Spin-orbit microlaser emitting in a four-dimensional Hilbert space.

A step towards the next generation of high-capacity, noise-resilient communication and computing technologies is a substantial increase in the dimensionality of information space and the synthesis of superposition states on an N-dimensional (N > 2) Hilbert space featuring exotic group symmetries. Despite the rapid development of photonic devices and systems, on-chip information technologies are mostly limited to two-level systems owing to the lack of sufficient reconfigurability to satisfy the stringent requirement for 2(N - 1) degrees of freedom, intrinsically associated with the increase of synthetic dimensionalities. Even with extensive efforts dedicated to recently emerged vector lasers and microcavities for the expansion of dimensionalities1-10, it still remains a challenge to actively tune the diversified, high-dimensional superposition states of light on demand. Here we demonstrate a hyperdimensional, spin-orbit microlaser for chip-scale flexible generation and manipulation of arbitrary four-level states. Two microcavities coupled through a non-Hermitian synthetic gauge field are designed to emit spin-orbit-coupled states of light with six degrees of freedom. The vectorial state of the emitted laser beam in free space can be mapped on a Bloch hypersphere defining an SU(4) symmetry, demonstrating dynamical generation and reconfiguration of high-dimensional superposition states with high fidelity.

OsGEX3 affects anther development and improves osmotic stress tolerance in rice.

MAIN CONCLUSION: Overexpression and loss of function of OsGEX3 reduce seed setting rates and affect pollen fertility in rice. OsGEX3 positively regulates osmotic stress response by regulating ROS scavenging. GEX3 proteins are conserved in plants. AtGEX3 encodes a plasma membrane protein that plays a crucial role in pollen tube guidance. However, the function of its homolog in rice, OsGEX3, has not been determined. Our results demonstrate that OsGEX3 is localized in the plasma membrane and the nucleus as shown by a transiently transformed assay using Nicotiana benthamiana leaves. The up-regulation of OsGEX3 was detected in response to treatments with polyethylene glycol (PEG) 4000, hydrogen peroxide, and abscisic acid (ABA) via RT-qPCR analysis. Interestingly, we observed a significant decline in the seed setting rates of OsGEX3-OE lines and mutants, compared to the wild type. Further investigations reveal that overexpression and loss of function of OsGEX3 affect pollen maturation. TEM observation revealed a significant decrease in the fertile pollen rates of OsGEX3-OE transgenic lines and Osgex3 mutants due to a delay in pollen development at the late vacuolated stage. Overexpression of OsGEX3 improved osmotic stress and oxidative stress tolerance by enhancing reactive oxygen species (ROS) scavenging in rice seedlings, whereas Osgex3 mutants exhibited an opposite phenotype in osmotic stress. These findings highlight the multifunctional roles of OsGEX3 in pollen development and the response to abiotic stress. The functional characterization of OsGEX3 provides a fundamental basis for rice molecular breeding and can facilitate efforts to cultivate drought resistance and yield-related varieties.

Quantitative systems pharmacology modeling of HER2-positive metastatic breast cancer for translational efficacy evaluation and combination assessment across therapeutic modalities.

HER2-positive (HER2+) metastatic breast cancer (mBC) is highly aggressive and a major threat to human health. Despite the significant improvement in patients' prognosis given the drug development efforts during the past several decades, many clinical questions still remain to be addressed such as efficacy when combining different therapeutic modalities, best treatment sequences, interindividual variability as well as resistance and potential coping strategies. To better answer these questions, we developed a mechanistic quantitative systems pharmacology model of the pathophysiology of HER2+ mBC that was extensively calibrated and validated against multiscale data to quantitatively predict and characterize the signal transduction and preclinical tumor growth kinetics under different therapeutic interventions. Focusing on the second-line treatment for HER2+ mBC, e.g., antibody-drug conjugates (ADC), small molecule inhibitors/TKI and chemotherapy, the model accurately predicted the efficacy of various drug combinations and dosing regimens at the in vitro and in vivo levels. Sensitivity analyses and subsequent heterogeneous phenotype simulations revealed important insights into the design of new drug combinations to effectively overcome various resistance scenarios in HER2+ mBC treatments. In addition, the model predicted a better efficacy of the new TKI plus ADC combination which can potentially reduce drug dosage and toxicity, while it also shed light on the optimal treatment ordering of ADC versus TKI plus capecitabine regimens, and these findings were validated by new in vivo experiments. Our model is the first that mechanistically integrates multiple key drug modalities in HER2+ mBC research and it can serve as a high-throughput computational platform to guide future model-informed drug development and clinical translation.

