Enantioselective biomarkers of maize toxicity induced by hexabromocyclododecane based on submicroscopic structure, gene expression and molecular docking.

Hexabromocyclododecane (HBCD), as a monitored chemical of the Chemical Weapons Convention, the Stockholm Convention and the Action Plan for New Pollutants Treatment in China, raises significant concerns on its impact of human health and food security. This study investigated enantiomer-specific biomarkers of HBCD in maize (Zea mays L.). Upon exposure to HBCD enantiomers, the maize root tip cell wall exhibited thinning, uneven cell gaps, and increased deposition on the cell outer wall. Elevated malondialdehyde (MDA) indicated lipid peroxidation, with higher mitochondrial membrane potential (MMP) inhibition in (+)-enantiomer treatments (47.2%-57.9%) than (-)-enantiomers (14.4%-37.4%). The cell death rate significantly increased by 37.7%-108.8% in roots and 16.4%-62.4% in shoots, accompanied by the upregulation of superoxide dismutase isoforms genes. Molecular docking presenting interactions between HBCD and target proteins, suggested that HBCD has an affinity for antioxidant enzyme receptors with higher binding energy for (+)-enantiomers, further confirming their stronger toxic effects. All indicators revealed that oxidative damage to maize seedlings was more severe after treatment with (+)-enantiomers compared to (-)-enantiomers. This study elucidates the biomarkers of phytotoxicity evolution induced by HBCD enantiomers, providing valuable insights for the formulation of more effective policies to safeguard environmental safety and human health in the future.

The comparison between fixed versus degressive doses of medroxyprogesterone acetate combined with letrozole in patients of progestin-primed ovarian stimulation protocol: a propensity score-matched study.

Objective: To explore the cycle characteristics and pregnancy outcomes of progestin-primed ovarian stimulation (PPOS) using fixed versus degressive doses of medroxyprogesterone acetate (MPA) in conjunction with letrozole (LE) in infertile women by propensity score matching (PSM) analysis. Design: A retrospective cohort study. Setting: Tertiary-care academic medical center. Population: A total of 3173 infertile women undergoing their first in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment within the period from January 2017 to December 2020. Methods: A total of 1068 and 783 patients who underwent a fixed dose of MPA combined with LE and a degressive dose of MPA combined with LE protocols, respectively, were enrolled in this study. The freeze-all approach and later frozen-thawed embryo transfer (FET) were performed in both groups. Propensity score matching (1:1) was performed. Main outcome measures: The primary outcomes were the dosage of MPA and the incidence of premature luteinizing hormone (LH) surges. The secondary outcomes were the number of oocytes retrieved, the cumulative live birth rate (CLBR) and the fetal malformation rate. Results: We created a perfect match of 478 patients in each group. The dosage of MPA, the LH serum level on the eighth day of stimulation, progesterone (P) level and LH level on the hCG trigger day were significantly higher in the LE + fixed MPA group than in the LE + degressive MPA group (52.1 ± 13.1 mg vs. 44.9 ± 12.5 mg; 5.0 ± 2.7 IU/L vs. 3.7 ± 1.7 IU/L; 0.9 ± 0.5 ng/ml vs. 0.8 ± 0.5 ng/ml; 3.3 ± 2.4 IU/L vs. 2.8 ± 1.9 IU/L; P < 0.01). The duration of Gn, the number of follicles with diameter more than 16 mm on trigger day, the estradiol (E2) level on the hCG trigger day were lower in the LE + fixed MPA group than in the LE + degressive MPA group (9.7 ± 1.7 days vs. 10.3 ± 1.5 days; 5.6 ± 3.0 vs. 6.3 ± 3.0; 1752.5 ± 1120.8 pg/ml vs. 1997.2 ± 1108.5 pg/ml; P < 0.001). No significant difference was found in the incidence of premature LH surge, the number of oocytes retrieved, the number of top-quality embryos, clinical pregnancy rate (CPR), CLBR or fetal malformation rate between the two groups. Conclusion: The combination of a degressive MPA dose with LE proved effective in reducing the total MPA dosage with comparable premature LH surge and pregnancy outcomes in women undergoing the PPOS protocol.

Predictive validation of existing bleeding and thromboembolic scores in elderly patients with comorbid atrial fibrillation and acute coronary syndrome.

