to metastasis and poor prognosis in advanced CRC patients. By analysing the Gene Expression Omnibus data set, we found higher hexokinase 2 (HK2) expression levels in patients with metastatic CRC than in those with primary CRC. Moreover, we observed higher enrichment in oxaliplatin resistance-related gene sets in metastatic CRC than in primary CRC. However, the underlying relationship has not yet been elucidated. In our study, HK2 expression was significantly elevated in CRC patients. Gene set enrichment analysis (GSEA) revealed multi-drug resistance and epithelial-mesenchymal transition (EMT) pathways related to high HK2 expression. Our results showed that knockdown of HK2 significantly inhibited vimentin and Twist1 expression and promoted TJP1 and E-cadherin expression in CRC cells. Additionally, transcriptional and enzymatic inhibition of HK2 by 3-bromopyruvate (3-bp) impaired oxaliplatin resistance in vitro and in vivo. Mechanistically, HK2 interacts with and stabilized Twist1 by preventing its ubiquitin-mediated degradation, which is related to oxaliplatin resistance, in CRC cells. Overexpression of Twist1 reduced the apoptosis rate by HK2 knockdown in CRC cells. Collectively, we discovered that HK2 is a crucial regulator that mediates oxaliplatin resistance through Twist1. These findings identify HK2 and Twist1 as promising drug targets for CRC chemoresistance.

Methylation of the Promoter Region of the Tight Junction Protein-1 by DNMT1 Induces EMT-like Features in Multiple Myeloma.

The molecular alterations that initiate the development of multiple myeloma (MM) are not fully understood. Our results revealed that TJP1 was downregulated in MM and positively related to the overall survival of MM patients in The Cancer Genome Atlas (TCGA) database and patient samples. In parallel, cell adhesion capacity representing MM metastasis was decreased in MM patients compared with healthy samples, together with the significantly activated epithelial-to-mesenchymal transition (EMT) transcriptional-like patterns of MM cells. Further analyses demonstrated that TJP1 negatively regulated EMT and consequently positively regulated cell adhesion in MM from TCGA database and MM1s cells. Furthermore, the methylation level of each CpG site on the TJP1 promoter was negatively correlated with TJP1 expression levels. Quantitative real-time PCR and western blot assays demonstrated that methylase DNMT1 regulated the methylation of TJP1. Finally, treatment with a combination of the MM clinical medicine bortezomib, methylation inhibitor, or TJP1 overexpression significantly suppressed the viability and progression of tumor cells of MM orthotopic models. In summary, our results indicate that DNMT1 promotes the methylation of TJP1 promoter, thereby decreasing its expression and regulating the development of EMT-inhibited MM cell adhesion. Therefore, methylation of TJP1 is a potential therapeutic agent to prevent the progression of MM disease.

Effect of functional variant rs11466313 on breast cancer susceptibility and TGFB1 promoter activity.

PURPOSE: This study aimed to investigate whether genetic polymorphisms in TGFB1 contribute to breast cancer (BC) susceptibility, and explore the mechanism of action. METHODS: A total of 7 tagging SNPs (tSNPs) were genotyped in 1161 BC cases and 1337 age-matched controls among Chinese Han population. Bioinformatics analysis was used to predict functional SNP closely linked to tSNPs. Luciferase gene reporter assay was performed to determine the effect of genetic variants on promoter activity. DNA pull-down assay and mass spectrometry were used to identify the differentially binding proteins to genetic variants. RESULTS: Genotyping analysis showed that rs1800469 (C>T) in the 5' regulatory region of TGFB1 was associated with reduced BC risk. Bioinformatics analysis predicted that rs11466313 (-2389_-2391 Del/AGG) in the 5' regulatory region of TGFB1, was closely linked to tSNP rs1800469 and could be functional. The genotyping of rs11466313 by PCR-SSCP showed that rs11466313 also conferred decreased BC risk. Luciferase assays demonstrated that rs11466313 minor allele reduced over ninefold of promoter activity compared with its major allele (p < 0.001). DNA pull-down assay and mass spectrometry revealed that rs11466313 minor allele lost the binding ability with FAM98B and HSP90B. Knocking down FAM98B but not HSP90B, the enhanced promoter activity driven by TGFB1 rs11466313 major allele was attenuated. CONCLUSIONS: This study elucidates the impact of functional polymorphism rs11466313 in the regulatory region of TGFB1 on breast cancer susceptibility and gene expression, and could be helpful for future research to determine the value of this TGFB1 variant in the clinical setting.

