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Background. To investigate the potential benefits of the auricular point acupressure on cerebrovascular function and stroke prevention among adults with high stroke risk. Methods. A randomized controlled study was performed in 105 adults at high risk for stroke between March and July 2021. Participants were randomly allocated (1 : 1) to receive either auricular point acupressure with basic lifestyle interventions (n = 53) or basic lifestyle interventions alone (n = 52) for 2 weeks. The primary outcome was the kinematic and dynamic indices of cerebrovascular function, as well as CVHP score at week 2, measured by the Doppler ultrasonography and pressure transducer on carotids. Results. Among the 105 randomized subjects, 86 finished the intervention plans. At week 2, the auricular point acupressure therapy with lifestyle intervention group had higher kinematic indices, cerebrovascular hemodynamic parameters score and lower dynamic indices than the lifestyle intervention group. Conclusions. Cerebrovascular function and cerebrovascular hemodynamic parameters score were greater improved among the participants undergoing auricular point acupressure combined with lifestyle interventions than lifestyle interventions alone. Hence, the auricular point acupressure can assist the stroke prevention. Trail Registration. This trial registered with ChiCTR2100041769 on https://www.chictr.org.cn/.

Posttranslational modifications expand the functions of immune-related proteins, especially during infections. The respiratory glycoprotein, hemocyanin, has been implicated in many other functions, but the role of phosphorylation modification in its functional diversity is not fully understood. In this study, we show that Penaeus vannamei hemocyanin (PvHMC) undergoes phosphorylation modification during bacterial infection. Dephosphorylation of PvHMC mediated by P. vannamei protein phosphatase 2A catalytic increases its in vitro antibacterial activity, whereas phosphorylation by P. vannamei casein kinase 2 catalytic subunit α decreases its oxygen-carrying capacity and attenuates its in vitro antibacterial activity. Mechanistically, we show that Thr517 is a critical phosphorylation modification site on PvHMC to modulate its functions, which when mutated attenuates the action of P. vannamei casein kinase 2 catalytic subunit α and P. vannamei protein phosphatase 2A catalytic, and hence abolishes the antibacterial activity of PvHMC. Our results reveal that phosphorylation of PvHMC modulates its antimicrobial functions in penaeid shrimp.

Objective. Hyperuricemia (HUA) is a common metabolic disease caused by disordered purine metabolism. We aim to reveal the mechanisms underlying the anti-HUA function of Simiao pill and provide therapeutic targets. Methods. Simiao pill-related targets were obtained using Herbal Ingredients’ Targets (HIT), Traditional Chinese Medicine Systems Pharmacology (TCMSP), and Traditional Chinese Medicine Integrated Database (TCMID). HUA-associated targets were retrieved from GeneCards, DisGeNET, and Therapeutic Targets Database (TTD). Protein-protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database, ggraph and igraph R packages. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed using ClusterProfiler. The top 10 core targets were identified through cytoHubba. Molecular docking was conducted using PyMOL and AutoDock high-performance liquid chromatograph (HPLC) analysis was performed to identify effective compounds of Simiao pill. Results. Simiao pill-HUA target network contained 80 targets. The key targets were mainly involved in inflammatory responses. Insulin (INS), tumor necrosis factor (TNF), interleukin-6 (IL6), interleukin 1 beta (IL1B), vascular endothelial growth factor A (VEGFA), leptin (LEP), signal transducer and activator of transcription 3 (STAT3), C-C motif chemokine ligand 2 (CCL2), interleukin-10 (IL10), and toll like receptor 4 (TLR4) were the top 10 targets in the PPI network. GO analysis demonstrated the main implication of the targets in molecular responses, production, and metabolism. KEGG analysis revealed that Simiao pill might mitigate HUA through advanced glycation end-product- (AGE-) receptor for AGE- (RAGE-) and hypoxia-inducible factor-1- (HIF-1-) associated pathways. IL1B, IL6, IL10, TLR4, and TNF were finally determined as the promising targets of Simiao pill treating HUA. Through molecular docking and HPLC analysis, luteolin, quercetin, rutaecarpine, baicalin, and atractylenolide I were the main active compounds. Conclusions. Simiao pill can mitigate HUA by restraining inflammation, mediating AGE-RAGE- and HIF-1-related pathways, and targeting IL1B, IL6, IL10, TLR4, and TNF.