BACKGROUND: The validation of various risk scores in elderly patients with comorbid atrial fibrillation (AF) and acute coronary syndrome (ACS) has not been reported. The present study compared the predictive performance of existing risk scores in these patients. METHODS: A total of 1252 elderly patients with AF and ACS comorbidities (≥ 65 years old) were consecutively enrolled from January 2015 to December 2019. All patients were followed up for one year. The predictive performance of risk scores in predicting bleeding and thromboembolic events was calculated and compared. RESULTS: During the 1-year follow-up, 183 (14.6%) patients had thromboembolic events, 198 (15.8%) patients had BARC class ≥ 2 bleeding events, and 61 (4.9%) patients had BARC class ≥ 3 bleeding events. For the BARC class ≥ 3 bleeding events, discrimination of the existing risk scores was low to moderate, PRECISE-DAPT (C-statistic: 0.638, 95% CI: 0.611-0.665), ATRIA (C-statistic: 0.615, 95% CI: 0.587-0.642), PARIS-MB (C-statistic: 0.612, 95% CI: 0.584-0.639), HAS-BLED (C-statistic: 0.597, 95% CI: 0.569-0.624) and CRUSADE (C-statistic: 0.595, 95% CI: 0.567-0.622). However, the calibration was good. PRECISE-DAPT showed a higher integrated discrimination improvement (IDI) than PARIS-MB, HAS-BLED, ATRIA, and CRUSADE (P < 0.05) and the best decision curve analysis (DCA). For thromboembolic events, the discrimination of GRACE (C-statistic: 0.636, 95% CI: 0.608-0.662) was higher than CHA2DS2-VASc (C-statistic: 0.612, 95% CI: 0.584-0.639), OPT-CAD (C-statistic: 0.602, 95% CI: 0.574-0.629) and PARIS-CTE (C-statistic: 0.595, 95% CI: 0.567-0.622). The calibration was good. Compared to OPT-CAD and PARIS-CTE, the IDI of the GRACE score slightly improved (P < 0.05). However, NRI analysis showed no significant difference. DCA showed that the clinical practicability of thromboembolic risk scores was similar. CONCLUSIONS: The discrimination and calibration of existing risk scores in predicting 1-year thromboembolic and bleeding events were unsatisfactory in elderly patients with comorbid AF and ACS. PRECISE-DAPT showed higher IDI and DCA than other risk scores in predicting BARC class ≥ 3 bleeding events. The GRACE score showed a slight advantage in predicting thrombotic events.

Abnormal alanine aminotransferase levels in patients with moderate or severe ovarian hyperstimulation result in an increased risk of obstetric complications.

OBJECTIVES: To explore the effect of abnormally elevated serum alanine aminotransferase (ALT) on pregnancy outcomes in patients with moderate and severe ovarian hyperstimulation syndrome (OHSS) at disease onset. METHODS: This was a single-center retrospective cohort study conducted between January 1, 2014 and October 31, 2021. A total of 3550 fresh in vitro fertilization/intracytoplasmic sperm injection embryo transfer cycles were included, using Golan's three-degree, five-level classification to diagnose patients with OHSS. According to the patient's ALT level after diagnosis of OHSS, 123 (3.46%) patients with moderate-to-severe OHSS were divided into two groups. A control group included 3427 (96.54%) non-OHSS patients, and 91 (2.56%) abnormal ALT patients were matched with the control group for propensity scores. RESULTS: There was no difference in baseline data between the abnormal ALT and matched control groups. The incidence of obstetric complications was significantly higher in the abnormal ALT group than in the matched control group (P < 0.05). After adjusting for confounding factors, the incidence of obstetric complications in the abnormal ALT group was still higher than that in the normal ALT group (P < 0.05). CONCLUSION: In patients with moderate and severe OHSS, higher ALT levels resulted in an increased risk of obstetric and neonatal complications.

Methane emission reduction oriented extracellular electron transfer and bioremediation of sediment microbial fuel cell: A review.