[Post-stroke constipation treated with acupoint embedding therapy: a multi-center randomized controlled trial].

OBJECTIVE: To verify the clinical effect of acupoint embedding therapy on post-stroke constipation. METHODS: The multi-central randomized controlled trial was adopted. 210 patients of post-stroke constipation were divided into an acupoint embedding group (105 cases, 4 cases dropped off) and a sham-embedding group (105 cases, 6 cases dropped off). In the acupoint embedding group, the acupoint embedding therapy was used at Tianshu (ST 25), Daheng (SP 15), Xiawan (CV 10), Zhongwan (CV 12), Qihai (CV 6), Guanyuan (CV 4) and Daju (ST 27). In the sham-embedding group, the sham-embedding therapy was given, in which, the acupoint selection, needle devices and manipulation were the same as the acupoint embedding group. But, no absorbable surgical suture was used in the needle tube. The treatment was given once every two weeks and 4 treatments were required in either group. It was to compare the weekly average complete spontaneous bowel movements (CSBMs) during treatment (from the 3rd to the 8th week) between the two groups, the weekly average spontaneous bowel movements (SBMs), Bristol stool form score (BSFS), the score of the patient assessment of constipation quality of life questionnaire (PAC-QOL) and the score of defecation difficulty before and after treatment. RESULTS: The percentage of the cases with weekly average CSBMs ≥ 3 times in the patients of the acupoint embedding group was higher markedly than the sham-embedding group [91.1% (92/101) vs 43.4% (43/99), P<0.01]. Compared with the values before treatment, the weekly average SBMs and BSFS scores after treatment were all increased obviously in the two groups (P<0.01), and PAC-QOL score and the score of defecation difficulty were reduced remarkably (P<0.01). After treatment, the increase range of SBMs and BSFS scores, as well as the decrease range of PAC-QOL score and the defecation difficulty score in the acupoint embedding group were all higher than the sham-embedding group respectively (P<0.05). CONCLUSION: The acupoint embedding therapy remarkably increases the spontaneous bowel movements, improves in feces form and defecation difficulty and strengthens the quality of life in the patients of post-stroke constipation.

The Role of Spirituality in Patients Undergoing Hematopoietic Stem Cell Transplantation: a Systematic Mixed Studies Review.

BACKGROUND: Hematopoietic stem cell transplantation (HSCT) has become the standard treatment for many diseases, but it is an intense and distinctive experience for patients. HSCT-related mortality is present throughout the whole process of transplantation, from pretransplantation to recovery. Long-term rehabilitation and the uncertain risk of death evoke feelings of vulnerability, helplessness, and intense fear. Zimmermann et al. proposed that spiritual well-being is an important dimension of quality of life and that patients at the end stage of life require spiritual support in addition to physical care, psychological care, and social support. Therefore, the purpose of this review is to examine the role of spirituality in the process of HSCT. METHOD: A systematic mixed studies review (SMSR) was based on Pluye and Hong's framework to understand the role of spirituality in patients' experiences while undergoing HSCT. We use the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement to report the results of integration. RESULTS: Fifteen original qualitative studies, 19 quantitative studies, and one mixed method study were included in the systematic mixed studies review. The evidence from the review revealed the following three themes: the spiritual experiences of HSCT patients, the spiritual coping styles of HSCT patients, and the spiritual need changes brought about by HSCT. DISCUSSION: Few medical institutions currently offer spiritual healing, although HSCT patients with different cultural backgrounds may have different spiritual experiences and spiritual coping styles. Psychotherapists or nurses should be considered to provide spiritual care for patients undergoing HSCT, to help patients cope with disease pressures, promote HSCT patients' comfort, and improve their quality of life.

Nurses' knowledge of the management of drug-induced peripherally inserted central catheter obstruction: A descriptive phenomenological study.