Enantioselective adsorption of ibuprofen enantiomers using chiral-active carbon nanoparticles induced S-α-methylbenzylamine.

The chiral media is crucial to the chiral recognition and separation of enantiomers. In this study, we report the preparation of novel chiral carbon nanoparticles (CCNPs) via surface passivation using glucose as the carbon source and S-(-)-α-methylbenzylamine as the chiral ligand. The structures of the obtained CCNPs are characterized via FT-IR, Raman spectroscopy, DLS, XPS, XRD, TEM, and zeta potential analysis. These CCNPs could be employed as the chiral adsorbent and used for the enantioselective adsorption of the ibuprofen enantiomers. The results demonstrated that the CCNPs could selectively adsorb R-enantiomer from ibuprofen racemate solution and give an enantiomeric excess (e.e.) of about 50% under an optimal adsorption condition. Moreover, the regeneration efficiency of the CCNPs remained above e.e. of 43% after the fifth cycle. The present work confirmed that the prepared CCNPs show great potential in the enantioselective separation of ibuprofen racemate.

Efficacy of acellular fish skin graft in the management of chronic ulcer: a systematic review and meta-analysis.

BACKGROUND: The wounds failing to heal through a timely and orderly standard of care (SOC) treatment are considered as chronic wounds, which add significant burden to healthcare systems around the world. SOC treatment has been commonly applied for management of chronic wounds, but SOC alone may not be adequate to heal all ulcers effectively. Fish skin graft (FSG) is a xenogenic skin substitute which could be used for accelerating skin healing. The current study was performed with the view of evaluating the effectiveness of FSG as an adjuvant treatment of SOC for chronic ulcer treatment. METHODS: Two authors independently searched the following electronic databases: PubMed, Embase, and CENTRAL, using keywords including "diabetic foot ulcer," "fish skin graft," and "wound healing." Clinical studies that evaluated the clinical outcomes of FSG in treatment of chronic ulcers were included in this meta-analysis. Random- or fixed-effect modeled meta-analyses were performed according to the heterogeneity test result (i.e., I2), to analyze the clinical outcome of FSG. RESULTS: A total of 8 studies were included in qualitative synthesis and meta-analysis, with 145 patients treated by SOC and 245 patients treated by SOC plus FSG. There was no significant difference between two groups for time to healing (MD = 1.99, 95% CI: -3.70~7.67, p = 0.493). The complete healing rate was significantly higher in FSG group compared with SOC alone (OR = 3.44, 95% CI: 2.03~5.82, p < 0.001***). Mean percentage area reduction (PAR) was reported in six studies, with a range of 71.6~97.3%. However, many of these studies did not report the value of standard deviation (SD), so we could not pool the data. No significantly different ulcer recurrence rate (RR = 0.60, 95% CI: 0.07~5.27, p = 0.645) and severe adverse events (SAEs) risk (RR = 1.67, 95% CI: 0.42~6.61, p = 0.467) were found between two groups. CONCLUSIONS: The application of FSG treatment for patients with chronic ulcers that do not respond well to SOC management could significantly increase the complete healing rate compared with SOC alone, without increased recurrence rate and SAEs risk.

The impact of nurses' experiences of hospital violence on resilience: A mediated moderation model.