Sediment is the internal and external source of water environment pollution, so sediment remediation is the premise of water body purification. Sediment microbial fuel cell (SMFC) can remove the organic pollutants in sediment by electroactive microorganisms, compete with methanogens for electrons, and realize resource recycling, methane emission inhibiting and energy recovering. Due to these characteristics, SMFC have attracted wide attention for sediment remediation. In this paper, we comprehensively summarized the recent advances of SMFC in the following areas: (1) The advantages and disadvantages of current applied sediment remediation technologies; (2) The basic principles and influencing factors of SMFC; (3) The application of SMFC for pollutant removal, phosphorus transformation and remote monitoring and power supply; (4) Enhancement strategies for SMFC in sediments remediation such as SMFC coupled with constructed wetland, aquatic plant and iron-based reaction. Finally, we have summarized the drawback of SMFC and discuss the future development directions of applying SMFC for sediment bioremediation.

MiR-130a-3p regulates FUNDC1-mediated mitophagy by targeting GJA1 in myocardial ischemia/reperfusion injury.

Understanding the complex pathogenesis in myocardial ischemia/reperfusion (I/R) injury (IRI) is an urgent problem in clinical trials. Increasing pieces of evidence have suggested that miRNAs are involved in the occurrence and development of heart diseases by regulating mitochondria-related gene expression. Mitochondria have been acknowledged as the key triggers of cardiac I/R injury. However, the potential impact of miR-130a on mitochondria remains unclear in myocardial IRI. Exploring the regulatory mechanism of miR-130a on mitochondria may provide a new target for IRI therapy. In the present study, we found that miR-130a significantly increased in acute myocardial infarction (AMI) patients and myocardial I/R rats. MiR-130a could downregulate the viability of cardiomyocytes and the knockdown of miR-130a could protect the viability of cardiomyocytes under hypoxia-reoxygenation (HR). Over-expression of miR-130a resulted in mitochondrial dysfunction. It was evidenced by decreases in mitochondrial ATP production, mitochondrial membrane potential (MMP), and an increase in reactive oxygen species (ROS) production. However, suppression of miR-130a could protect against mitochondrial damage, show elevation of mitochondrial ATP production rate and MMP, and reduce ROS production. We further explored the effect of miR-130a on the mitochondrial quality control (QMC) system by determining mitochondrial-protein-specific proteases and analyzed mitochondrial morphology by fluorescence imaging and electron microscopy, respectively. It was noted that miR-130a could suppress mitochondrial fusion and FUNDC1-mediated mitophagy to accelerate myocardial IRI. Moreover, we investigated the potential miR-130a targeted mitochondria-related genes to understand the regulatory mechanism of miR-130a in the setting of myocardial IRI. It was revealed that miR-130a targeted GJA1, and GJA1 rescued IRI by enhancing ATP production rate and oxidative phosphorylation, meanwhile protecting cell viability, MMP, and activating mitophagy. In addition, the knockdown of miR-130a significantly activated FUNDC1-mediated mitophagy, while the knockdown of GJA1 reversed the relevant response. Collectively, our findings suggest that miR-130a regulates FUNDC1-mediated mitophagy by targeting GJA1 in myocardial IRI.

Sex differences in the oral microbiome, host traits, and their causal relationships.

The oral microbiome has been implicated in a growing number of diseases; however, determinants of the oral microbiome and their roles remain elusive. Here, we investigated the oral (saliva and tongue dorsum) metagenome, the whole genome, and other omics data in a total of 4,478 individuals and demonstrated that the oral microbiome composition and its major contributing host factors significantly differed between sexes. We thus conducted a sex-stratified metagenome-genome-wide-association study (M-GWAS) and identified 11 differential genetic associations with the oral microbiome (p sex-difference  < 5 × 10-8). Furthermore, we performed sex-stratified Mendelian randomization (MR) analyses and identified abundant causalities between the oral microbiome and serum metabolites. Notably, sex-specific microbes-hormonal interactions explained the mostly observed sex hormones differences such as the significant causalities enrichments for aldosterone in females and androstenedione in males. These findings illustrate the necessity of sex stratification and deepen our understanding of the interplay between the oral microbiome and serum metabolites.

The Spatial Organization of Bacterial Transcriptional Regulatory Networks.