OBJECTIVES: The purpose of this research is to describe and understand nurses' knowledge of drug-induced peripherally inserted central catheter obstruction management in developing countries. This research aims to identify the reasons why nurses lack knowledge of the management of drug-induced peripherally inserted central catheter obstruction and do not use the drug-induced peripherally inserted central catheter obstruction management techniques recommended by the Infusion Therapy Standards of Practice. METHODS: The descriptive phenomenological method was used to investigate nurses' knowledge of the management of drug-induced peripherally inserted central catheter obstruction. Semi-structured in-depth interviews with 17 nurses from three hospitals in northeast China were used in this qualitative study. Data collection and analysis were conducted simultaneously during the research. Nvivo software 12.0 was used to organize and code the data, and Colaizzi's seven phases of data analysis were used to form themes. FINDINGS: The findings showed that there is inconsistency in nurses' knowledge of drug-induced peripherally inserted central catheter obstruction and its management, and we suggest reasons for this phenomenon. CONCLUSION: This research has shown that inconsistent practice in the management of drug-induced peripherally inserted central catheter obstruction is a more complex issue than originally thought. These inconsistencies are related to time pressure on nurses, nurses' knowledge of peripherally inserted central catheter obstruction, and limitations of the clinical work model.

Effects of enteral nutritional rich in n-3 polyunsaturated fatty acids on the nutritional status of gastrointestinal cancer patients: a systematic review and meta-analysis.

Postoperative malnutrition is a major issue among gastrointestinal cancer patients. Because n-3 polyunsaturated fatty acids (n-3 PUFAs) have immunological benefits, n-3 PUFAs are widely used in oral nutritional supplements (ONS). However, n-3 PUFAs in ONS reduced patients' compliance with ONS and affected the role of ONS in maintaining the postoperative nutritional status of patients. The aim of this study was to systematically explore the benefits of enteral nutrition rich in n-3 PUFAs in maintaining the nutritional status of patients after gastrointestinal surgery. Databases including PubMed, Web of Science, Embase, Cochrane Library, China National Knowledge Infrastructure, Wanfang, and VIP databases were searched through March 16, 2019. The references of related reviews and studies were assessed up to March 16, 2019. The effect sizes from individual studies were calculated as the standardized mean difference (SMD), mean difference (MD), and risk ratio (RR) with 95% confidence intervals (95% CIs). A total of 11 studies (n = 977) were included. In this systematic review and meta-analysis, we observed that enteral supplementation of n-3 PUFAs had no significant effect on weight (MD, 1.09; 95% CI, -0.90, 3.08), body mass index (MD, 0.55; 95% CI, -1.45, 2.54), albumin (SMD, 0.39; 95% CI, -0.10, 0.87), wound infections (RR, 0.87, 95% CI, 0.57, 1.33), or pneumonia (RR, 0.98; 95% CI, 0.60, 1.59) in gastrointestinal cancer patients. Thus, compared with enteral nutritional without n-3 PUFAs, enteral nutritional rich in n-3 PUFAs has no significant effects on nutritional status, incidence of pneumonia, or wound infections among gastrointestinal cancer patients during postoperative convalescence.

Efficacy of management for obstruction caused by precipitated medication or lipids in central venous access devices: A systematic review and meta-analysis.

At present, central venous access devices (CVADs) are widely used in clinical practice. The reasons for CVAD obstruction caused by precipitated medication or lipids are increasingly complex. However, there is no clear treatment program for CVAD obstruction caused by precipitated medication or lipids. The target of this study was to analyze data regarding obstruction caused by precipitated medication or lipids in CVADs and to calculate the efficacy of different treatment methods. A systematic review with meta-analysis was conducted in alignment with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. The PubMed, Web of Science, EMBASE, Cochrane Library, CINAHL, and China National Knowledge Internet databases were searched for original research published before 2018. There were 1356 publications initially screened, with one additional study identified through snowballing. Seven studies met the inclusion criteria. The reasons for obstruction, except for clot formation, primarily included the following: mechanical complications; lipid deposition; mineral deposition; or drug precipitation. Meta-analysis showed that sodium hydroxide resulted in the highest recanalization rate in lipid deposition, followed by ethanol, and the difference was significant. The efficacy analysis revealed that hydrochloric acid and l-cysteine have similar effects on mineral deposition and drug precipitation. According to this review, the most effective methodology was shown to be the intravenous perfusion of sodium hydroxide in several treatments when the obstruction is caused by lipid deposition. In contrast, mineral deposition and drug deposition are best treated with l-cysteine to recover the patency of central venous access devices.

Diversity of D-Amino Acid Utilizing Bacteria From Kongsfjorden, Arctic and the Metabolic Pathways for Seven D-Amino Acids.

