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Topology optimization has become an effective tool for least-weight and performance design, especially in aeronautics and aerospace engineering. The purpose of this paper is to survey recent advances of topology optimization techniques applied in aircraft and aerospace structures design. This paper firstly reviews several existing applications: (1) standard material layout design for airframe structures, (2) layout design of stiffener ribs for aircraft panels, (3) multi-component layout design for aerospace structural systems, (4) multi-fasteners design for assembled aircraft structures. Secondly, potential applications of topology optimization in dynamic responses design, shape preserving design, smart structures design, structural features design and additive manufacturing are introduced to provide a forward-looking perspective.

Anticancer activities of flavonoids derived from Tephroseris kirilowii (Turcz.) Holub. were evaluated in human cancer cells. We isolated and identified, for the first time, eight flavonoids from T . kirilowii and found that three of them (IH: isorhamnetin, GN: genkwanin, and Aca: acacetin) inhibited cell proliferation in a variety of human cancer cell lines. These active flavonoids caused cell cycle arrest at G2/M phase and induced apoptosis and autophagy in human breast cancer cells. Molecular docking revealed that these flavonoids dock in the ATP binding pocket of PI3Kγ. Importantly, treatment with these flavonoids decreased the levels of PI3Kγ-p110, phospho-PI3K, phospho-AKT, phospho-mTOR, phospho-p70S6K, and phospho-ULK. Pretreatment with PI3Kγ specific inhibitor AS605240 potentiated flavonoids-mediated inactivation of AKT, mTOR, p70S6K, ULK, and apoptosis. Taken together, these findings represent a novel mechanism by which downregulation of PI3Kγ-p110 and consequent interruption of PI3K/AKT/mTOR/p70S6K/ULK signaling pathway might play a critical functional role in these flavonoids-induced cell cycle arrest at G2/M phase, apoptosis, and autophagy. Our studies provide novel insights into the anticancer activities of selected flavonoids and their potential uses in anticancer therapy.

ObjectivesTo analyse the prevalence and determinants of turnover intention (TI) among primary health workers (PHWs) in China to provide evidence for improving retention measures.DesignSystemic review and meta-analysis.Data sourcesFour English-language databases (PubMed, EMBASE, Cochrane Library, PsycINFO) and three Chinese databases (CNKI, CSPD, CBM) were searched up to October 2019.Eligibility criteriaEligible studies were observational or descriptive studies conducted in mainland China. The prevalence of TI among health workers and related factors had to be explicitly reported in each included study.Data extraction and synthesisData were extracted by one author and reviewed independently by two other authors. For each factor analysed by a meta-analysis, the factor was required to be the same across different studies, and at least three studies had to include it. The quality of studies was assessed using the Newcastle–Ottawa Scale and heterogeneity was evaluated using the I2 statistic.ResultsWe identified 16 cross-sectional studies investigating a total of 37 672 PHWs. The prevalence of TI was 30.4%. Subgroup analysis revealed that the highest prevalence was observed in the community primary healthcare institutions and the eastern provinces of China. Meta-analyses indicated that 21 factors were significantly associated with TI, including demographic factors (gender, age, education, marital status), job characteristic factors (title, work seniority, remuneration, social status, organisational affiliation, work stress) and job satisfaction factors (learning and training opportunity, interpersonal relationship, work condition and environment, and so on).ConclusionThis study highlights the problem of TI among PHWs in China. Efforts should be made to improve conditions in both work-related areas and areas outside of work. Policymakers should continue to improve reward systems, the construction of infrastructure and promotion systems, and pay more attention to PHWs’ lives outside of work and meet their living needs.

MicroRNA‐24‐3p (miR‐24‐3p) has been implicated as a key promoter of chemotherapy resistance in numerous cancers. Meanwhile, cancer‐associated fibroblasts (CAFs) can secret exosomes to transfer miRNAs, which mediate tumour development. However, little is known regarding the molecular mechanism of CAF‐derived exosomal miR‐24‐3p in colon cancer (CC). Hence, this study intended to characterize the functional relevance of CAF‐derived exosomal miR‐24‐3p in CC cell resistance to methotrexate (MTX). We identified differentially expressed HEPH, CDX2 and miR‐24‐3p in CC through bioinformatics analyses, and validated their expression in CC tissues and cells. The relationship among HEPH, CDX2 and miR‐24‐3p was verified using ChIP and dual‐luciferase reporter gene assays. Exosomes were isolated from miR‐24‐3p inhibitor–treated CAFs (CAFs‐exo/miR‐24‐3p inhibitor), which were used in combination with gain‐of‐function and loss‐of‐function experiments and MTX treatment. CCK‐8, flow cytometry and colony formation assays were conducted to determine cell viability, apoptosis and colony formation, respectively. Based on the findings, CC tissues and cells presented with high expression of miR‐24‐3p and low expression of HEPH and CDX2. CDX2 was a target gene of miR‐24‐3p and could up‐regulate HEPH. Under MTX treatment, overexpressed CDX2 or HEPH and down‐regulated miR‐24‐3p reduced cell viability and colony formation and elevated cell apoptosis. Furthermore, miR‐24‐3p was transferred into CC cells via CAF‐derived exosomes. CAF‐derived exosomal miR‐24‐3p inhibitor diminished cell viability and colony formation and increased cell apoptosis in vitro and inhibited tumour growth in vivo under MTX treatment. Altogether, CAF‐derived exosomal miR‐24‐3p accelerated resistance of CC cells to MTX by down‐regulating CDX2/HEPH axis.

