[Polycystic ovary syndrome is positively correlated with periodontitis: a prospective study].

OBJECTIVE: To explore the correlation between polycystic ovary syndrome (PCOS) and periodontitis in light of cytokines levels, sex hormone levels and metabolism-related indicators and their changes during progression of the two diseases. METHODS: Twenty healthy subjects and 40 patients diagnosed with PCOS underwent full-mouth periodontal examinations to obtain full-mouth plaque score (FMPS), gingival bleeding index of probing (BOP), probing depth (PD), and clinical attachment level (CAL). The participants were divided into Group A without periodontitis or PCOS (n=15), Group B with PCOS but without periodontitis (n=28), Group C with periodontitis but without PCOS (n=5), and Group D with both diseases (n=12). Serum levels of luteinizing hormone/follicle stimulating hormone (LH/FSH), testosterone, prolactin, progesterone and estradiol, and the levels of interleukin 6 (IL-6), IL-17A, tumor necrosis factor α and matrix metalloproteinase 8 (MMP-8) in both serum and saliva samples were measured at the time of enrolment and at 3 and 6 months after enrolment and compared among the 4 groups. RESULTS: Serum MMP-8 level was significantly higher in Group B than in Group A (P<0.05). Salivary MMP-8 level was significantly higher in Group D than in Group B (P<0.05). Salivary MMP-8, LH, and LH/FSH levels and serum and salivary IL-6 and progesterone levels all tended to increase in the 6 months after enrollment (OR>1, P<0.05). During the follow-up period, serum IL-6 levels differed significantly between the non-PCOS groups (A and C) and PCOS groups (B and D)(P<0.05); serum IL-6 and salivary MMP-8 levels differed significantly between the non-periodontitis groups (A and B) and periodontitis groups (C and D)(P<0.05). Spearman correlation analysis indicated positive correlations of LH and LH/FSH with PD (P<0.05); testosterone and LH/FSH were positively correlated with serum MMP-8 levels (P<0.05), and PD, BOP and FMPS were positively correlated with salivary MMP-8 levels (P<0.01). CONCLUSION: There is a correlation between PCOS and periodontitis, and their progression is accompanied by changes in serum and salivary levels of pro-inflammatory cytokines and serum sex hormones.

Chinese family care partners of older adults in Canada have grit: A qualitative study.

AIM: To explain the process taken by Chinese family care partners of older adults in the Greater Toronto Area, Canada, to access health and social services in their communities. The research question was: What mechanisms and structures impact the agency of Chinese family care partners of older adults, in the process of assisting them to access health and social services? DESIGN: This qualitative study was informed by critical realism. METHODS: Chinese family care partners of older adults in the Greater Toronto Area, Canada, were interviewed from August 2020 to June 2021. Transcripts underwent thematic analysis. FINDINGS: Twenty-eight Chinese family care partners expressed a firm commitment to maintain caregiving conditions and to judiciously access health and social services. Their commitment was made up of three parts: (a) legislative and cultural norms of family, work, and society; (b) their perseverance to fill gaps with limited social and financial resources; (c) the quality of their relationship to, and illness trajectory of the older adults. The social structures created tension in how Chinese family care partners made decisions, negotiated resources, and ultimately monitored and coordinated timely access with older adults. CONCLUSION: Participants' commitment and perseverance were conceptualized as "grit," central to their agency to conform to legislative and cultural norms. Moreover, findings support grit's power to motivate and sustain family caregiving, in order for older adults to age in place as long as possible with finite resources. IMPLICATIONS FOR THE PROFESSION: This study highlights the importance of cultural awareness education for nurses, enabling continuity of care at a systems level and for a more resilient healthcare system. IMPACT: Family care partners' grit may be crucial for nurses to harness when together, they face limited access to culturally appropriate health and social services in a system grounded in values of equity and inclusion, as in Canada. REPORTING METHOD: When writing this manuscript, we adhered to relevant EQUATOR guidelines of the Consolidated Criteria for Reporting Qualitative Research (COREQ). PATIENT OR PUBLIC INVOLVEMENT AND ENGAGEMENT: No patient or public involvement.

