Boosting the Downconversion Luminescence of Tm3+-Doped Nanoparticles for S-Band Polymer Waveguide Amplifier.

Polymer waveguide devices have attracted increasing interest in several rapidly developing areas of broadband communications since they are easily adaptable to on-chip integration and promise low propagation losses. As a key member of the waveguide gain medium, lanthanide doped nanoparticles have been intensively studied to improve the downconversion luminescence. However, current research efforts are almost confined to erbium-doped nanoparticles and amplifiers operating at the C-band; boosting the downconversion luminescence of Tm3+ for S-band optical amplification still remains a challenge. Here we report a Tb3+-induced deactivation control to enhance Tm3+ downconversion luminescence in a stoichiometric Yb lattice without suffering from concentration quenching. We also demonstrate their potential application in an S-band waveguide amplifier and record a maximum optical gain of 18 dB at 1464 nm. Our findings provide valuable insights into the fundamental understanding of deactivation-controlled luminescence enhancement and open up a new avenue toward the development of an S-band polymer waveguide amplifier with high gain.

An Ultra-low Detection Limit Fe3+ Optical Fiber Fluorescent Sensor Based on a Anti-B18H22 Derivative with Aggregation-induced Emission Enhancement.

A fluorescent Fe3+ probe ((C10H7NO2)2B18H20, M1) by introducing two isoquinoline-1-carboxylic acid group into the 6,9-position of anti-B18H22 was designed and synthesized. The structure of M1 was investigated by 1H NMR, MS, FT-IR and theoretical calculation, and its optical properties were characterized with UV-Vis and PL. M1 showed aggregation induced emission enhancement (AIEE) properties in THF/H2O solution, and exhibited an excellent selectivity toward Fe3+ in THF/H2O (v/v, ƒw = 95%) solution with a detection limit of 1.93 × 10-5 M. The interaction mechanism of probe for detecting Fe3+ is attributed to the involvement of intramolecular charge transfer (ICT) process. Furthermore, a optical fiber fluorescent Fe3+ sensor based on M1 sensing film was developed, the detection limit of the optical fiber Fe3+ fluorescent sensor could be improved to13.8 pM, the ultra-low detection limit is superior to most reported fluorescent probes (or sensors) towards Fe3+. This method has the advantages of high sensitivity, anti-interference and easy to operate, and has great potential in the field of the analysis of environmental and biological samples.

A qualitative study on patients' and health care professionals' perspectives regarding care delivered during CIED operation.

BACKGROUND: Cardiac implantable electronic devices (CIEDs) has proven to be an invaluable tool in the practice of cardiology. Patients who have undergone CIED surgery with local anesthesia may result in fear, insecurity and suffering. Some studies have put efforts on ways to improve intraoperative experience of patients with local anesthesia, but researches concerning experiences of CIED patients during surgery is in its infancy. METHODS: Based on semi-structured and in-depth interviews, a qualitative design was conducted in a tertiary general hospital in China from May 2022 to July 2023.Purposeful sampling of 17 patients received CIED surgery and 20 medical staff were interviewed. Thematic analysis with an inductive approach was used to identify dominant themes. RESULTS: Four themes emerged from the data: (1) Safety and success is priority; (2) Humanistic Caring is a must yet be lacking; (3) Paradox of surgery information given; (4) Ways to improve surgery experiences in the operation. CONCLUSIONS: Intraoperative care is significant for CIED surgery. To improve care experience during surgery, healthcare professionals should pay attention to patients' safety and the factors that affecting humanistic caring in clinical practice. In addition, information support should consider information-seeking styles and personal needs. Besides, the four approaches presented in this study are effective to improve the intraoperative care experience.

Highly applicable dual-cathode electro-Fenton system with self-adjusting pH and ferrous species.

