Beyond the ß-amino alcohols framework: identification of novel ß-hydroxy pyridinium salt-decorated pterostilbene derivatives as bacterial virulence factor inhibitors.

BACKGROUND: Bacterial virulence factors are involved in various biological processes and mediate persistent bacterial infections. Focusing on virulence factors of phytopathogenic bacteria is an attractive strategy and crucial direction in pesticide discovery to prevent invasive and persistent bacterial infection. Hence, discovery and development of novel agrochemicals with high activity, low-risk, and potent anti-virulence is urgently needed to control plant bacterial diseases. RESULTS: A series of novel ß-hydroxy pyridinium cation decorated pterostilbene derivatives were prepared and their antibacterial activities against Xanthomonas oryzae pv. oryzae (Xoo) were systematacially assessed. Among these pterostilbene derivatives, compound 4S exhibited the best antibacterial activity against Xoo in vitro, with an half maximal effective concentration (EC50) value of 0.28 µg mL-1. A series of biochemical assays including scanning electron microscopy, crystal violet staining, and analysis of biofilm formation, swimming motility, and related virulence factor gene expression levels demonstrated that compound 4S could function as a new anti-virulence factor inhibitor by interfering with the bacterial infection process. Furthermore, the pot experiments provided convinced evidence that compound 4S had the high control efficacy (curative activity: 71.4%, protective activity: 72.6%), and could be used to effectively manage rice bacterial leaf blight in vivo. CONCLUSION: Compounds 4S is an attractive virulence factor inhibitor with potential for application in treating plant bacterial diseases by suppressing production of several virulence factors. © 2024 Society of Chemical Industry.

Prenatal diagnosis of fetal skeletal dysplasia using targeted next-generation sequencing: an analysis of 30 cases.

BACKGROUND: This study aims to provide genetic diagnoses for 30 cases of fetal skeletal dysplasia, and a molecular basis for the future prenatal diagnosis of fetal skeletal dysplasia. METHODS: A total of 30 cases of fetal skeletal dysplasia detected with ultrasound between January 2014 and June 2017 were analyzed. Among these fetuses, 15 fetuses had local skeletal malformations, while 15 fetuses had short limb malformations. Samples of fetal umbilical cord blood, amniotic fluid, and/or aborted tissue were collected from all cases. Karyotyping, whole genome sequencing, and targeted next-generation sequencing of skeletal disease-related pathogenic genes were performed, as needed. Blood samples were taken from the parents for verification using Sanger sequencing. RESULTS: Among the 30 cases of fetal skeletal dysplasia, two cases were diagnosed with trisomy 18. However, none of these cases were identified with any microdeletions or microreplications associated with skeletal dysplasia. Among the 28 chromosomally normal cases with fetal skeletal dysplasia, 21 cases were detected with mutations in genes related to skeletal diseases. Furthermore, collagen gene mutations were detected in six fetuses with short limb malformations, while heterozygous disease-causing mutations in the fibroblast growth factor receptor 3 (FGFR3) gene were detected in seven fetuses. The remaining fetuses carried mutations in other various genes, including tumor protein p63 (TP63), cholestenol delta-isomerase (EBP), cholinergic receptor nicotinic gamma subunit (CHRNG), filamin B (FLNB), and SRY-box 9 (SOX9). Three compound heterozygous mutations in CHRNG, COL11A2 and SOX9 were carried by phenotypically healthy parents. CONCLUSION: Targeted next-generation sequencing can significantly improve the prenatal diagnoses of fetal skeletal dysplasia, providing parents with more precision medicine, and improved genetic counseling.

Effect of antioxidants on amelioration of high-risk factors inducing hypertensive disorders in pregnancy.

BACKGROUND: This is a prospective clinical study based on a large sample gathered from multiple centers in China, subordinating to 10th Five-Year Plan of National Science & Technology Progression. We analyzed the high-risk factors inducing hypertensive disorders in pregnancy (HDP) and estimated the potential effect of anti-oxidants administration, including vitamin C (VC), vitamin E (VE) and Salvia Miltiorrhiza L (SML), a Chinese herb medicine, in amelioration of the high-risk factors in pregnancy. METHODS: From April 2005 to July 2006, 4814 pregnant women from 24 national wide cooperative hospitals were involved in this prospective research. The participants were randomly divided into two groups: 1607 cases were in anti-oxidants group with administration of vitamins and SML; 3207 cases were in control group without any medicine given. Every participant was under monitoring for the morbidity of HDP and the high-risk factors were investigated in HDP cases in each group. RESULTS: (1) The morbidity of HDP was 3.55% in anti-oxidants group vs. 4.18% in control group. No statistical difference existed between the two groups (P > 0.05). (2) In anti-oxidants group, the HDP morbidities among three subgroups: VC + VE + SML, VC + VE and SML only, were 5.51%, 3.05% and 5% respectively. It showed no statistical difference among three remedies (P > 0.05). (3) The related index of factors affecting HDP showed in intensity sequence as follows: family HDP history > profession > education level > age > body weight. The incidence of HDP in normal population was 3.51%, and the incidence of HDP in high-risk pregnant women (family HDP history, heavy physical labor, low education level (middle school and below), age ≥ 40, body mass index ≥ 24) was 5.84%, which was obviously higher than that in normal population (P < 0.01). In anti-oxidants group, the probability of HDP in women with high-risk factors was 3.81%, which was obviously lower than that in control group with high-risk factors at 7.14% (P < 0.01). (4) In control group, the morbidity of HDP in women with family HDP history (especially with sisters'), heavy physical labor, middle school and below, age ≥ 35 was: 50.00%, 15.22%, 6.33%, 26.28% and 5.75%, respectively, and that in anti-oxidants group was 0, 7.69%, 3.74%, 9.27% and 2.67%, respectively, which was obviously lower than that in control group. CONCLUSIONS: The high-risk factors prone to induce HDP included: family history of HDP, heavy physical labor, low education level, aging and obesity. No impressive effect of anti-oxidants application was found in preventing HDP in general population but the remedy demonstrated positive effect on preventing HDP in pregnant women with high-risk factors.

[The feeder layer of human embryonic fibroblasts supports the growth of human spermatogonial stem cells].

OBJECTIVE: To investigate the methods and conditions for the isolation, purification and culture of human spermatogonial stem cells (SSCs) on the feeder layer cells of human embryonic fibroblasts (hEFs). METHODS: SSCs isolated and purified from normal human fetal testicular tissues by sequential two-step enzyme digestion and Percoll uncontinuous density gradient centrifugation were cultured on the feeder layer cells of hEFs isolated from 5-9 weeks old human embryos. The surface markers SSEA-1 and OCT4 of the SSCs were detected by immunohistochemistry; the alkaline phosphatase (AKP) activity of the SSC clones measured; and the expressions of the SSC-related genes determined by RT-PCR. RESULTS: SSCs survived, proliferated and formed colonies on the feeder layers, and the colonies were highly positive for SSEA-1 and OCT4, with strong AKP activity and high expressions of the SSC-related genes. CONCLUSION: The feeder layer of hEFs supports the growth of human spermatogonial stem cells.