Three-Dimensional Fracture Analysis in Functionally Graded Materials Using the Finite Block Method in Strong Form.

In this paper, the application of the strong-form finite block method (FBM) to three-dimensional fracture analysis with functionally graded materials is presented. The main idea of the strong-form FBM is that it transforms the arbitrary physical domain into a normalized domain and utilizes the direct collocation method to form a linear system. Using the mapping technique, partial differential matrices of any order can be constructed directly. Frameworks of the strong-form FBM for three-dimensional problems based on Lagrange polynomial interpolation and Chebyshev polynomial interpolation were developed. As the dominant parameters in linear elastic fracture mechanics, the stress intensity factors with functionally graded materials (FGMs) were determined according to the crack opening displacement criteria. Several numerical examples are presented using a few blocks to demonstrate the accuracy and efficiency of the strong-form FBM.

Influence of Taper surface topographies on contact deformation and stresses.

The role of bore and trunnion surface topography on the failure rate of total hip joint replacements due to trunnionosis is not clear despite significant variations in the design of taper components between manufacturers. Taper surface topography, along with other taper design parameters such as clearance, diameter, and assembly force, determine the initial interlock of the contacting surfaces after assembly; this has been related to relative motions that can cause fretting and corrosion at the taper interface. However, in most in-silico parametrical taper studies associated with taper micromotions, the bore and trunnion surfaces have been simplified using a flat surface and/or sinusoidal functions to mimic the surface roughness. The current study tests the hypothesis that the use of simple geometrical functions for the taper surface topography can predict the surface mechanics developed in assembled tapers. Measured and simulated surfaces of bores and trunnions were characterised using common roughness parameters and spectral density estimations. Using the same characterised surface profiles, 2D Finite Element (FE) models of CoCr alloy femoral heads and Ti alloy trunnions were developed. Models simulated assembly conditions at different resultant forces ranging from 0.5 to 4.0 kN, contact conditions were determined and associated with their topographical characteristics. Measured surfaces of bore and trunnion components comprise up to seven dominant spatial frequencies. Flattening of the trunnion microgrooved peaks was observed during the assembly of the taper. When the femoral head bore and trunnion topography were both considered a reduced number of microgrooved peaks were in contact, from 51 in an idealised taper surfaces to 35 in measured surfaces using an assembly reaction force of 4 kN. The contact points in the models developed high plastic strains, which were greater than that associated with failure of the material. Results showed that line and sine wave functions over estimate contact points at the taper interface compared to those surfaces that consider roughness and peak variation. These findings highlight the important role of modelling the full surface topography on the taper contact mechanics, as surface variations in the roughness and waviness change the performance of tapers.

Comparison of Risk Factors of Falling for Psychiatric Inpatients and General Ward Inpatients Who Had Fallen.

BACKGROUND: For psychiatric patients, the issue of falling is complex. AIM: The objective of this study was to compare the risk factors for falling in psychiatric inpatients and general ward inpatients who had fallen. METHODS: The researchers first derived official fall records for 122 psychiatric inpatients and then selected 122 psychiatric inpatients who had not fallen as well as 122 general ward patients who had fallen, matched for gender, age, and length of hospital stay at the time of the fall incident. RESULTS: After controlling other variables, multinomial logistic regression analysis revealed that psychiatric inpatients who had fallen and had dizziness (odds ratio [OR] = 7.11, p < .001), had an unsteady gait (OR = 1.97, p = .030), or were not using aids (OR = 0.42, p = .042) were at greater risk of falling than those who had not fallen. The researchers also found that general ward inpatients who had fallen and had higher Charlson Comorbidity Index scores (OR = 1.77, p < .001), were clear-headed (OR = 27.15, p = .001), had dizziness (OR = 11.55, p < .001), were unable to walk (OR = 64.28, p < .001), or were using aids (OR = 3.86, p = .001) were at greater risk of falling than those who had not fallen before. CONCLUSIONS: The causes of falling among psychiatric inpatients and general ward inpatients are different. Medical personnel should understand the medications and attributes of patients for an accurate assessment of their risk factors for falling and thus implement fall prevention measures and health education to reduce falls.