Due to the high dependence on the pH of influent water and the level of ferrous species, the applicability of the electro-Fenton (EF) system is poor. A highly applicable dual-cathode (DC) EF system with self-adjusting pH and ferrous species is proposed: gas diffusion electrode (GDE) for generation H2O2 and Fe/S doped multi-walled carbon nanotubes (Fe/S-MWCNT) modification active cathode (AC) for adjusting pH and iron species. The strong synergistic enhancement effect between two cathodes (synergy factor up to 90.3%) improves the catalytic activity of this composite system about 12.4 times higher than that of cathode alone. Impressively, AC has the ability of self-regulate to shift towards the optimal Fenton pH (around 3.0) without adding reagents. Even pH can be adjusted from 9.0 to 3.4 within 60 min. This characteristic gives the system a wide range of pH applications, while avoiding the disadvantage of the high cost of traditional EF in pre-acidification. Furthermore, DC has a high and stable ferrous species supply, and the iron leaching amount is about twice less than that of heterogeneous EF system. Long-term stability of the DC system and its easy activity regeneration exhibit the potential of environmental remediation in industrial application.

Investigating the electrochemical advanced oxidation mechanism of N-doped graphene aerogel: Molecular dynamics simulation combined with DFT method.

Nitrogen-doped graphene as a perfectly-efficient and environmentally compatible electrocatalyst won widespread attention in electrochemical advanced oxidation processes (EAOP). However, the relationship between surface structure regulation and activity of catalysts is still lacking in systematic scientific guidance. Herein, nitrogen-doped graphene aerogel (NGA) was conveniently prepared through hydrothermal treatment, and then utilized to fabricate the gas diffusion electrode (GDE) as the cathode for tetracycline (TC) removal. High free radical yield (81.2 µM) and fast reaction rate (0.1469 min-1) were found in NGA system. The molecular dynamics simulation (MD) results showed that the interaction energy of NGA was greater than the raw graphene aerogel (GA). The adsorption activation of H2O2 and the degradation of TC occurred in the first adsorption layer of catalysts, and both processes turned more orderly after nitrogen doping. Moreover, the van der Waals interaction was stronger than the electrostatic interaction. Density function theory (DFT) revealed that the adsorption energy of H2O2 at graphitic N, pyridinic N, and pyrrolic N sites was -0.03 eV, -0.39 eV, and -0.30 eV, respectively. Pyridinic N sites were inferred as the main functional regions of in-situ activation •OH, there were more likely to occur ectopic reaction in pyrrolic N, and graphitic N were responsible for improving H2O2 production. By revealing the microstructure and activation characteristics of NGA, an experiment-simulation complementary strategy is provided in the EAOP to discover or to optimize new catalysts.

Multifunctional Novel Nanoplatform for Effective Synergistic Chemo-Photodynamic Therapy of Breast Cancer by Enhancing DNA Damage and Disruptions of Its Reparation.

Photodynamic therapy (PDT) is an effective noninvasive therapeutic strategy that has been widely used for anti-tumor therapy by the generation of excessive highly cytotoxic ROS. However, the poor water solubility of the photosensitizer, reactive oxygen species (ROS) depleting by high concentrations of glutathione (GSH) in the tumor microenvironment and the activation of DNA repair pathways to combat the oxidative damage, will significantly limit the therapeutic effect of PDT. Herein, we developed a photosensitizer prodrug (CSP) by conjugating the photosensitizer pyropheophorbide a (PPa) and the DNA-damaging agent Chlorambucil (Cb) with a GSH-responsive disulfide linkage and demonstrated a multifunctional co-delivery nanoplatform (CSP/Ola nanoparticles (NPs)) together with DSPE-PEG2000 and PARP inhibitor Olaparib (Ola). The CSP/Ola NPs features excellent physiological stability, efficient loading capacity, much better cellular uptake behavior and photodynamic performance. Specifically, the nanoplatform could induce elevated intracellular ROS levels upon the in situ generation of ROS during PDT, and decrease ROS consumption by reducing intracellular GSH level. Moreover, the CSP/Ola NPs could amplify DNA damage by released Cb and inhibit the activation of Poly(ADP-ribose) polymerase (PARP), promote the upregulation of γ-H2AX, thereby blocking the DNA repair pathway to sensitize tumor cells for PDT. In vitro investigations revealed that CSP/Ola NPs showed excellent phototoxicity and the IC50 values of CSP/Ola NPs against MDA-MB-231 breast cancer cells were as low as 0.05-01 µM after PDT. As a consequence, the co-delivery nanoplatform greatly promotes the tumor cell apoptosis and shows a high antitumor performance with combinational chemotherapy and PDT. Overall, this work provides a potential alternative to improve the therapeutic efficiency of triple negative breast cancer cell (TNBC) treatment by synergistically enhancing DNA damage and disrupting DNA damage repair.