Therapeutic nanoplatforms are widely used in the diagnosis and treatment of breast cancer due to the merits of enabling high soft-tissue resolution and the availability of numerous therapeutic nanoparticles. It is thus vital to develop multifunctional theranostic nanoparticles for the visualization and dynamic monitoring of tumor therapy. In this study, we designed a manganese-based and hypericin-loaded polyester dendrimer nanoparticle (MHD) for magnetic resonance imaging (MRI) and hypericin-based photodynamic therapy (PDT) enhancement. We found that MHD could greatly enhance MRI contrast with a longitudinal relaxivity of 5.8 mM

BackgroundThe total motherhood wage gap among U.S. college-educated women closed over the past two decades and was eliminated by the early 2010s. It is not clear, however, whether the COVID-19 pandemic reversed these trends.MethodsDrawing on nationally representative data from the 2000–2022 Current Population Surveys, this study uses linear regression models to estimate trends in the total motherhood wage gap among college-educated and non-college-educated women who work full-time.ResultsIn the decade leading up to the COVID-19 pandemic, college-educated women with children did not pay a substantial motherhood wage penalty, but their wages began to decline at the onset of the pandemic, and the decline accelerated over the following years. By the end of 2022, college-educated women paid a 6% wage penalty for motherhood. In contrast to college-educated women, women without a college degree did not experience a substantial change in the motherhood wage penalty during the pandemic.ContributionOur study provides new evidence indicating that by 2022, three years into the pandemic, college-educated mothers experienced the highest motherhood wage penalty since the turn of the 20th century, reversing two decades of progress for this group of women. This study reveals the longer-term career-related ramifications of the pandemic for college-educated mothers and highlights the precarity of mothers’ economic progress related to external shocks, especially those that disrupt childcare and educational systems.

In recent decades, the financial elite have seen their economic resources grow significantly, while the income and wealth of other households have stagnated. The financial elite includes couples who are super-rich (top one percent), rich (the 90th–99th percentile), and upper-middle class (the 80th–89th percentile). Gendered work–family arrangements in top economic groups may contribute to inequality—particularly to wealth accumulation among the elite—but relatively little is known about how these couples divide paid and unpaid work or the extent to which their arrangements differ from other couples. In this study, we uncover novel work and family patterns and trends in the most economically powerful families in the United States. We use the Survey of Consumer Finances (1989–2019) to compare the household division of labor across income and wealth groups and over time, with a focus on financial elites. We find stark contrasts between super-rich couples and other couples in the division of labor. Specifically, super-rich couples are much more likely than all other couples, including rich and upper-middle class couples, to have a traditional male breadwinner–female homemaker/caregiver arrangement. Importantly, the striking patterns of traditional arrangements in the top one percent have not changed in 30 years and, as we uncover, appear to be driven by a couple’s wealth rather than income. These findings suggest that work–family arrangements may be an integral component of economic and gender inequality.

The application of abundant and inexpensive fluorine feedstock sources to synthesize fluorinated compounds is an appealing yet underexplored strategy. Here, we report a photocatalytic radical hydrodifluoromethylation of unactivated alkenes with an inexpensive industrial chemical, chlorodifluoromethane (ClCF

Prior research has attributed the socio-economic disparity in COVID-19 infections to differences in degrees of exposure or economic resources. This study proposes beliefs about COVID-19 as a potential additional explanation. We conducted a nationally representative US survey with six measures of COVID-19 beliefs. Socio-economic status was measured through educational level. Compared with less-educated respondents, highly educated respondents treat COVID-19 more seriously, including believing in (1) face mask use, (2) asymptomatic transmission, (3) media non-exaggeration, (4) the necessity of stay-at-home orders, (5) a likelihood of themselves being infected with COVID-19 and (6) no protection of God against COVID-19. The educational gradient in COVID-19 beliefs was largely explained by differential levels of belief in science across education. Our findings suggest that encouraging public trust in science can potentially reduce the educational gradient in COVID-19 infections in the USA.