Identification, validation and biological characterisation of novel glioblastoma tumour microenvironment subtypes: implications for precision immunotherapy.

BACKGROUND: New precision medicine therapies are urgently required for glioblastoma (GBM). However, to date, efforts to subtype patients based on molecular profiles have failed to direct treatment strategies. We hypothesised that interrogation of the GBM tumour microenvironment (TME) and identification of novel TME-specific subtypes could inform new precision immunotherapy treatment strategies. MATERIALS AND METHODS: A refined and validated microenvironment cell population (MCP) counter method was applied to >800 GBM patient tumours (GBM-MCP-counter). Specifically, partition around medoids (PAM) clustering of GBM-MCP-counter scores in the GLIOTRAIN discovery cohort identified three novel patient clusters, uniquely characterised by TME composition, functional orientation markers and immune checkpoint proteins. Validation was carried out in three independent GBM-RNA-seq datasets. Neoantigen, mutational and gene ontology analysis identified mutations and uniquely altered pathways across subtypes. The longitudinal Glioma Longitudinal AnalySiS (GLASS) cohort and three immunotherapy clinical trial cohorts [treatment with neoadjuvant/adjuvant anti-programmed cell death protein 1 (PD-1) or PSVRIPO] were further interrogated to assess subtype alterations between primary and recurrent tumours and to assess the utility of TME classifiers as immunotherapy biomarkers. RESULTS: TMEHigh tumours (30%) displayed elevated lymphocyte, myeloid cell immune checkpoint, programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 transcripts. TMEHigh/mesenchymal+ patients featured tertiary lymphoid structures. TMEMed (46%) tumours were enriched for endothelial cell gene expression profiles and displayed heterogeneous immune populations. TMELow (24%) tumours were manifest as an 'immune-desert' group. TME subtype transitions upon recurrence were identified in the longitudinal GLASS cohort. Assessment of GBM immunotherapy trial datasets revealed that TMEHigh patients receiving neoadjuvant anti-PD-1 had significantly increased overall survival (P = 0.04). Moreover, TMEHigh patients treated with adjuvant anti-PD-1 or oncolytic virus (PVSRIPO) showed a trend towards improved survival. CONCLUSIONS: We have established a novel TME-based classification system for application in intracranial malignancies. TME subtypes represent canonical 'termini a quo' (starting points) to support an improved precision immunotherapy treatment approach.

Breakup of the proton halo nucleus 8B near barrier energies.

The dynamics of a nuclear open quantum system could be revealed in the correlations between the breakup fragments of halo nuclei. The breakup mechanism of a proton halo nuclear system is of particular interest as the Coulomb polarization may play an important role, which, however, remains an open question. Here we use a highly efficient silicon detector array and measure the correlations between the breakup fragments of 8B incident on 120Sn at near-barrier energies. The energy and angular correlations can be explained by a fully quantum mechanical method based on the state-of-the-art continuum discretized coupled channel calculations. The results indicate that, compared to the neutron halo nucleus 6He, 8B presents distinctive reaction dynamics: the dominance of the elastic breakup. This breakup occurs mainly via the short-lived continuum states, almost exhausts the 7Be yield, indicating the effect of Coulomb polarization on the proton halo state. The correlation information reveals that the prompt breakup mechanism dominates, occurring predominantly on the outgoing trajectory. We also show that, as a large environment, the continuum of 8B breakup may not significantly influence elastic scattering and complete fusion.

[Comparative study of gap balancing and measured resection technique in patients receiving staged bilateral total knee arthroplasty].