The transcriptional regulatory network (TRN) is the central pivot of a prokaryotic organism to receive, process and respond to internal and external environmental information. However, little is known about its spatial organization so far. In recent years, chromatin interaction data of bacteria such as Escherichia coli and Bacillus subtilis have been published, making it possible to study the spatial organization of bacterial transcriptional regulatory networks. By combining TRNs and chromatin interaction data of E. coli and B. subtilis, we explored the spatial organization characteristics of bacterial TRNs in many aspects such as regulation directions (positive and negative), central nodes (hubs, bottlenecks), hierarchical levels (top, middle, bottom) and network motifs (feed-forward loops and single input modules) of the TRNs and found that the bacterial TRNs have a variety of stable spatial organization features under different physiological conditions that may be closely related with biological functions. Our findings provided new insights into the connection between transcriptional regulation and the spatial organization of chromosome in bacteria and might serve as a factual foundation for trying spatial-distance-based gene circuit design in synthetic biology.

Efficient adsorption of tetracycline in aquatic system by thermally-treated sediment.

The disposal of dredged sediment is a considerable challenge for environmental protection and resource utilization. In this study, the dredged sediment was thermally-treated to prepare as adsorbent and utilized for tetracycline adsorption. Sediments based adsorbents under different pyrolysis temperature and atmosphere (N2 and limited oxygen) were obtained and 600 °C and N2 atmosphere (600AN) exhibited maximum TC adsorption capacity (15.45 mg/g). SEM, N2 adsorption-desorption isotherm, XRD, FTIR and XPS analysis suggested larger pore volume, relatively higher surface area, effective pore size distribution and abundant surface functional groups were the main reasons. Moreover, the influence of key adsorption parameters, including adsorbent dosage, initial pH, coexisting ions, ionic strength, contact time, initial TC concentration and ambient temperature had also been investigated. Results revealed that TC adsorption by 600AN were more consistent with pseudo-second order kinetic and Freundlich isothermal models. Combined with characterization results, which reasonably inferred that the adsorption mechanisms of 600AN were mainly involved pore-filling effect, hydrogen bonding interaction and π-π EDA interaction. This work has provided a low-cost, high efficiency and promising method for the dredged sediment reduction and resource recovery.

Efficacy and safety of autologous adipose tissue-derived stromal vascular fraction in patients with thin endometrium: a protocol for a single-centre, longitudinal, prospective self-control study.

INTRODUCTION: Endometrial thickness is an important parameter to evaluate endometrial receptivity. An appropriate endometrial thickness is necessary for both embryo implantation and maintaining normal pregnancy. Women with thin endometrium are one of the critical challenges in the clinic, and current therapeutic strategies for thin endometrium remain suboptimal. The stromal vascular fraction (SVF) derived from adipose tissue contains a variety of cells, mainly adipose-derived stem/stromal cells and adipose cells. Recently, adipose tissue-derived SVF showed tremendous potential for treating thin endometrium due to its capacity to repair and regenerate tissues. The application of SVF in animal models for treating thin endometrium has been investigated. However, limited evidence has demonstrated the efficacy and safety of autologous SVF in patients with thin endometrium. METHODS AND ANALYSIS: This study is a single-centre, longitudinal, prospective self-control study to investigate the preliminary efficacy and safety of autologous SVF in improving the pregnancy outcome of infertile patients with thin endometrium. Thirty patients diagnosed with thin endometrium will be recruited based on the inclusion and exclusion criteria. The SVF suspension will be transferred into the uterine cavity via an embryo transfer catheter. Then, comparisons between pretreatment and post-treatment will be analysed, and the outcomes, including endometrial thickness, menstrual volume and duration, frequency and severity of adverse events and early pregnancy outcomes, will be measured within a 3-month follow-up, while late pregnancy outcomes and their offspring will be followed up via telephone for 2 years. The proportion of patients with improved symptoms will be calculated and compared. ETHICS AND DISSEMINATION: This study was approved by the Ethics Committee of Peking University Third Hospital (reference number: REC2020-165). Written informed consent will be provided for patients before being included. The results will be presented at academic conferences and a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ChiCTR2000035126.

Mendelian randomization analyses support causal relationships between blood metabolites and the gut microbiome.