Purpose The leakage problem caused by machining error, assembly error, wearing and thermal deformation has been the main factor hindering the development of scroll compressor. This paper aims to investigate the lubrication characteristics of radial clearance and further optimize the radial clearance, which can reduce the leakage in the tangential direction of the working chamber. Design/methodology/approach This paper establishes a model of radial clearance oil film lubrication in scroll compressor. And, the method to solve the Reynolds and energy equations is presented, as well as the dimensionless and discretization by finite element difference method. To verify the established model, performance experiment of scroll compressor for electric vehicle air conditioning system is also carried out. Findings Based on the presented model, the temperature field and distribution of the oil film in the radial clearance are analyzed. And the influence of the structural parameter on the radial clearance is further discussed. The optimum radial clearance could be achieved at β = 40°–42°, where the orbiting scroll is in the state of rotary balance. And, the simulation results coincide well with the experimental results. Originality/value This work provides an effective model to evaluate the lubrication characteristics of radial clearance in scroll compressor, which can provide guidance for the design of scroll compressor.

Containment control is one of critical issues in multiagent systems (MASs). A recursive sliding-mode dynamic surface control (DSC) strategy with a nonlinear gain is addressed for the containment problem of uncertain MASs in strict-feedback form. Two factors, a recursive dynamic sliding-mode surface and a nonlinear gain function, are introduced to solve the contradiction between control accuracy and dynamic performance in the traditional DSC method. The function approximation technique, by radial basis function neural networks, is employed to compensate unknown dynamics. On the basis of the backstepping and graph theory, a full-state feedback containment control strategy is presented. Subsequently, we propose an output feedback containment control strategy via a state observer for individual followers. From the Lyapunov stability theorem, we construct an improvement Lyapunov function for the MAS, and it is proven that all followers converge to a convex hull formed by leaders for both full-state feedback and output feedback cases. Simulation examples are presented for verification of the effectiveness of the strategy.

Background: Chronic fatigue syndrome (CFS) is characterized by significant and persistent fatigue. Ginseng is a traditional anti-fatigue Chinese medicine with a long history in Asia, as demonstrated by clinical and experimental studies. Ginsenoside Rg1 is mainly derived from ginseng, and its anti-fatigue metabolic mechanism has not been thoroughly explored.Methods: We performed non-targeted metabolomics of rat serum using LC-MS and multivariate data analysis to identify potential biomarkers and metabolic pathways. In addition, we implemented network pharmacological analysis to reveal the potential target of ginsenoside Rg1 in CFS rats. The expression levels of target proteins were measured by PCR and Western blotting.Results: Metabolomics analysis confirmed metabolic disorders in the serum of CFS rats. Ginsenoside Rg1 can regulate metabolic pathways to reverse metabolic biases in CFS rats. We found a total of 34 biomarkers, including key markers Taurine and Mannose 6-phosphate. AKT1, VEGFA and EGFR were identified as anti-fatigue targets of ginsenoside Rg1 using network pharmacological analysis. Finally, biological analysis showed that ginsenoside Rg1 was able to down-regulate the expression of EGFR.Conclusion: Our results suggest ginsenoside Rg1 has an anti-fatigue effect, impacting the metabolism of Taurine and Mannose 6-phosphate through EGFR regulation. This demonstrates ginsenoside Rg1 is a promising alternative treatment for patients presenting with chronic fatigue syndrome.

This paper considers the stability and L2- $\text{L}_\infty $ control problem for It $\hat {o}$ stochastic systems with the sawtooth-like input delay. Compared with previously-known results on systems with the sawtooth-like input delay, a new auxiliary system is introduced to reduce the conservatism of the system. Besides, the influence of stochastic noises is investigated. For the delayed stochastic system without the disturbance, an LMI type mean-square asymptotical stability criterion is derived by using the Bessel-Legendre stochastic inequality and a modified finite-interval quadratic polynomial inequality. Then a linear feedback controller is proposed to realize the stability of the system with a prescribed L2- $\text{L}_\infty $ performance under the influence of disturbances, where the controller gain matrix is designed by introducing slack variables. To be pointed out that the augmented Lyapunov-Krasovskii functional (LKF) used in this paper is new, which is constructed by introducing an auxiliary system to increase the delay-dependent function terms in the discriminant. Finally, two numerical examples are given to show the validness and effectiveness of the theoretical results.

Aggregate figures unequivocally depict an increase in anti-Asian sentiment in the United States and other Western countries since the start of the COVID-19 pandemic, but there is limited understanding of the contexts under which Asians encounter discrimination. The authors examine how coethnic concentration shapes Asians’ experiences of discrimination across U.S. counties during COVID-19 and also assess whether county-level context (e.g., COVID-19 infection rates, unemployment rates) could help explain this relationship. The authors analyze the Understanding Coronavirus in America tracking survey, a nationally representative panel of American households, along with county-level contextual data. The authors find an n-shaped relationship between coethnic concentration and Asians’ perceived discrimination. This relationship is explained largely by county-level COVID-19 infection rates. Together, the context of medium Asian concentration and high COVID-19 cases created a particularly hostile environment for Asians during COVID-19.