Objective: To compare the clinical outcomes of staged total knee arthroplasty (TKA) performed on both knees in the same patient using gap balancing (GB) and measured resection (MR) techniques, respectively. Methods: The clinical data of 57 patients undergoing bilateral staged TKA at the Xi'an Jiaotong University Affiliated Honghui Hospital from July 2018 to January 2020 were analyzed. Using the random number table, MR or GB technique was selected when patients underwent primary TKA, and contralateral procedure was done with another technique. The procedures were performed by one chief surgeon, and the same prosthesis was chosen for all the procedures. The two osteotomy techniques for TKA were compared in terms of surgical status, radiographic data, functional recovery and satisfaction rate. Results: Total of 57 patients, including 16 males and 41 females, were included in the study with a mean age of (68.5±4.6) years (59-79 years) at primary TKA. All patients were followed up for (29.6±4.5) months (22-39 months). The interval between the two procedures was (4.7±3.0) months (0.5-12.0 months). Postoperative drainage was less in the GB side when compared with that in the MR side [(93.6±22.2) ml vs (109.9±36.9) ml, P=0.003]. At the 1-month postoperative follow-up, the visual analogue scale (VAS) of pain was lower on the GB side (3.0±0.8) than on the MR side (3.5±1.2), the range of motion (ROM) was higher on the GB side (105.7°±8.2° vs 100.2°±7.5°), the Knee Society Score (KSS) was higher on the GB side (78.5±5.4 vs 74.2±6.3), and the Western Ontario and McMaster University (WOMAC) score was lower on the GB side (35.4±5.5 vs 38.0±6.3), there were significant differences in the up-mentioned indexes between the two groups (all P<0.05). However, the repeated-measures analysis of variance indicated that there was no significant difference in VAS score, ROM, KSS score and WOMAC score between the two techniques (all P>0.05). The satisfactory rate of GB technique was 84.2%(48/57), ant it was 86.0%(49/57) with MR technique (P=0.446). There was also no significant difference between the two techniques in terms of complications (P=0.754). Conclusion: Both the GB and MR technique result in good knee function with similar clinical outcomes in patients receiving TKA in both knees for osteoarthritis without significant deformity.

Influence of taper design and loading on taper micromotion.

Debris originating at the bore-trunnion interface of modular total hip replacements has been identified as one of the causes of hip replacements failure. Friction associated with fretting and corrosion represents a potential generator of these harmful particles. Understanding the motions at the interface will help to interpret the different damage patterns found in retrieval studies and minimize the risk of fluid ingress/egress into the taper interface. Accordingly, the present study is designed to characterise the nature of the relative motions generated at the bore-trunnion interface of different taper designs during typical loading profiles. 3D Finite Element (FE) models of a CoCr femoral head assembled onto a Ti alloy trunnion were generated and variables including taper clearance, deviation from roundness, assembly force and loading conditions were introduced. Resulting micromotions relative to the trunnion surface, separation and contact area of the bore-trunnion interface were shown to be affected by both taper design and types of activities. Results indicated that, in some cases, the largest component of motion corresponded to that developed normal to the trunnion surface. Furthermore, out of roundness as small as 6 µm across the diameter, in particular orientations, significantly changed the contact mechanics and magnitude of relative motions. From the resulting parameters at the bore-trunnion interface, a pump type of motion was identified during walking, jogging and stairs up activities. The components of relative motions at the bore-trunnion interface were found to be different regardless of the resultant magnitude of the relative motions. The findings highlight the importance of high-quality manufacturing processes as small changes in the trunnion component will significantly affect the clinical performance of this common type of modular approach in total hip replacements.

Dabrafenib plus trametinib in patients with BRAF V600E-mutant anaplastic thyroid cancer: updated analysis from the phase II ROAR basket study.