D-amino acids (DAAs) are an important component of the refractory dissolved organic matter pool in the ocean. Microbes play a vital role in promoting the recycling of DAAs in the ocean. However, the diversity of marine DAA-utilizing bacteria and how they metabolize DAAs are seldom studied. Here, by enrichment culture with DAAs as the sole nitrogen source, bacteria of 12 families from three phyla were recovered from surface seawater and sediment from Kongsfjorden, Arctic, and seven DAA-utilizing bacterial strains were isolated. These strains have different DAA-utilizing abilities. Of the seven DAAs used, Halomonas titanicae SM1922 and Pseudoalteromonas neustonica SM1927 were able to utilize seven and five of them, respectively, while the other strains were able to utilize only one or two. Based on genomic, transcriptional and biochemical analyses, the key genes involved in DAA metabolism in each strain were identified and the metabolic pathways for the seven DAAs in these marine bacteria were identified. Conversion of DAAs into α-keto acids is generally the main pathway in marine DAA-utilizing bacteria, which is performed by several key enzymes, including DAA oxidoreductases/dehydrogenases, D-serine ammonia-lyases, D-serine ammonia-lyase DSD1s and DAA transaminases. In addition, conversion of DAAs into LAAs is another pathway, which is performed by amino acid racemases. Among the identified key enzymes, D-serine ammonia-lyase DSD1 and Asp racemase are first found to be employed by bacteria for DAA utilization. These results shed light on marine DAA-utilizing bacteria and the involved DAA metabolism pathways, offering a better understanding of the DAA recycling in the ocean.

Genetic polymorphisms in CDH1 are associated with endometrial carcinoma susceptibility among Chinese Han women.

The cadherin 1 (CDH1) gene plays critical roles in the epithelial-mesenchymal transition process, potentially offering us a glimpse into the development of endometrial carcinoma (EC). The present study aimed to identify whether genetic variants in CDH1 affect EC susceptibility in Chinese Han women, using a strategy combining haplotype-tagging single nucleotide polymorphisms (htSNPs) association analysis with fine-scale mapping. A total of 9 htSNPs in CDH1 were genotyped among 516 cases and 706 age-matched cancer-free controls. Logistic regression analyses revealed 3 htSNPs (rs17715799, rs6499199 and rs13689) to be associated with increased EC risk and 3 htSNPs (rs12185157, rs10431923 and rs4783689) with decreased EC risk. Furthermore, 14 newly imputed SNPs of CDH1 were identified to be associated with EC risk (P<0.05) using genotype imputation analysis. Notably, multivariate logistic analysis demonstrated that rs13689, rs10431923 and rs10431924 could affect EC susceptibility independently (P≤0.001). Subsequent Generalized Multifactor Dimensionality Reduction analysis revealed several best fitting models for predicting EC risk, including SNP-SNP interactions among rs7100190, rs12185157, rs10431923, rs7186053, rs6499199, rs4783689, rs13689, rs6499197 and rs10431924, and SNP-environment interactions between related SNPs and number of childbirth. Moreover, functional annotations suggest that the majority of these susceptible variants may carry potential biological functions that affect certain gene regulatory elements. In summary, this study suggested that the genetic polymorphisms of CDH1 were indeed associated with EC susceptibility on several levels. If further additional functional studies could verify these findings, these genetic variants may serve as future personalized markers for the early prediction of endometrial cancer in Chinese Han women.

Associations of gene­wide SNPs in SNAI1 and TWIST1 with breast cancer and ovarian cancer susceptibility among Chinese Han women.

Extensive evidence suggests that the genetic etiologies of breast cancer (BC) and ovarian cancer (OC) show a certain degree of similarity. This study aimed to find out whether the single nucleotide polymorphisms (SNPs) of genes SNAI1 and TWIST1 may affect BC and OC susceptibility. A total of 7 tagging­SNPs (tSNPs) were directly genotyped in 1,161 BC cases, 286 OC cases and 1,273 cancer­free controls among Chinese Han women. Twenty­eight variants in these 2 genes were genotyped by 'in silico' genotype imputation. Logistic regression (LR) revealed that tSNPs SNAI1 rs6125849, TWIST1 rs4721746 and TWIST1 rs4721745 were protective genetic variants for BC/OC. Allelic association tests of gene­wide SNPs demonstrated that the minor alleles of SNAI1 rs6125849, TWIST1 rs4721745 and TWIST1 rs11973396 were strongly associated with BC/OC susceptibility. Multivariate LR presented that SNAI1 rs6125849, TWIST1 rs4721745, rs4721746 and rs11973396 affected BC/OC susceptibility independently, and women harboring all four protective genoytpes had the lowest risk. Multifactor dimensionality reduction analysis further showed that SNAI1 rs6125849 and TWIST1 rs4721745 had the strongest synergistic interaction. Functional annotation predicted that the minor alleles of SNAI1 rs6125849 and TWIST1 rs4721745 altered their binding affinities with transcription factors E2F6 and TCF11­MafG respectively. These results indicate that genetic variants in SNAI1 and TWIST1, most probably SNAI1 rs6125849 and TWIST1 rs4721745, may modulate BC and OC susceptibility.