Objective The present study conducted a meta‐analysis to synthesize the associations between sexual minority stress and relationship satisfaction, as well as to examine actor and partner effects. Background Sexual minority individuals in same‐sex couples experience various distinct and chronic stressors related to their stigmatized identities and romantic relationships, and these stressors negatively impact relationship satisfaction. Although there have been two meta‐analyses that sought to examine these influences, some fundamental questions remain unanswered. In particular, the roles of dyadic processes and different types of sexual minority stressors remain unclear. Method A comprehensive search identified 67 studies with 147 effect sizes representing 24,542 individuals. Results The results revealed a significant small association (r = −.100 to −.188) between sexual minority stressors and relationship satisfaction. Internalized stressors were more strongly associated with relationship satisfaction than other types of sexual minority stressors (e.g., prejudice events and concealment). Dyadic analyses demonstrated a significant actor effect of concealment, experiencing prejudice events, and internalized stressors on relationship satisfaction, with the largest effect size for concealment effects. Conclusion These findings suggest that sexual minority stressors could potentially contribute to same‐sex relational problems. They also underscore the importance of interdependence (both partners' responses as well as their interaction with sexual minority stressors). This understanding may be instrumental in shaping prevention strategies. Implications The meta‐analysis emphasizes the nuanced impact of sexual minority stressors on same‐sex relationship satisfaction, highlighting the importance of targeted interventions. It underscores the role of dyadic processes, emphasizing the significance of both partners' responses and interactions with stressors in developing effective prevention strategies for healthier same‐sex relationships.

Background Women's cancers, represented by breast and gynecologic cancers, are emerging as a significant threat to women's health, while previous studies paid little attention to the spatial distribution of women's cancers. This study aims to conduct a spatio-temporal epidemiology analysis on breast, cervical and ovarian cancers in China, thus visualizing and comparing their epidemiologic trends and spatio-temporal changing patterns. Methods Data on the incidence and mortality of women’s cancers between January 2010 and December 2015 were obtained from the National Cancer Registry Annual Report. Linear tests and bar charts were used to visualize and compare the epidemiologic trends. Two complementary spatial statistics (Moran’s I statistics and Kulldorff’s space–time scan statistics) were adopted to identify the spatial–temporal clusters. Results The results showed that the incidence and mortality of breast cancer displayed slow upward trends, while that of cervical cancer increase dramatically, and the mortality of ovarian cancer also showed a fast increasing trend. Significant differences were detected in incidence and mortality of breast, cervical and ovarian cancer across east, central and west China. The average incidence of breast cancer displayed a high-high cluster feature in part of north and east China, and the opposite traits occurred in southwest China. In the meantime, the average incidence and mortality of cervical cancer in central China revealed a high-high cluster feature, and that of ovarian cancer in northern China displayed a high-high cluster feature. Besides, the anomalous clusters were also detected based on the space–time scan statistics. Conclusion Regional differences were detected in the distribution of women’s cancers in China. An effective response requires a package of coordinated actions that vary across localities regarding the spatio-temporal epidemics and local conditions.