BACKGROUND: Combined therapy with dabrafenib plus trametinib was approved in several countries for treatment of BRAF V600E-mutant anaplastic thyroid cancer (ATC) based on an earlier interim analysis of 23 response-assessable patients in the ATC cohort of the phase II Rare Oncology Agnostic Research (ROAR) basket study. We report an updated analysis describing the efficacy and safety of dabrafenib plus trametinib in the full ROAR ATC cohort of 36 patients with ∼4 years of additional study follow-up. PATIENTS AND METHODS: ROAR (NCT02034110) is an open-label, nonrandomized, phase II basket study evaluating dabrafenib plus trametinib in BRAF V600E-mutant rare cancers. The ATC cohort comprised 36 patients with unresectable or metastatic ATC who received dabrafenib 150 mg twice daily plus trametinib 2 mg once daily orally until disease progression, unacceptable toxicity, or death. The primary endpoint was investigator-assessed overall response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1. Secondary endpoints were duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. RESULTS: At data cutoff (14 September 2020), median follow-up was 11.1 months (range, 0.9-76.6 months). The investigator-assessed ORR was 56% (95% confidence interval, 38.1% to 72.1%), including three complete responses; the 12-month DOR rate was 50%. Median PFS and OS were 6.7 and 14.5 months, respectively. The respective 12-month PFS and OS rates were 43.2% and 51.7%, and the 24-month OS rate was 31.5%. No new safety signals were identified with additional follow-up, and adverse events were consistent with the established tolerability of dabrafenib plus trametinib. CONCLUSIONS: These updated results confirm the substantial clinical benefit and manageable toxicity of dabrafenib plus trametinib in BRAF V600E-mutant ATC. Dabrafenib plus trametinib notably improved long-term survival and represents a meaningful treatment option for this rare, aggressive cancer.

Global Burden and Inequality of Dental Caries, 1990 to 2019.

Previous studies on the global burden of caries primarily focused on simple descriptive statistics. We aimed to characterize the burden, trends, and inequalities of untreated caries of permanent and deciduous teeth from 1990 to 2019 at the global, regional, and national levels through an array of analytic approaches. Estimates of caries burden were extracted from the Global Burden of Disease Study 2019. Decomposition analysis was performed to examine the contribution of demographic and epidemiologic factors to the evolving number of prevalent caries cases. In portfolio analysis, the caries epidemiologic profile of each country was categorized by terciles of age-standardized prevalence in 2019 and average annual percentage change from 1990 to 2019. Sociodemographic attribution analysis was performed to reveal the scale of inequality in burden of caries. Age-standardized prevalence of caries in permanent and deciduous teeth decreased 3.6% (95% uncertainty interval, 2.6% to 4.5%) and 3.0% (1.3% to 4.9%), respectively. Population growth was the key driver of the changes in the number of caries cases, especially in sub-Saharan Africa (percentage contribution: 126.6%, permanent teeth; 103.0%, deciduous teeth). Caries prevalence in the permanent dentition was lower in more developed countries, whereas a reverse trend was noted in the deciduous dentition, except for the highest sociodemographic quintile where caries prevalence was the lowest. Globally, 64.6 million (95% CI, 64.4 to 64.9 million) and 62.9 million (62.8 to 63.1 million) prevalent cases of caries in permanent and deciduous teeth were attributable to sociodemographic inequality in 2019. This amounted to 3.2% (3.2% to 3.2%) and 12.1% (12.1% to 12.1%) of the global number of prevalent cases of caries in permanent and deciduous teeth. Burden of dental caries remains a global public health challenge. A systemwide reform of the global oral health care system is needed to tackle the causes of the burden and inequality of dental caries.

One-Pot Synthesis of Chlorophyll-Assisted Exfoliated MoS2/WS2 Heterostructures via Liquid-Phase Exfoliation Method for Photocatalytic Hydrogen Production.