AIMS: This study aims to investigate the impact of nurses' experiences of hospital violence on resilience, the mediating effect of trust in patients and the moderating effect of organizational trust. BACKGROUND: Despite belonging to the central part of health care worldwide and being the leading provider of medical services, nurses are often subjected to hospital violence, which affects their physical and mental well-being. Trust is a high-order mechanism that encourages positive thinking and personal and professional development. However, research into the impact of trust on resilience concerning nurses' experiences of hospital violence is limited. METHODS: The participants were 2331 nurses working in general hospitals in China. A cross-sectional survey was conducted, and data were collected via questionnaires from July to October 2022 and analysed using SPSS 25.0 and SPSS PROCESS 3.3 macros. This study was prepared and reported according to the STROBE checklist. RESULTS: Mean trust in patients was 48.00 ± 10.86 (12-60), mean organizational trust was 56.19 ± 8.90 (13-65) and mean resilience was 78.63 ± 19.26 (0-100). Nurses' experience of hospital violence had a direct negative effect on resilience (ß = -.096, p = .871), a significant adverse effect on trust in patients (ß = -3.022, p < .001) and a significant positive effect on trust in patients on resilience (ß = 1.464, p < .001). Trusting patients played a mediating role. The significant moderating effect of organizational trust between experience of hospital violence and trust in patients was moderated by a mediating effect index of -0.1867 (95% CI = [-0.3408, -0.0345]). CONCLUSIONS: Nurses' experience of hospital violence exerted a negative effect on resilience, trust in patients had a fully mediated effect and organizational trust had a significant moderating influence in the pathway from nurses' experience of hospital violence to patients' trust-mediated resilience. IMPLICATIONS FOR NURSING AND HEALTH POLICY: This study highlights the impact of nurses' experiences of hospital violence on resilience and explores the importance of trust from the nurses' perspective. Measures taken by managers to provide nurses with a safe, trusting and positive work environment can be highly beneficial in enhancing nurse resilience.

The RNA binding protein OsLa influences grain and anther development in rice.

La proteins are found widely in eukaryotes and play a variety of vital roles. AtLa1 has been identified as an La protein that is necessary for embryogenesis in Arabidopsis; however, the existence and biological functions of La proteins in rice (Oryza sativa L.) remain unclear. In this study, we identified and characterized two La proteins in rice that are homologous to AtLa1 and named them OsLa1 and OsLa2. Both the OsLa1 and OsLa2 genes encode RNA-binding proteins with an La domain and two RNA-binding domains. Mutant OsLa1 reduced grain length and pollen fertility, whereas OsLa1 overexpression caused the opposite phenotypes. Further experiments indicated that OsLa1 modulates grain size by influencing cell expansion. Interestingly, mutant OsLa2 resulted in thin grains with decreased weight and a low seed-setting rate. We also found that OsLa1 interacted with OsLa2 and that both OsLa1 and OsLa2 interacted with OseIF6.1, a eukaryotic translation initiation factor involved in ribosome biogenesis. In addition, OsLa1 was able to bind to OseIF6.1 mRNA to modulate its expression. Complete OseIF6.1 knockout caused lethality and OseIF6.1/oseif6.1 heterozygous plants displayed low fertility and low seed setting. Together, our results enrich our knowledge of the role of La proteins in rice growth and development, as well as the relationship between La and eIF6 in rice.

Robust Zero Modes in Non-Hermitian Systems without Global Symmetries.

We present an approach to achieve zero modes in lattice models that do not rely on any symmetry or topology of the bulk, which are robust against disorder in the bulk of any type and strength. Such symmetry-free zero modes (SFZMs) are formed by attaching a single site or small cluster with zero mode(s) to the bulk, which serves as the "nucleus" that expands to the entire lattice. We identify the requirements on the couplings between this boundary and the bulk, which reveals that this approach is intrinsically non-Hermitian. We then provide several examples with either an arbitrary or structured bulk, forming spectrally embedded zero modes in the bulk continuum, midgap zero modes, and even restoring the "zeroness" of coupling or disorder-shifted topological corner states. Focusing on viable realizations using photonic lattices, we show that the resulting SFZM can be observed as the single lasing mode when optical gain is applied to the boundary.

Two-Dimensional Reconfigurable Non-Hermitian Gauged Laser Array.

Topological effects in photonic non-Hermitian systems have recently led to extraordinary discoveries including nonreciprocal lasing, topological insulator lasers, and topological metamaterials, to mention a few. These effects, although realized in non-Hermitian systems, are all stemming from their Hermitian components. Here we experimentally demonstrate the topological skin effect and boundary sensitivity, induced by the imaginary gauge field in a two-dimensional laser array, which are fundamentally different from any Hermitian topological effects and intrinsic to open systems. By selectively and asymmetrically injecting gain into the system, we have synthesized an imaginary gauge field on chip, which can be flexibly reconfigured on demand. We show not only that the non-Hermitian topological features remain intact in a nonlinear nonequilibrium system, but also that they can be harnessed to enable persistent phase locking with intensity morphing. Our work lays the foundation for a dynamically reconfigurable on-chip coherent system with robust scalability, attractive for building high-brightness sources with arbitrary intensity profiles.