The gut microbiome has been implicated in a variety of physiological states, but controversy over causality remains unresolved. Here, we performed bidirectional Mendelian randomization analyses on 3,432 Chinese individuals with whole-genome, whole-metagenome, anthropometric and blood metabolic trait data. We identified 58 causal relationships between the gut microbiome and blood metabolites, and replicated 43 of them. Increased relative abundances of fecal Oscillibacter and Alistipes were causally linked to decreased triglyceride concentration. Conversely, blood metabolites such as glutamic acid appeared to decrease fecal Oxalobacter, and members of Proteobacteria were influenced by metabolites such as 5-methyltetrahydrofolic acid, alanine, glutamate and selenium. Two-sample Mendelian randomization with data from Biobank Japan partly corroborated results with triglyceride and with uric acid, and also provided causal support for published fecal bacterial markers for cancer and cardiovascular diseases. This study illustrates the value of human genetic information to help prioritize gut microbial features for mechanistic and clinical studies.

Identification of two downregulated circRNAs in patients with acute B-lymphocytic leukemia.

Acute B-lymphocytic leukemia (B-ALL) is associated with a high mortality rate, with no effective treatment strategies available. The identification of diagnostic and prognostic biomarkers of B-ALL can contribute to the development of novel therapeutic methods and drugs, which can improve the survival outcomes of patients with B-ALL. The present study aimed to identify downregulated circular RNAs (circRNAs) in patients with B-ALL. RNA sequencing was performed to construct the circRNA expression profiles in B-ALL cells and normal human lymphoblasts. The Database for Annotation, Visualization and Integrated Discovery was used to perform Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses. In addition, reverse transcription-quantitative (RT-q)PCR analysis was performed to detect the expression levels of the downregulated circRNAs. A total of 263 differentially expressed circRNAs were identified, including 76 upregulated and 187 downregulated circRNAs, respectively. The upregulated circRNAs were mainly enriched in 'macromolecule modification', 'protein modification' and 'cellular protein modification processes', while the downregulated circRNAs were mainly enriched in the 'negative regulation of RNA biosynthetic processes', 'natural killer cell-mediated cytotoxicity' and 'viral carcinogenesis'. RT-qPCR analysis demonstrated that two of the downregulated circRNAs (hsa_circ_0000745 and chr15:87949594-87966067-), identified during microarray analysis were also significantly downregulated in Ball-1 cells and B-ALL bone marrow samples. Thus, these circRNAs may serve as biomarkers for patients with B-ALL.

Over 50,000 Metagenomically Assembled Draft Genomes for the Human Oral Microbiome Reveal New Taxa.

The oral cavity of each person is home to hundreds of bacterial species. While taxa for oral diseases have been studied using culture-based characterization as well as amplicon sequencing, metagenomic and genomic information remains scarce compared to the fecal microbiome. Here, using metagenomic shotgun data for 3346 oral metagenomic samples together with 808 published samples, we obtain 56,213 metagenome-assembled genomes (MAGs), and more than 64% of the 3589 species-level genome bins (SGBs) contain no publicly available genomes. The resulting genome collection is representative of samples around the world and contains many genomes from candidate phyla radiation (CPR) that lack monoculture. Also, it enables the discovery of new taxa such as a genus Candidatus Bgiplasma within the family Acholeplasmataceae. Large-scale metagenomic data from massive samples also allow the assembly of strains from important oral taxa such as Porphyromonas and Neisseria. The oral microbes encode genes that could potentially metabolize drugs. Apart from these findings, a strongly male-enriched Campylobacter species was identified. Oral samples would be more user-friendly collected than fecal samples and have the potential for disease diagnosis. Thus, these data lay down a genomic framework for future inquiries of the human oral microbiome.

Life History Recorded in the Vagino-cervical Microbiome Along with Multi-omes.

The vagina contains at least a billion microbial cells, dominated by lactobacilli. Here we perform metagenomic shotgun sequencing on cervical and fecal samples from a cohort of 516 Chinese women of reproductive age, as well as cervical, fecal, and salivary samples from a second cohort of 632 women. Factors such as pregnancyhistory, delivery history, cesarean section, and breastfeeding were all more important than menstrual cycle in shaping the microbiome, and such information would be necessary before trying to interpret differences between vagino-cervical microbiome data. Greater proportion of Bifidobacterium breve was seen with older age at sexual debut. The relative abundance of lactobacilli especially Lactobacillus crispatus was negatively associated with pregnancy history. Potential markers for lack of menstrual regularity, heavy flow, dysmenorrhea, and contraceptives were also identified. Lactobacilli were rare during breastfeeding or post-menopause. Other features such as mood fluctuations and facial speckles could potentially be predicted from the vagino-cervical microbiome. Gut and salivary microbiomes, plasma vitamins, metals, amino acids, and hormones showed associations with the vagino-cervical microbiome. Our results offer an unprecedented glimpse into the microbiota of the female reproductive tract and call for international collaborations to better understand its long-term health impact other than in the settings of infection or pre-term birth.