Developing strategies for producing hydrogen economically and in greener ways is still an unaccomplished goal. Photoelectrochemical (PEC) water splitting using photoelectrodes under neutral electrolyte conditions provides possibly one of the greenest routes to produce hydrogen. Here, we demonstrate that chlorophyll extracts can be used as an efficient exfoliant to exfoliate bulk MoS2 and WS2 to form a thin layer of a MoS2/WS2 heterostructure. Thin films of solution-processed MoS2 and WS2 nanosheets display photocurrent densities of -1 and -5 mA/cm2, respectively, and hydrogen evolution under simulated solar irradiation. The exfoliated WS2 is significantly more efficient than the exfoliated MoS2; however, the MoS2/WS2 heterostructure results in a 2500% increase in photocurrent densities compared to the individual constituents and over 12 h of PEC durability under a neutral electrolyte. Surprisingly, in real seawater, the MoS2/WS2 heterostructure exhibits stable hydrogen production after solar illumination for 12 h. The synthesis method showed, for the first time, how the MoS2/WS2 heterostructure can be used to produce hydrogen effectively. Our findings highlight the prospects for this heterostructure, which could be coupled with various processes towards improving PEC efficiency and applications.

Yak milk-derived exosomes alleviate lipopolysaccharide-induced intestinal inflammation by inhibiting PI3K/AKT/C3 pathway activation.

Intestinal epithelial cells (IEC) are important parts of the mucosal barrier, whose function can be impaired upon various injury factors such as lipopolysaccharide. Although food-derived exosomes are preventable against intestinal barrier injuries, there have been few studies on the effect of yak milk-derived exosomes and the underlying mechanism that remains poorly understood. This study aimed to characterize the effect of exosomal proteins derived from yak and cow milk on the barrier function of IEC-6 treated with lipopolysaccharide and the relevant mechanism involved. Proteomics study revealed 392 differentially expressed proteins, with 58 higher expressed and 334 lower expressed in yak milk-derived exosomes than those in cow exosomes. Additionally, the top 20 proteins with a relatively consistent higher expression in yak milk exosomes than cow milk exosomes were identified. Protein CD46 was found to be a regulator for alleviating inflammatory injury of IEC-6. In vitro assay of the role of yak milk exosomes on survival of IEC-6 in inflammation by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide assay confirmed the effectiveness of yak milk exosomes to increase IEC-6 survival up to 18% for 12 h compared with cow milk exosomes (up to 12%), indicating a therapeutic effect of yak milk exosomes in the prevention of intestinal inflammation. Furthermore, yak and cow milk exosomes were shown to activate the PI3K/AKT/C3 signaling pathway, thus promoting IEC-6 survival. Our findings demonstrated an important relationship between yak and cow milk exosomes and intestinal inflammation, facilitating further understanding of the mechanisms of inflammation-driven epithelial homeostasis. Interestingly, compared with cow milk exosomes, yak milk exosomes activated the PI3K/AKT/C3 signaling pathway more to lower the incidence and severity of intestine inflammation, which might represent a potential innovative therapeutic option for intestinal inflammation.

Titanium dioxide nanotubes promote M2 polarization by inhibiting macrophage glycolysis and ultimately accelerate endothelialization.

Titanium has been widely used in prosthetic valves, but they are associated with serious defects in titanium-based prosthetic valves, such as thrombosis, calcification, and decay. Therefore, it is very important to biofunctionalize titanium-based valves to reduce inflammation and accelerate endothelialization of stents and antithrombosis. The titanium dioxide nanotubes were prepared from pure titanium (Ti) by anodic oxidation method in this study. The effects of titanium dioxide nanotubes on the metabolism of macrophages and the inflammatory reaction as implants were studied in vitro. The polarization state of macrophages and the ability to accelerate endothelialization were analyzed. The results demonstrated that titanium nanotubes promote M2 polarization of macrophages by inhibiting glycolysis and activating the Adenosine monophosphate-activated protein kinase (AMPK) signaling pathway. In general, biofunctionalization titanium with nanotube could inhibit macrophage glycolysis, reduce inflammatory factor release and promote M2 polarization by activating the AMPK signaling pathway. And endothelialization was accelerated in vitro. Our result demonstrated that titanium nanotube could act as a potential approach to biofunctionlize titanium-based prosthetic valves for endothelialization.

Osteogenic effects of the peptide fraction derived from pepsin-hydrolyzed bovine lactoferrin.