Preparation of novel HKUST-1-glucose oxidase composites and their application in biosensing.

Copper-based metal-organic frameworks (MOF) and multi-walled carbon nanotubes (HKUST-1-MWCNTs) composite were synthesized by one-step hydrothermal method, and PDA-enzyme-HKUST-1-MWCNTs composite was prepared by one-pot method for the construction of glucose biosensors, which realized the sensitive amperometric detection of glucose at 0.7 V (vs. SCE). The sensitivity of the sensor for glucose detection was 178 µA mM-1cm-2 in the wide linear range of 0.005 ~ 7.05 mM, the detection limit was 0.12 µM and the corresponding RSD was 3.8%. Its high performance is mainly benefitted from the high porosity and large specific surface area of HKUST-1, the good conductivity of MWCNTs, and the excellent adhesion and dispersion of PDA. The strategy of combining PDA and MWCNTs to improve the dispersion and conductivity of MOF is expected to achieve a wider application of MOF-based materials in the electrochemical biosensing field.

A synthetic health risk assessment based on geochemical equilibrium simulation and grid spatial interpolation for zinc (II) species.

Soil heavy metal pollution has become a global issue involving environmental safety and human health risks. This paper quantified the sources of heavy metals by positive matrix factorization (PMF) model and explored the spatial distribution of heavy metals by means of grid scales, with an industrial site as the study area in Suzhou. The PMF identified four pollution sources of heavy metal in soil, and the quantitative results revealed that industrial activities (33.5%) contributed the most to heavy metals, followed by soil parent materials (30.8%) and agricultural activities (19.7%). Zinc (Zn) was screened out as the targeted metal (TM) through the potential ecological risk assessment, the metal species of which was simulated by the geochemical software PHREEQC. This research aimed to determine the dominant metal species of TM with high-risk levels to realize the transformation of toxic metal species. Herein, according to the morphological evolution of metal species, the activity and concentration of the Zn ion species were obtained for both carcinogenic and non-carcinogenic risk assessment. The evaluation of the optimized human health risk demonstrated that the associated health risk of Zn (II) ions depended predominantly on its metal speciation. Overall, the optimized carcinogenic and non-carcinogenic risk value of Zn2S32- for adults was 2.01E-04 and for children was 1.31, resulting in corresponding hazardous risk to humans, which accounted for high-risk levels of 61.5% and 58.5% for adults and children, respectively. The OHRA method can provide a reference for the decision-making of soil heavy metal pollution and remediation for specific heavy metals in polluted areas.

Periodontal ligament cells derived small extracellular vesicles are involved in orthodontic tooth movement.