Metagenome-genome-wide association studies reveal human genetic impact on the oral microbiome.

The oral microbiota contains billions of microbial cells, which could contribute to diseases in many body sites. Challenged by eating, drinking, and dental hygiene on a daily basis, the oral microbiota is regarded as highly dynamic. Here, we report significant human genomic associations with the oral metagenome from more than 1915 individuals, for both the tongue dorsum (n = 2017) and saliva (n = 1915). We identified five genetic loci associated with oral microbiota at study-wide significance (p < 3.16 × 10-11). Four of the five associations were well replicated in an independent cohort of 1439 individuals: rs1196764 at APPL2 with Prevotella jejuni, Oribacterium uSGB 3339 and Solobacterium uSGB 315; rs3775944 at the serum uric acid transporter SLC2A9 with Oribacterium uSGB 1215, Oribacterium uSGB 489 and Lachnoanaerobaculum umeaense; rs4911713 near OR11H1 with species F0422 uSGB 392; and rs36186689 at LOC105371703 with Eggerthia. Further analyses confirmed 84% (386/455 for tongue dorsum) and 85% (391/466 for saliva) of host genome-microbiome associations including six genome-wide significant associations mutually validated between the two niches. As many of the oral microbiome-associated genetic variants lie near miRNA genes, we tentatively validated the potential of host miRNAs to modulate the growth of specific oral bacteria. Human genetics accounted for at least 10% of oral microbiome compositions between individuals. Machine learning models showed that polygenetic risk scores dominated over oral microbiome in predicting risk of dental diseases such as dental calculus and gingival bleeding. These findings indicate that human genetic differences are one explanation for a stable or recurrent oral microbiome in each individual.

The gelling behavior of gellan in the presence of different sodium salts.

It is well known that metal ions have great effects on gelling behaviors of gellan aqueous systems, however, the effects of their co-ions - anions have rarely been studied. Herein, we investigated the effects of four kinds of sodium salts with different anions (NaCl, CH3COONa, Na2C2O4 and Na3C6H5O7) on gelling behaviors of gellan aqueous systems in terms of gelling temperature and gel hardness. It was found that, when [Na+] was low (20 mM), the salt with Cl- or CH3COO- favored the gelling of gellan aqueous systems, while the salt with C2O42- or C6H5O73- took adverse effects probably because C2O42- or C6H5O73- could react with divalent cations (Ca2+ and Mg2+) in gellan to form precipitates or chelates and break their interactions with gellan (salt bridges). When [Na+] was high (50 or 80 mM), all the four kinds of salts facilitated gelling due to the shielding effects of high concentrations of Na+ on the negative charges along the gellan chains, and followed the order of: Cl- > CH3COO- > C2O42- > C6H5O73-. This study demonstrates the effects of anion kind of salts on gelling behaviors of gellan aqueous systems and provides references for the application of gellan.

Cervicovaginal microbiome dynamics after taking oral probiotics.

The vaginal microbiota is less complex than the gut microbiota, and the colonization of Lactobacillus in the female vagina is considered to be critical for reproductive health. Oral probiotics have been suggested as promising means to modulate vaginal homeostasis in the general population. In this study, 60 Chinese women were followed for over a year before, during, and after treatment with the probiotics Lactobacillus rhamnosus GR-1 and Lactobacillusreuteri RC-14. Shotgun metagenomic data of 1334 samples from multiple body sites did not support a colonization route of the probiotics from the oral cavity to the intestinal tract and then to the vagina. Our analyses enable the classification of the cervicovaginal microbiome into a stable state and a state of dysbiosis. The microbiome in the stable group steadily maintained a relatively high abundance of Lactobacilli over one year, which was not affected by probiotic intake, whereas in the dysbiosis group, the microbiota was more diverse and changed markedly over time. Data from a subset of the dysbiosis group suggests this subgroup possibly benefited from supplementation with the probiotics, indicating that probiotics supplementation can be prescribed for women in a subclinical microbiome setting of dysbiosis, providing opportunities for targeted and personalized microbiome reconstitution.