Osteoporosis is a common disease that frequently occurs in the older population, particularly in postmenopausal women. It severely compromises the health of the older population, and the drugs commonly used to treat osteoporosis have a variety of adverse effects. Lactoferrin (LF) is a protein present in milk that has recently been found to exhibit osteogenic activity. Lactoferrin is nontoxic and harmless, suggesting that it may have excellent biocompatibility and tolerability after human consumption. Oral consumption of LF in an ovariectomized rat model has been found to ameliorate osteoporosis. However, the mechanism underlying this effect remains to be clarified. In this study, bovine LF (bLF) was first hydrolyzed by pepsin for 1 h, and the hydrolyzed mixture was freeze-dried and collected. The hydrolyzed mixture was then separated into 5 components (E1-E5), of which E3 had the greatest effect in promoting proliferation of osteoblasts (MC3T3-E1). Component E3 was further isolated into 21 components with preparative reversed phase HPLC, and the E3-15 component had maximal bioactivity. With HPLC-mass spectrometry and peptide sequencing, E3-15 was identified to contain amino acids 97 to 208 from the bLF N terminus. Then, E3-15 was divided into 6 different peptide segments (P1-P6), and the corresponding segments were generated by solid-phase synthesis. Only the P1 peptide (amino acids 97-122 from the N terminus of bLF) significantly promoted osteoblast proliferation. The bioactivity of P1 toward osteoblast cells and alkaline phosphatase activity were tested as a function of P1 concentration, and a nonlinear effect was observed.

Yak milk-derived exosomal microRNAs regulate intestinal epithelial cells on proliferation in hypoxic environment.

Intestinal epithelial cells (IEC) act as an important intestinal barrier whose function can be impaired upon induction by hypoxia. Although intestinal barrier injuries are preventable by milk-derived exosomal microRNAs (miRNAs), the underlying mechanism remains poorly understood. This study aimed to characterize the effect of yak and cow milk-derived exosomal miRNA on the barrier function of IEC-6 under hypoxic conditions, and explore the mechanism of yak milk exosomal miRNA to relieve the hypoxia stress. First, by Illumina HiSeq 2500 (Illumina Inc., San Diego, CA) sequencing, the miRNA expression was systematically screened, and differential expression of 130 miRNAs was identified with 51 being upregulated and 79 downregulated in yak and cow milk-derived exosomes. Furthermore, the top 20 miRNAs that had a relatively consistent high expression in yak milk exosome were identified, and bta-miR-34a was found to be an effective regulator for alleviating hypoxic injury of IEC-6. In vitro assay of the role of bta-miR-34a on survival of IEC-6 in hypoxia by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) confirmed its effectiveness to significantly increase IEC-6 survival up to 13% for 12 h, and up to 9.5% for 24 h. Investigation on the regulatory relationship between bta-miRNA-34a and the hypoxia-inducible factor/apoptosis signaling pathway provided insights into the possible mechanisms by which bta-miR-34a activated the hypoxia-inducible factor and apoptosis signaling pathway, thus promoting IEC-6 survival. The results of this study suggest an important relationship between miRNA expression and intestine barrier integrity, which facilitated further understanding of the physiological function of yak and cow milk exosomal miRNAs, as well as mechanisms of hypoxia-driven epithelial homeostasis.

Identification of reproduction-related genes and pathways in the Culter alburnus H-P-G axis and characterization of their expression differences in malformed and normal gynogenetic ovaries.