OBJECTIVES: Small extracellular vesicles (EVs) from human periodontal ligament cells (hPDLCs) are closely associated with periodontal homeostasis. Far less is known about EVs association with orthodontic tooth movement (OTM). This study aimed to explore the role of small EVs originated from hPDLCs during OTM. MATERIALS AND METHODS: Adult C57BL/6 mice were used. Springs were bonded to the upper first molars of mice for 7 days to induce OTM in vivo. To block small EVs release, GW4869 was intraperitoneally injected and the efficacy of small EVs inhibition in periodontal ligament was verified by transmission electron microscope (TEM). Tooth movement distance and osteoclastic activity were studied. In vitro, hPDLCs were isolated and administered compressive force in the EV-free culture media. The cell morphologies and CD63 expression of hPDLCs were studied. Small EVs were purified and characterized using a scanning electron microscope, TEM, western blot, and nanoparticle tracking analysis. The expression of proteins in the small EVs was further processed and validated using a human immuno-regulated cytokines array and an enzyme-linked immunosorbent assay (ELISA). RESULTS: The small EV depletion significantly decreased the distance and osteoclastic activity of OTM in the mice. The hPDLCs displayed different morphologies under force compression and CD63 expression level decreased verified by western blot and immunofluorescence staining. Small EVs purified from supernatants of the hPDLCs showed features with <200 nm diameter, the positive EVs marker CD63, and the negative Golgi body marker GM130. The number of small EVs particles increased in hPDLCs suffering force stimuli. According to the proteome array, the level of soluble intercellular adhesion molecule-1 (sICAM-1) displayed the most significant fold change in small EVs under compressive force and this was further confirmed using an ELISA. LIMITATIONS: Further mechanism studies are warranted to validate the hPDLC-originated small EVs function in OTM through proteins delivery. CONCLUSIONS: The notable decrease in the OTM distance after small EV blocking and the significant alteration of the sICAM-1 level in the hPDLC-originated small EVs under compression provide a new vista into small EV-related OTM biology.

The SR-protein FgSrp2 regulates vegetative growth, sexual reproduction and pre-mRNA processing by interacting with FgSrp1 in Fusarium graminearum.

Serine/arginine (SR) proteins play significant roles in pre-mRNA splicing in eukaryotes. To investigate how gene expression influences fungal development and pathogenicity in Fusarium graminearum, a causal agent of Fusarium head blight (FHB) of wheat and barley, our previous study identified a SR protein FgSrp1 in F. graminearum, and showed that it is important for conidiation, plant infection and pre-mRNA processing. In this study, we identified another SR protein FgSrp2 in F. graminearum, which is orthologous to Schizosaccharomyces pombe Srp2. Our data showed that, whereas yeast Srp2 is essential for growth, deletion of FgSRP2 resulted in only slight defects in vegetative growth and perithecia melanization. FgSrp2 localized to the nucleus and both its N- and C-terminal regions were important for the localization to the nucleus. FgSrp2 interacted with FgSrp1 to form a complex in vivo. Double deletion of FgSRP1 and FgSRP2 revealed that they had overlapping functions in vegetative growth and sexual reproduction. RNA-seq analysis revealed that, although deletion of FgSRP2 alone had minimal effects, deletion of both FgSRP1 and FgSRP2 caused significant changes in gene transcription and RNA splicing. Overall, our results indicated that FgSrp2 regulates vegetative growth, sexual reproduction and pre-mRNA processing by interacting with FgSrp1.

The tri-snRNP specific protein FgSnu66 is functionally related to FgPrp4 kinase in Fusarium graminearum.

Deletion of Prp4, the only kinase among spliceosome components, is not lethal in Fusarium graminearum but Fgprp4 mutants have severe growth defects and produced spontaneous suppressors. To identify novel suppressor mutations of Fgprp4, we sequenced the genome of suppressor S37 that was normal in growth but only partially recovered for intron splicing and identified a tandem duplication of 9-aa in the tri-snRNP component FgSNU66. Among the 19 additional suppressor strains found to have mutations in FgSNU66 (out of 260 screened), five had the same 9-aa duplication event with S37 and another five had the R477H/C mutation. The rest had nonsense or G-to-D mutations in the C-terminal 27-aa (CT27) region of FgSnu66, which is absent in its yeast ortholog. Truncation of this C-terminal region reduced the interaction of FgSnu66 with FgHub1 but increased its interaction with FgPrp8 and FgPrp6. Five phosphorylation sites were identified in FgSnu66 by phosphoproteomic analysis and the T418A-S420A-S422A mutation was shown to reduce virulence. Overall, our results showed that mutations in FgSNU66 can suppress deletion of Fgprp4, which has not been reported in other organisms, and the C-terminal tail of FgSnu66 plays a role in its interaction with key tri-snRNP components during spliceosome activation.

Predicting future contents of soil heavy metals and related health risks by combining the models of source apportionment, soil metal accumulation and industrial economic theory.