Background Since 2009, Morocco has been implementing the Maternal Death Surveillance System (MDSS). The results obtained indicate significant regional variations in terms of implementation stage, completeness of maternal death reporting, and information use for action. The objective of this research is to better understand the contextual factors involved in the implementation process and use of MDSS, with a focus on the facilitators and barriers, as experienced by stakeholders in health regions.  Methods Evaluation research was conducted in 2017 based on a descriptive qualitative study using semi-structured in-depth interviews, in four out of the twelve health regions of Morocco. A total of thirty-one in-depth interviews were held with members of regional committees of maternal death reviews (RC-MDR) and other key informant staff. Interviews focused on participants’ views and their experiences with the MDSS since the introduction in 2009. We conducted thematic analysis relied on inductive and deductive approaches. Applying the Consolidated Framework for Implementation Research guided data analysis and reporting findings.  Findings Engaging leadership at all health system levels, regular training of district and regional MDSS coordinators and supportive supervision at a national level were the most important MDSS implementation facilitators. Reported barriers were essentially related to the review system: Irregular review meetings, blame culture, high turn-over of RC-MDR members, lack of analytical capacity to inform the review process and formulate recommendations, finally limited accountability for recommendation follow-up. While financial incentives boosted MDSS adoption, they were nonetheless a substantial barrier to its sustainability. Conclusions The MDSS is a complex process that requires taking numerous steps, including the commitment of multiple stakeholders with varying roles as well as information sharing across health system levels. Contextual factors that influence MDSS implementation at the sub-national level are to be considered. Horizontal and vertical communication about MDSS goals and feedback is crucial to strengthen stakeholders’ commitment, hence improving quality and use of MDSS. Furthermore, health regions should place emphasis on making high-quality recommendations in partnerships between the regional management teams, RC-MDR members and external stakeholders.

Cancer cells preferentially metabolize glucose through aerobic glycolysis. This phenomenon, known as the Warburg effect, is an anomalous characteristic of glucose metabolism in cancer cells. Chronic inflammation is a key promoting factor of tumourigenesis. It remains, however, largely unexplored whether and how pro‐tumourigenic inflammation regulates glucose metabolism in cancer cells. Here, we show that pro‐inflammatory cytokines promote glycolysis in breast cancer cells, and that the inflammation‐induced miR‐155 functions as an important mediator in this process. We further show that miR‐155 acts to upregulate hexokinase 2 ( hk2 ), through two distinct mechanisms. First, miR‐155 promotes hk2 transcription by activation of signal transducer and activator of transcription 3 (STAT3), a transcriptional activator for hk2 . Second, via targeting C / EBP β (a transcriptional activator for mir‐143 ), miR‐155 represses mir‐143 , a negative regulator of hk2 , thus resulting in upregulation of hk2 expression at the post‐transcriptional level. The miR‐155‐mediated hk2 upregulation also appears to operate in other types of cancer cells examined. We suggest that the miR‐155/miR‐143/HK2 axis may represent a common mechanism linking inflammation to the altered metabolism in cancer cells. Molecular analyses in this study identify inflammation‐induced miRNA regulation of central glycolytic enzymes. Focussing on hexokinase‐2 as major target therapeutically exploitable consequences for cell proliferation, migration, and metastasis are functionally established.

Mode-division multiplexing (MDM) is a promising technology for increasing the data-carrying capacity of a single few-mode optical fiber. The flexible mode manipulation would be highly desired in a robust MDM network. Recently, orbital angular momentum (OAM) modes have received wide attention as a new spatial mode basis. In this paper, we firstly proposed a long period fiber grating (LPFG) system to realize mode conversions between the higher order LP core modes in four-mode fiber. Based on the proposed system, we, for the first time, demonstrate the controllable all-fiber generation and conversion of the higher order LP core modes to the first and second order circularly polarized OAM beams with all the combinations of spin and OAM. Therefore, the proposed LPFG system can be potentially used as a controllable higher order OAM beam switch and a physical layer of the translating protocol from the conventional LP modes communication to the OAM modes communication in the future mode carrier telecommunication system and light calculation protocols.

This article develops a new method to mitigate chatter vibrations in the thin-wall milling of the structures with half-opened side walls through designing a supplementary device, which can provide double-side support to the weakly rigid positions between cutter and workpiece. It aims to improve the stiffness and damping responses of the side walls without the need to consider the limitation of the workpiece’s geometrical configuration. That is, it is suitable for both the flat and the curved shapes. The typical structural characteristic of the device lies in that as the cutting continues, the supporting positions can be easily adjusted up and down along the axial direction to meet the instantaneous chatter mitigation requirement. Dynamic models of both the curved thin-wall milling process and the workpiece with the supplementary support device are derived by integrating the milling mechanics with the receptance coupling substructure analysis. The in-process modal parameters of the workpiece with the support device, i.e., natural frequency and modal shape, are calculated by comprehensively considering the removal of material and the influence of the supporting position change. Finally, a method that combines the derived models with the dynamic response of the spindle-tool system is used to predict the stability lobe diagrams (SLDs), with which chatter vibrations can be well avoided by reasonably selecting the cutting parameters. A series of thin-wall milling experiments are carried out on typical curved plates to validate the effectiveness of the designed support device together with the proposed methods for mitigating chatter vibrations.