This study applied RNA-seq technology to discover reproduction-related genes and pathways in female topmouth culter brain (including pituitary) and ovarian tissues. In functional analysis, 2479 and 2605 unigenes in the brain and ovary tissue were assigned to the "reproductive process" subcategory in addition to the 2660 and 2845 unigenes assigned to the "reproduction" subcategory. Twenty-three complete cDNA sequences were identified through the different gene expression (DGE) approach from five reproduction-related pathways (MAPK signaling pathway, neuroactive ligand-receptor interaction pathway, gonadotropin-releasing hormone signaling pathway, oocyte meiosis pathway, and steroid biosynthesis pathway). The expression levels of 16 candidate genes using qPCR in this study were in accordance with the results of transcriptome analysis. In addition, the expression levels of the FSH, 3ß-HSD, PGR, and NPYR genes in malformed gynogenetic ovaries were considerably low, which was consistent with the progress of oocytogenesis in the ovaries of topmouth culter. The high expression of these four genes in the ovaries of normal topmouth culter suggested they might involve in the preparation for the shift of oogenesis to ovulation. Hence, our work identified a set of annotated gene products that are candidate factors affecting reproduction in the topmouth culter H-P-G axis. These results could be essential for further research in functional genomics and genetic editing for topmouth culter reproduction.

Large Isospin Asymmetry in

ß-delayed one-proton emissions of ^{22}Si, the lightest nucleus with an isospin projection T_{z}=-3, are studied with a silicon array surrounded by high-purity germanium detectors. Properties of ß-decay branches and the reduced transition probabilities for the transitions to the low-lying states of ^{22}Al are determined. Compared to the mirror ß decay of ^{22}O, the largest value of mirror asymmetry in low-lying states by far, with δ=209(96), is found in the transition to the first 1^{+} excited state. Shell-model calculation with isospin-nonconserving forces, including the T=1, J=2, 3 interaction related to the s_{1/2} orbit that introduces explicitly the isospin-symmetry breaking force and describes the loosely bound nature of the wave functions of the s_{1/2} orbit, can reproduce the observed data well and consistently explain the observation that a large δ value occurs for the first but not for the second 1^{+} excited state of ^{22}Al. Our results, while supporting the proton-halo structure in ^{22}Al, might provide another means to identify halo nuclei.

Metallic Glacial Glass Formation by a First-Order Liquid-Liquid Transition.

The glacial phase, with an apparently glassy structure, can be formed by a first-order transition in some molecular-glass-forming supercooled liquids. Here we report the formation of metallic glacial glass (MGG) from the precursor of a rare-earth-element-based metallic glass via the first-order phase transition in its supercooled liquid. The excellent glass-forming ability of the precursor ensures the MGG to be successfully fabricated into bulk samples (with a minimal critical diameter exceeding 3 mm). Distinct enthalpy, structure, and property changes are detected between MGG and metallic glass, and the reversed "melting-like" transition from the glacial phase to the supercooled liquid is observed in fast differential scanning calorimetry. The kinetics of MGG formation is reflected by a continuous heating transformation diagram, with the phase transition pathways measured at different heating rates taken into account. The finding supports the scenario of liquid-liquid transition in metallic-glass-forming liquids.

Meta-analysis of prophylactic cranial irradiation or not in treatment of extensive-stage small-cell lung cancer: The dilemma remains.

PURPOSE: The role of prophylactic cranial irradiation (PCI) in treatment of extensive-stage small-cell lung cancer (SCLC) is controversial. The aim of this study was to systematically evaluate the efficacy and safety of using PCI in the treatment of extensive-stage SCLC. In the present study, we examined whether PCI was essential for the optimal treatment of extensive-disease small-cell lung cancer. MATERIAL AND METHODS: We searched the PubMed, Embase, Medline, and China National Knowledge Infrastructure databases to identify articles that assessed the efficacy of PCI in treating extensive-stage small-cell lung cancer patients. RESULTS: We identified 8 studies that involved a total of 982 patients who received PCI (PCI group) and a total of 4509 patients who did not receive PCI (control group). The results showed that PCI significantly improved the 1-year overall survival rate (HR=1.50; 95% CI: 1.23-1.82; I2=67%; P<0.0001) and reduced the incidence of brain metastasis (HR=0.46; 95% CI: 0.37-0.58; I2=6%; P<0.00001). CONCLUSION: PCI improves the 1-year overall survival rate and reduces the risk of brain metastasis in patients with extensive-stage SCLC.