Roles of microRNAs and exosomes in Helicobacter pylori associated gastric cancer.

Helicobacter pylori (H. pylori) is a common pathogen that infects more than half of the world's population. Its infection can not only lead to a variety of gastrointestinal diseases, such as chronic gastritis and gastric cancer (GC) but also be associated with many extra-gastrointestinal diseases. Exosomes, as a new intercellular information transmission medium, can carry biological signal molecules such as microRNAs (miRNAs) to regulate a variety of cellular physiological activities and are involved in multiple cancer processes. In this article, we provide a systematic review on the role of exosomal miRNAs in H. pylori-associated GC.

Ursane-Type Triterpenes with a Phenylpropanoid Unit from Camellia ptilosperma and Evaluation of Their Cytotoxic Activities.

Six new ursane-type triterpenes with a phenylpropanoid unit and five known oleanane-type triterpenes were isolated from the leaves of Camellia ptilosperma. The undescribed compounds were identified by analysis of 1D and 2D NMR and HRESIMS spectroscopic data as ptilospermanols A-F. The cytotoxicity of new compounds against six human cancer cell lines and three mouse tumor cell lines was evaluated by MTT assay.

Changes in Diversity and Composition of Rhizosphere Bacterial and Fungal Community between Resistant and Susceptible Pakchoi under Plasmodiophora brassicae.

Plasmodiophora brassicae (P. brassicae) is a soil-born pathogen worldwide and can infect most cruciferous plants, which causes great yield decline and economic losses. It is not well known how microbial diversity and community composition change during P. brassicae infecting plant roots. Here, we employed a resistant and a susceptible pakchoi cultivar with and without inoculation with P. brassicae to analyze bacterial and fungal diversity using 16S rRNA V3-V4 and ITS_V1 regions, respectively. 16S rRNA V3-V4 and ITS_V1 regions were amplified and sequenced separately. Results revealed that both fungal and bacterial diversity increased, and composition was changed in the rhizosphere soil of the susceptible pakchoi compared with the resistant cultivar. In the four groups of R_mock, S_mock, R_10d, and S_10d, the most relatively abundant bacterium and fungus was Proteobacteria, accounting for 61.92%, 58.17%, 48.64%, and 50.00%, respectively, and Ascomycota, accounting for 75.11%, 63.69%, 72.10%, and 90.31%, respectively. A total of 9488 and 11,914 bacteria were observed uniquely in the rhizosphere soil of resistant and susceptible pakchoi, respectively, while only 80 and 103 fungi were observed uniquely in the correlated soil. LefSe analysis showed that 107 and 49 differentially abundant taxa were observed in bacteria and fungi. Overall, we concluded that different pakchoi cultivars affect microbial diversity and community composition, and microorganisms prefer to gather around the rhizosphere of susceptible pakchoi. These findings provide a new insight into plant-microorganism interactions.

Triterpenes and Pheophorbides from Camellia ptilosperma and Their Cytotoxicity, Photocytotoxicity, and Photodynamic Antibacterial Activity.

Phytochemical investigation of the leaves of Camellia ptilosperma S. Y. Liang et Q. D. Chen led to the isolation of ten undescribed compounds, including six new triterpenes (1-6) and four new pheophorbide-related compounds (7-10). Meanwhile, the cytotoxic activity of the six triterpenes against six cancer cell lines was evaluated by MTT assay. Compound 2 showed potent cytotoxicity toward HepG2 cells with an IC50 value of 2.57 µM. Compounds 4 and 5 exhibited cytotoxicity against MDA-MB231 cells, with IC50 values of 11.31 and 5.52 µM, respectively. Additionally, the cytotoxicity of four new pheophorbides against these cancer cells was evaluated both in the presence and absence of light treatment. Compound 7 exhibited exceptional photocytotoxicity against Hela, MCF-7, and A549 cells, with IC50 values of 0.43 µM, 0.28 µM, and 0.92 µM, respectively. Compound 10 demonstrated significant photodynamic cytotoxic activity against BEL-7402 and HepG2 cells with IC50 values of 0.77 µM and 0.33 µM, respectively. The photodynamic antibacterial activity of 7-10 was also tested for S. aureus, E. coli, K. pneumoniae, and P. aeruginosa under direct illumination. Compounds 8 and 10 exhibited sensitivity to E. coli and demonstrated a photodynamic antibacterial effect, with a MIC value of 0.625 µM.