Enriched and bio-refractory soil heavy metals (SHMs) originate from the underground mineral, which supplies energy and materials for the development of economy and industry. Investigating soil metal contents and their adverse health impacts is the principal concern associated metal contaminated industrial areas, including both current assessments and future projections. In this research, we create a novel spatiotemporal model of SHMs prediction and risk characterization for future by citing a rigorous theory of industrial economics, and time series of activity intensity changes of various pollution sources are forecasted. The dynamic change of source contributions is quantitatively resolved and the mean SHMs concentrations are estimated by classical formulas for heavy metal accumulation. Human health risk in the future is described in a manner of time series. The results of the case study show that contribution rates of the five sources of the six metals change continuously over time. Pb, Cd and As assume the highest growth rates (400%, 500% and 165%), while Zn, Ni, Cr possesses relatively lower growth (< 130%), compared to their corresponding background values. Health risk of local sensitive population (children) is estimated at exceeding threshold in 2022 (non-carcinogenic) and 2012 (carcinogenic), and the upward trend will continue. Traffic emission, agriculture and household garbage are identified as major risky sources in the coming decades at the studied area, and improvement measures are recommended. Although a degree of uncertainties exists, the overall tendency is a conservative bias for chemical risk. Additionally, this paper is the first to explore a methodology of predicting future SHMs and associated human health risk, based on industrial economics and temporal source apportionment.

Implementation of long-term assessment of human health risk for metal contaminated groundwater: A coupled chemical mass balance and hydrodynamics model.

Assessing human health risk using spatiotemporal migration and geochemical evolution concurrently in an area where the groundwater is contaminated with heavy metals can provide more instructive information to protect specific potential negative impacts on human health. In this research, we established a model of long-term assessment of human health risk for metal contaminated groundwater by coupling two models: the geochemical (based on the law of chemical mass balance) model and the hydrodynamics module. The hydrodynamics module is used to initially identify the total temporal concentration of various elements, and the chemical mass balance module is used to gain the concentration and ionic activity of various toxic elements according to the range of environmental pH. Effective concentrations calculated using activity weight (based on speciation and ionic activity) were introduced into the formula for risk analysis. The results of the study show that, with the exploitation and recharge of groundwater, the non-carcinogenic and carcinogenic health risks cannot be reduced to acceptable levels until 18 and 22 years, respectively. The calculated risk values of using the coupling model are lower than that of statistics or single hydrokinetics. The sensitivity analysis results show that this model is reliable. The recharge, pH and the permeability coefficient are defined as the most sensitive factors.

Pelagivirga sediminicola gen. nov., sp. nov. isolated from the Bohai Sea.

A Gram-stain-negative bacterium, strain BH-SD19T, that was isolated from a marine sediment sample collected from the Bohai Sea, was subjected to a polyphasic taxonomic study. Cells of BH-SD19T are non-flagellated, non-gliding, oval-shaped rods, 0.5-1.0 µm wide and 1.0-2.0 µm long. BH-SD19T is strictly aerobic, and oxidase- and catalase-positive. Growth occurs at 15-40 °C (optimum 35 °C), at pH 6.0-8.5 (optimum 7.0-7.5) and with 1-10 % (w/v) NaCl (optimum 2 %). The predominant fatty acids are C19 : 0cyclo ω8c (46.5 %), C16 : 0 (20.3 %) and C18 : 1ω7c and/or C18 : 1ω6c (10.6 %). The major respiratory quinone is Q-10. The major polar lipids are phosphatidylglycerol, phosphatidylethanolamine and an unidentified phospholipid. The DNA G+C content is 64.0 mol%. BH-SD19T shows the highest 16S rRNA sequence similarity to Pontibaca methylaminivorans (95.2 %) and strains of species of the genus Roseovarius(93.4-95.2 %). Sequence similarity values between BH-SD19T and other phylogenetically related species are all below 95.0 %. Phylogenetic trees based on 16S rRNA gene sequences indicate that BH-SD19T forms a distinct lineage and does not join any known genera in the trees. Phenotypic, chemotaxonomic and phylogenetic data indicate that BH-SD19T represents a novel genus and species in the family Rhodobacteraceae, for which the name Pelagivirga sediminicola gen. nov., sp. nov. is proposed. The type strain is BH-SD19T (=CCTCC AB 2017074T=KCTC 62202T).