Preparation, characterization and primary evaluation of trilayered biliary stent films for anti-cholangiocarcinoma and anti-biofilm formation.

Excessive growth of tumor within biliary wall and formation of biofilm on inner surface of stent can cause restenosis or even obstruction after stent implantation. Therefore, it is important and valuable to develop a new biliary stent for anti-cholangiocarcinoma and anti-biofilm formation. Herein, we designed, prepared and primarily evaluated a new trilayered film for biliary stents consisting of one poly (lactic acid) (PLA) layer loaded with anti-tumor paclitaxel (PTX layer), one middle PLA isolation layer (isolation layer) and one PLA layer loaded with antimicrobial ofloxacin (OFLX layer). It is postulated that the PTX layer releases drug towards biliary wall with tumor, the OFLX layer releases drug towards lumen of bile duct and the isolation layer is used to separate from the PTX layer and the OFLX layer and facilitate drug release in unidirectional way. The prepared trilayered films were characterized in terms of morphology, microstructure, crystallinity and biodegradability. It was found that the films could effectively tune drug release by addition of different amounts of drug or PEG, release PTX and OFLX in opposite directions, effectively inhibit the proliferation of human cholangiocarcinoma RBE cells, the adherence of E. coli and S. aureus and the formation of biofilm in vitro. It is potential that the trilayered films can be used to fabricate a new biliary stent with a dual function of anti-cholangiocarcinoma and anti-biofilm formation.

Mutant Zp1 impedes incorporation of ZP3 and ZP4 in the zona pellucida, resulting in zona absence and female infertility in rats†.

The zona pellucida (ZP) plays vital roles in reproductive processes including oogenesis, fertilization, and preimplantation development. Both human and rat ZP consist of four glycoproteins, called ZP1, ZP2, ZP3, and ZP4. Our previous research reported a novel Zp1 mutation in cases of human infertility, associated with an abnormal phenotype involving the absence of the ZP. Here, we developed a homologous rat strain to investigate the pathogenic effect. The ovaries of homozygous (Zp1MT/MT) females possessed both growing and fully grown oocytes; the oocytes completely lacked a ZP, but ZP1 was detectable inside the cytoplasm. Only 1-2 eggs were recovered from oviducts of superovulated Zp1MT/MT females, while an average of 21 eggs were recovered from superovulated Zp1WT/WT per female. The eggs of Zp1MT/MT females were not surrounded by a ZP and lost their fertilization capacity in vitro. Zp1MT/MT females mated with wild-type males failed to become pregnant. Studies in 293T cells showed that mutant Zp1 resulted in a truncated ZP1 protein, which might be intracellularly sequestered and interacted with wild-type ZP3 or ZP4. Our results suggest that the Zp1 point mutation led to infertility and loss of the ZP in oocytes in rats.

Clinical Significance of ZNF711 in Human Breast Cancer.

PURPOSE: To investigate the clinicopathologic and prognostic significance of the zinc-finger protein 711 (ZNF711) in breast cancer (BCa). MATERIALS AND METHODS: The relevance of ZNF711 in BCa was analyzed using bioinformatics. The expression of ZNF711 was detected by immunohistochemistry in paraffin blocks of BCa. To evaluate its clinical significance, the correlation between the expression of ZNF711 and BCa clinical indicators, including estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER-2), was analyzed. Finally, the Kaplan-Meier method was applied to explore the prognostic value of ZNF711. RESULTS: ZNF711 expression was decreased in BCa and was negatively correlated with ER expression (P < 0.05) and positively correlated with HER-2 expression (P < 0.01), but there was no significant correlation between ZNF711 and PR expression. ZNF711 expression was not correlated with age, tumor diameter, or lymph node metastasis; however, ZNF711 expression was correlated with staging in BCa. Survival analysis results showed that the ZNF711-positive group patients had a poorer prognosis compared with the ZNF711-negative group. CONCLUSION: The expression of ZNF711 was deceased in BCa and closely related to ER and HER-2 expression. Therefore, ZNF711 could not only serve as a predictor of BCa with poor prognosis but also as a potential biomarker for targeted therapy.