Genetic Polymorphisms of TGFB1, TGFBR1, SNAI1 and TWIST1 Are Associated with Endometrial Cancer Susceptibility in Chinese Han Women.

Endometrial cancer (EC) is a complex disease involving multiple gene-gene and gene-environment interactions. TGF-ß signaling plays pivotal roles in EC development. This study aimed to investigate whether the genetic polymorphisms of TGF-ß signaling related genes TGFB1, TGFBR1, SNAI1 and TWIST1 contribute to EC susceptibility. Using the TaqMan Genotyping Assay, 19 tagging-SNPs of these four genes were genotyped in 516 EC cases and 707 controls among Chinese Han women. Logistic regression (LR) showed that the genetic variants of TGFB1 rs1800469, TGFBR1 rs6478974 and rs10733710, TWIST1 rs4721745 were associated with decreased EC risk, and these four loci showed a dose-dependent effect (Ptrend < 0.0001). Classification and regression tree (CART) demonstrated that women carrying both the genotypes of TGFBR1 rs6478974 TT and rs10512263 TC/CC had the highest risk of EC (aOR = 7.86, 95% CI = 3.42-18.07, P<0.0001). Multifactor dimensionality reduction (MDR) revealed that TGFB1 rs1800469 plus TGFBR1 rs6478974 was the best interactional model to detect EC risk. LR, CART and MDR all revealed that TGFBR1 rs6478974 was the most important protective locus for EC. In haplotype association study, TGFBR1 haplotype CACGA carrier showed the lowest EC risk among women with longer menarche-first full term pregnancy intervals (˃11 years) and BMI˂24 (aOR = 0.39, 95% CI = 0.17-0.90, P = 0.0275). These results suggest that polymorphisms in TGFB1, TGFBR1, SNAI1 and TWIST1 may modulate EC susceptibility, both separately and corporately.

Association of genetic polymorphisms in AURKA, BRCA1, CCNE1 and CDK2 with the risk of endometrial carcinoma and clinicopathological parameters among Chinese Han women.

OBJECTIVE: Centrosome aberrations and cell-cycle deregulations have important implications for the development of endometrial carcinoma. AURKA, BRCA1, CCNE1 and CDK2 genes play pivotal roles in centrosome duplication and cell-cycle regulation. This study aimed to investigate whether genetic polymorphisms in these four genes may contribute to endometrial carcinoma susceptibility and progression in Chinese Han women. STUDY DESIGN: A total of twenty-two single nucleotide polymorphisms (SNPs) were selected according to the public HapMap database (HapMap Data Release #27; Chinese Beijing population), and genotyped using TaqMan Realtime PCR method in 530 endometrial adenocarcinoma cases and 825 age-matched controls from Chinese Han women. Then, haplotype blocks were reconstructed according to our genotyping data. RESULTS: For AURKA, the rs911162 was associated with increased risk of endometrial carcinoma [in co-dominant model: adjusted odds ratio (aOR) = 4.92, 95% CI = 1.24-19.55, P = 0.0235]. The haplotype GA (rs6064391 + rs911162) in block 1 of AURKA was also associated with increased risk of endometrial carcinoma (aOR = 1.25, 95% CI = 1.07-2.06, P = 0.0189). For BRCA1, the minor allele homozygotes of rs8067269 could decrease the risk of endometrial carcinoma (in co-dominant models: aOR = 0.52, 95% CI = 0.34-0.80, P = 0.0032), so was the haplotype CTCAG (rs8176323 + rs8176199 + rs3737559 + rs8067269 + rs2070833) (aOR = 0.69, 95% CI = 0.50-0.95, P = 0.0234). Moreover, we found several associations between genetic variations in CCNE1, BRCA1 and AURKA and clinicopathological parameters. CONCLUSIONS: This study indicates that genetic polymorphisms of AURKA, BRCA1 and CCNE1 may contribute to endometrial carcinoma susceptibility or progression in Chinese Han women.