Establishing a health risk assessment for metal speciation in soil-A case study in an industrial area in China.

An improved method was proposed which integrates the distribution of metal speciation simulated by chemical equilibrium model, different exposure models and average daily intake dose modified by analytic hierarchy process for human health risk assessment of metal species (MS). With the rapid development of economic and urbanization, the metals pollution had become more serious in industrial areas. Adverse effects of soil contaminants on human health in typical industrial area should be assessed to evaluate the risks of soils in these areas. The method was applied to study nickel (Ni) species health risks in soil of industrial areas. The pH possessed significant impact to determine distribution/existence and solubility of Ni species, followed by DOC. The non-carcinogenic risk (HQ) of Ni species were less than 1 in each sampling points, except Ni2+. In addition, the carcinogenic risk (CR) of different Ni species were less than 10-6, except for FANi and Ni2+.

The FgSRP1 SR-protein gene is important for plant infection and pre-mRNA processing in Fusarium graminearum.

The versatile functions of SR (serine/arginine-rich) proteins in pre-mRNA splicing and processing are modulated by reversible phosphorylation. Previous studies showed that FgPrp4, the only protein kinase among spliceosome components, is important for intron splicing and the FgSrp1 SR protein is phosphorylated at five conserved sites in Fusarium graminearum. In this study, we showed that the Fgsrp1 deletion mutant rarely produced conidia and caused only limited symptoms on wheat heads and corn silks. Deletion of FgSRP1 also reduced ascospore ejection and deoxynivalenol (DON) production. Interestingly, FgSRP1 had two transcript isoforms due to alternative splicing and both of them were required for its normal functions in growth and DON biosynthesis. FgSrp1 localized to the nucleus and interacted with FgPrp4 in vivo. Deletion of all four conserved phosphorylation sites but not individual ones affected the FgSRP1 function, suggesting their overlapping functions. RNA-seq analysis showed that the expression of over thousands of genes and splicing efficiency in over 140 introns were affected. Taken together, FgSRP1 is important for conidiation, and pathogenesis and alternative splicing is important for its normal functions. The FgSrp1 SR protein is likely important for pre-mRNA processing or splicing of various genes in different developmental and infection processes.

Expression and Correlation of Hypoxia-Inducible Factor-1α (HIF-1α) with Pulmonary Artery Remodeling and Right Ventricular Hypertrophy in Experimental Pulmonary Embolism.

BACKGROUND We investigated the expression of HIF-1α (hypoxia-inducible factor-1α) and its correlations with pulmonary artery remodeling and right ventricular hypertrophy in PE (pulmonary embolism) rats. MATERIAL AND METHODS After the PE rat model was established, the dynamic changes of mPAP (mean pulmonary artery pressure), PAMT (relative medial thickness of small pulmonary arteries), WA/TA (vessel wall area/total area), and RVHI (right ventricular hypertrophy index) were detected. Then, histomorphology of pulmonary vascular was observed, followed by HIF-1α mRNA and protein for pulmonary artery and right ventricle were checked via in situ hybridization and immunohistochemistry, respectively. The correlations between HIF-1α and mPAP, PAMT, WA/TA, and RVHI were analyzed. RESULTS The mPAP level increased from the initial time to 12 weeks of PE and reached the peak at 12 weeks. After 4 weeks of PE, PAMT increased compared with the initial control group (p<0.05), and increased further after 8 weeks and 12 weeks. Changes of the vessel WA/TA were the same as PAMT. Compared with the initial control group, RVHI increased at 8 weeks (p<0.05) and 12 weeks of PE (p<0.01). HIF-1α mRNA and protein were positively correlated with mPAP, PAMT, and WA/TA in pulmonary arteries. HIF-1α mRNA and protein were positively correlated with mPAP, PAMT, WA/TA, and RVHI in right ventricles (p<0.01). CONCLUSIONS HIF-1α mRNA and protein are expressed in the pulmonary artery and right ventricular of PE rats, and HIF-1α may correlate with pulmonary artery remodeling and right ventricular hypertrophy in rats with PE.

miR-99a suppresses the metastasis of human non-small cell lung cancer cells by targeting AKT1 signaling pathway.