[Mechanism of nuclear protein 1 in the resistance to axitinib in clear cell renal cell carcinoma].

OBJECTIVE: To explore the potential mechanism of resistance to axitinib in clear cell renal cell carcinoma (ccRCC), with a view to expanding the understanding of axitinib resistance, facilitating the design of more specific treatment options, and improving the treatment effectiveness and survival prognosis of patients. METHODS: By exploring the half maximum inhibitory concentration (IC50) of axitinib on ccRCC cell lines 786-O and Caki-1, cell lines resistant to axitinib were constructed by repeatedly stimulated with axitinib at this concentration for 30 cycles in vitro. Cell lines that were not treated by axitinib were sensitive cell lines. The phenotypic differences of cell proliferation and apoptosis levels between drug resistant and sensitive lines were tested. Genes that might be involved in the drug resistance process were screened from the differentially expressed genes that were co-upregulated in the two drug resistant lines by transcriptome sequencing. The expression level of the target gene in the drug resistant lines was verified by real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot (WB). The expression differences of the target gene in ccRCC tumor tissues and adjacent tissues were analyzed in the Gene Expression Profiling Interactive Analysis (GEPIA) public database, and the impact of the target gene on the prognosis of ccRCC patients was analyzed in the Kaplan-Meier Plotter (K-M Plotter) database. After knocking down the target gene in the drug resistant lines using RNA interference by lentivirus vector, the phenotypic differences of the cell lines were tested again. WB was used to detect the levels of apoptosis-related proteins in the different treated cell lines to find molecular pathways that might lead to drug resistance. RESULTS: Cell lines 786-O-R and Caki-1-R resistant to axitinib were successfully constructed in vitro, and their IC50 were significantly higher than those of the sensitive cell lines (10.99 µmol/L, P < 0.01; 11.96 µmol/L, P < 0.01, respectively). Cell counting kit-8 (CCK-8) assay, colony formation, and 5-ethynyl-2 '-deoxyuridine (EdU) assay showed that compared with the sensitive lines, the proliferative ability of the resistant lines decreased, but apoptosis staining showed a significant decrease in the level of cell apoptosis of the resistant lines (P < 0.01). Although resistant to axitinib, the resistant lines had no obvious new replicated cells in the environment of 20 µmol/L axitinib. Nuclear protein 1 (NUPR1) gene was screened by transcriptome sequencing, and its RNA (P < 0.0001) and protein expression levels significantly increased in the resistant lines. Database analysis showed that NUPR1 was significantly overexpressed in ccRCC tumor tissue (P < 0.05); the ccRCC patients with higher expression ofNUPR1had a worse survival prognosis (P < 0.001). Apoptosis staining results showed that knockdown ofNUPR1inhibited the anti-apoptotic ability of the resistant lines to axitinib (786-O, P < 0.01; Caki-1, P < 0.05). WB results showed that knocking downNUPR1decreased the protein level of B-cell lymphoma-2 (BCL2), increased the protein level of BCL2-associated X protein (BAX), decreased the protein level of pro-caspase3, and increased the level of cleaved-caspase3 in the resistant lines after being treated with axitinib. CONCLUSION: ccRCC cell lines reduce apoptosis through theNUPR1 -BAX/ BCL2 -caspase3 pathway, which is involved in the process of resistance to axitinib.

The impact of resilience on clinical nurses' moral courage during COVID-19: A moderated mediation model of ethical climate and moral distress.