MicroRNAs (miRNAs) play an important role in the development and progression of non-small cell lung cancer (NSCLC). Recently, several studies have shown that miR-99a is downregulated in various cancers, which can affect tumor initiation and maintenance. Herein, we found that miR-99a was downregulated in NSCLC tissues and suppressed tumor metastasis of NSCLC cells. Down-regulation of miR-99a is significantly associated with last-stage and tumor metastasis in NSCLC patients. Further functional experiments found that overexpression of miR-99a inhibit cell proliferation, migration, and invasion of NSCLC cells in vitro and tumor metastasis of NSCLC in vivo. In addition, we also found that AKT1 is directly involved in miR-99a-mediated tumor suppression. Restored the expression of AKT1 partially abolished the suppressive effects miR-99a on proliferation and invasion of NSCLC cells. Collectively, our data suggest that miR-99a plays an important role in the tumorigenesis and metastasis of NSCLC and may serve as a therapeutic target to avoid dissemination of NSCLC cells.

Novel missense mutation in WNT6 in 100 couples with unexplained recurrent miscarriage.

STUDY QUESTION: Do mutations and/or polymorphisms in coding sequences in Wingless-Type MMTV Integration Site Family, Member 6 (WNT6) play a role in unexplained recurrent miscarriage (unexplained RM) in Chinese couples? SUMMARY ANSWER: We found four mutations in the coding sequences of WNT6 which appear to exist in a small proportion of Chinese women with unexplained RM. WHAT IS KNOWN ALREADY: WNT6 has been proved to be essential for stromal cell proliferation during decidualization in mice, but in humans WNT6 has not been studied in recurrent miscarriage populations. STUDY DESIGN, SIZE, DURATION: For this study, 100 couples with unexplained RM (at least three or more unexplained spontaneous miscarriages), and 100 ethnically matched fertile couples (at least one live birth and no history of pregnancy pathologies) were recruited. All the participants were chosen over a 7-year period from the National Research Center for Assisted Reproductive Technology and Reproductive Genetics at Shandong University, Jinan, China. PARTICIPANTS/MATERIALS, SETTING, METHODS: Patients were recruited following extensive clinical studies. Genomic DNA was isolated from peripheral blood. Mutation analysis in the coding regions of WNT6 was performed by PCR amplification and DNA sequences testing in all participants. Functional effects of missense variants were predicted using Polyphen-2 and sorting intolerant from tolerant (SIFT). MAIN RESULTS AND THE ROLE OF CHANCE: Four rare novel mutations, including one missense mutation, were found in intron 1, exon 3 and the 3' untranslated region of WNT6 in four women with unexplained RM. Gene software predictions showed that the missense mutation in exon 3 could alter the function of WNT6. No mutations or polymorphisms were detected in the male partners of the unexplained RM patients or in the fertile controls. To further validate the findings, we continued to screen this missense mutation site in another 100 peripheral blood samples of normal fertile females, and there was still no positive result. LIMITATIONS, REASONS FOR CAUTION: There is no direct evidence to validate whether these novel mutations discovered in the present research are related to unexplained RM. Further studies are warranted to investigate the role of WNT6 in unexplained RM, including larger studies in an independent group. WIDER IMPLICATIONS OF THE FINDINGS: These results provide evidence to suggest the importance of WNT6 in reproductive failure and may support the hypothesis that WNT6 is essential for stromal cell proliferation during decidualization. STUDY FUNDING/COMPETING INTERESTS: This work was supported by Science and Technology Development Planning of Shandong (2013GGE27001), the National Natural Science Foundation of China (81300459), the Science Projection of Bureau of Public Health in Weifang (2012044) and the Science Research Foundation Item of No-earnings Health Vocation. The authors have no competing interests to declare.