AIM: The purpose of this study was to explore whether clinical ethical climate mediates the relationship between resilience and moral courage in a population of clinical nurses during COVID-19, and if moral distress faced by nurses is a moderating factor. BACKGROUND: Resilience can help nurses maintain their personal health during COVID-19 when they face great physical and psychological shock and are prone to health problems. Moral courage, as an ethical competency, helps nursing staff in adhering to the principles and values of professional ethics. There is a strong correlation between resilience and moral courage, but the mechanism by which resilience contributes to moral courage is unclear. METHOD: A cross-sectional study research is designed. Three hundred thirty clinical nurses from six hospitals in Beijing, Sichuan, and Fujian of China were included between August 2021 and March 2022. The survey instruments include the Nurses' Moral Courage Scale (NMCS), Connor-Davidson Resilience Scale (CD-RISC), Moral Distress Scale-Revised (MDS-R), and Hospital Ethical Climate Scale (HECS). RESULTS: Ethical climate mediates 15% of the relationship between resilience and moral courage. The association between resilience and ethical climate, as well as the indirect relationship between resilience and moral courage, was modified by moral distress. DISCUSSION: This study investigated the mechanisms by which resilience affects moral courage in clinical nurses in the context of COVID-19, suggesting that moral courage can be increased by alleviating moral distress and increasing ethical climate. IMPLICATIONS FOR NURSING AND HEALTH POLICY: This study confirms the mediating effect of moral climate on the relationship between resilience and moral courage, as well as the moderating effect of moral distress. Hospital policymakers should value nurses' psychological resilience and moral courage, develop effective policies to prevent and manage stressors, build social support systems, and create a positive ethical climate.

Surgical strategy and outcome in patients with bilateral proliferative diabetic retinopathy.

OBJECTIVES: To investigate the current surgery strategies for bilateral proliferative diabetic retinopathy (PDR), as well as the surgical outcomes of patients with bilateral PDR who underwent pars plana vitrectomy (PPV). MATERIALS: Patients undergoing bilateral vitrectomy for PDR from January 2019 to December 2020 at The Eye Hospital of Wenzhou Medical University were enrolled. Clinical data were collected from the electronic medical records. Factors associated with the time interval between the surgeries on two eyes and postoperative visual outcomes were analyzed. RESULTS: In total, 152 patients with bilateral PDR who underwent bilateral PPV were included in this analysis. Mean age was 53.7 ± 11.4 years. Compared with second-surgery eyes, 60.5% of first-surgery eyes had worse preoperative best-corrected visual acuity (BCVA). The overall PPV time (median, quartile range) between first and second surgeries eye was 1.40 (0.70, 3.15) months. Multivariate analysis showed that the preoperative BCVA of the second-surgery eye had a significant effect on the inter-surgery time interval (P = 0.048). First-surgery eyes had greater vision improvement than second-surgery eyes (Difference of the logarithm of the minimum angle of resolution [LogMAR] BCVA: - 1.00 [- 1.48, - 0.12] versus 0.00 [- 1.30, 0.00], respectively, P < 0.001), especially when eyes with poorer BCVA underwent PPV first (- 1.15 [- 1.87, - 0.54] versus 0.00 [- 0.70, 0.00], respectively, P < 0.001). CONCLUSIONS: Visual acuity is a significant factor that influences surgical strategies, including both surgery order and interval, for patients with bilateral PDR. The eyes operated upon first show more vision improvement due to prompt surgery.

Imaginary Gauge Transformation in Momentum Space and Dirac Exceptional Point.

An imaginary gauge transformation is at the core of the non-Hermitian skin effect. Here, we show that such a transformation can be performed in momentum space as well, which reveals that certain gain- and loss-modulated systems in their parity-time (PT) symmetric phases are equivalent to Hermitian systems with real potentials. Our analysis in momentum space also distinguishes two types of exceptional points (EPs) in the same system. Besides the conventional type that leads to a PT transition upon the continuous increase of gain and loss, we find real-valued energy bands connected at a Dirac EP in hybrid dimensions, consisting of a spatial dimension and a synthetic dimension for the gain and loss strength.

Perceptions of pelvic floor dysfunction and rehabilitation care amongst women in southeast China after radical hysterectomy: a qualitative study.

OBJECTIVE: To investigate the perceptions of pelvic floor dysfunction (PFD) and rehabilitation care amongst women after radical hysterectomy and to explore ways to improve quality of care. METHODS: Thirty-six women who underwent radical hysterectomy at a hospital in southeast China were enrolled via purposive sampling. Semi-structured in-depth interviews were conducted. The texts were analysed via qualitative content analysis. RESULTS: Four themes were obtained: serious lack of knowledge, heavy psychological burden, different coping strategies and great eagerness to receive multiparty support on PFD rehabilitation care. CONCLUSION: The society and professional staff should strengthen health education on PFD. Professionals should offer education before and after surgery and actively provide rehabilitation consultation to promote the availability of rehabilitation to support women with PFD rehabilitation care. In addition, family-centred care is an important way to support women to return to normal life, and women's need for family support should be more actively expressed. Moreover, knowledge of medical insurance should be popularised, especially in rural areas in China.

Hsa-miRNA-143-3p regulates the odontogenic differentiation of human stem cells from the apical papilla by targeting NFIC.

AIM: To evaluate the effects of hsa-miRNA-143-3p on the cytodifferentiation of human stem cells from the apical papilla (hSCAPs) and the post-transcriptional regulation of Nuclear factor I-C (NFIC). METHODOLOGY: miRNA expression profiles in human immature permanent teeth and during hSCAP differentiation were examined. hSCAPs were treated with miR-143-3p overexpression or silencing viruses, and the proliferation and odontogenic and osteogenic differentiation of these stem cells, and the involvement of the NFIC pathway, were investigated. Luciferase reporter and NFIC mutant plasmids were used to confirm NFIC mRNA as a direct target of miR-143-3p. NFIC expression analysis in the miR-143-3p overexpressing hSCAPs was used to investigate whether miR-143-3p functioned by targeting NFIC. Student's t-test and chi-square tests were used for statistical analysis. RESULTS: miR-143-3p expression was screened by microarray profiling and was found to be significantly reduced during hSCAP differentiation (p < .05). Overexpression of miR-143-3p inhibited the mineralization of hSCAPs significantly (p < .05) and downregulated the levels of odontogenic differentiation markers (NFIC [p < .05], DSP [p < .01] and KLF4 [p < .01]), whereas silencing of miR-143-3p had the opposite effect. The luciferase reporter gene detection and bioinformatic approaches identified NFIC mRNA as a potential target of miR-143-3p. NFIC overexpression reversed the inhibitory effect of miR-143-3p on the odontogenic differentiation of hSCAPs. CONCLUSIONS: miR-143-3p maintained the stemness of hSCAPs and modulated their differentiation negatively by directly targeting NFIC. Thus, inhibition of this miRNA represents a potential strategy to promote the regeneration of damaged tooth roots.

Family-based analysis of -675 4G/5G polymorphism in the PAI-1 gene of polycystic ovary syndrome in Chinese population.

Previous studies have shown that 4G/5G polymorphism in promoter region of plasminogen activator inhibitor-1 (PAI-1) gene can affect insulin sensitivity by elevating the level and activity of plasma PAI-1. In order to elucidate the relationship between the polymorphism of PAI-1 gene and polycystic ovary syndrome (PCOS), we used transmission disequilibrium test (TDT) to study the family of PCOS. Eight hundred and fifty-five participants consisting of 285 trios (mother, father and offspring with PCOS) were recruited at the Center of Reproductive Medicine, Shandong University from July 2007 to August 2014. 4G/5G polymorphism of PAI-1 gene was genotyped using direct sequencing protocol and TDT was used to analyse the association between PAI-1 gene and PCOS. Though the 5G allele in PAI-1 gene was overtransmitted in families, no statistical significance existed and there was no association between PAI-1 gene and PCOS, indicating that PAI-1 gene was unlikely to play a major role in the aetiology of PCOS in Chinese population.Impact StatementWhat is already known on this subject? Some studies have shown that 4G/5G polymorphism in promoter region of plasminogen activator inhibitor-1 (PAI-1) gene can affect insulin sensitivity by elevating the level and activity of plasma PAI-1, participating in the formation of insulin resistance (IR).What do the results of this study add? Though the 5G allele in PAI-1 gene was overtransmitted in families, no statistical significance existed and there was no association between PAI-1 gene and polycystic ovary syndrome (PCOS).What are the implications of these findings for clinical practice and/or further research? PAI-1 gene was unlikely to play a major role in the aetiology of PCOS.