Research on stigma and discrimination during COVID-19 has focused on racism and xenophobia in Western countries. In comparison, little research has considered stigma processes, discrimination, and their public health implications in non-Western contexts. This study draws on quantitative survey data (N = 7,942) and qualitative interview data (N = 50) to understand the emergence, experiences, and mental health implications of stigma and discrimination during China’s COVID-19 outbreak. Given China’s history of regionalism, we theorize and use a survey experiment to empirically assess region-based stigma: People who lived in Hubei (the hardest hit province) during the outbreak and those who were socially associated with Hubei were stigmatized. Furthermore, the COVID-19 outbreak created stigma around people labeled as patients by the state. These stigmatized groups reported greater perceived discrimination, which—as a stressor—led to psychological distress. Our interview data illuminated how the stigmatized groups perceived, experienced, and coped with discrimination and stigma.

Point clouds are characterized by irregularity and unstructuredness, which pose challenges in efficient data exploitation and discriminative feature extraction. In this paper, we present an unsupervised deep neural architecture called Flattening-Net to represent irregular 3D point clouds of arbitrary geometry and topology as a completely regular 2D point geometry image (PGI) structure, in which coordinates of spatial points are captured in colors of image pixels. \mr{Intuitively, Flattening-Net implicitly approximates a locally smooth 3D-to-2D surface flattening process while effectively preserving neighborhood consistency.} \mr{As a generic representation modality, PGI inherently encodes the intrinsic property of the underlying manifold structure and facilitates surface-style point feature aggregation.} To demonstrate its potential, we construct a unified learning framework directly operating on PGIs to achieve \mr{diverse types of high-level and low-level} downstream applications driven by specific task networks, including classification, segmentation, reconstruction, and upsampling. Extensive experiments demonstrate that our methods perform favorably against the current state-of-the-art competitors. We will make the code and data publicly available at https://github.com/keeganhk/Flattening-Net., Accepted to TPAMI

In discussing non-commutative spacetime, the generally studied $\theta$-Poincare model is inconsistent with bound states. In this Letter, we develop the formalism and study the phenomenology of another model $\mathcal{B}_{\chi \hat{n}}$ by the twisted permutation algebra and extend the Pauli Exclusion Principle(PEP) into non-commutative spacetime. The model also implies time quantization and can avoid UV/IR mixing. Applying it to atomic systems, we show that the model with newly induced phase factors can cause exotic transitions consisting of three electrons in the 1S orbit of atoms. The transition rate is derived, and the upper bound of non-commutative parameter $\chi$ is thus set by utilizing data from the low-energy and low-background experiments, where strongest constraint $\chi\leq4.05\times10^{-30}$ eV$^{-1}$ at 90\% C.L. is given by XENONnT, with the time quanta $\Delta t\sim 2.67\times 10^{-45} s$, equivalent to twenty times smaller than the Planck time., Comment: 6 pages, 4 figures

The addition of organic matter via green manure rotations in paddy rice has previously been proposed as a smart agricultural practice to maintain soil productivity and support environmental sustainability. However, to date, only a few studies have assessed quantitatively the impact of green manure application on the interactions between agronomic management practices, soil fertility, and crop production. In this study, 800 pairs of data from 108 studies, conducted in the Yangtze River agricultural region of China were assessed, and a meta-analysis was carried out to evaluate and quantify the effect of green manure application on rice yield and soil properties. Firstly, compared to a winter fallow system, amendment with green manure significantly increased paddy rice yield and soil organic carbon (SOC) by 8.1% and 8.4%, respectively. Secondly, analysis using a Random Forest model revealed that paddy rice type, green manure application rate and duration, mineral and organic N fertilizer rate, and initial SOC and pH were identified as the main drivers for paddy rice yield and SOC change. Finally, Marginal Benefit Analysis (MBA) revealed that green manure application rates for production in early rice of double cropping rice (ER) and single rice (SR) were approximately of 20 and 26 t ha-1 respectively. and further, for carbon sequestration, that the optimal rate was ~25 t ha-1. It should, however, be noted that green manure application to soils with already high SOC level might result in the soil becoming a net C source. The study supported the scientific and quantitative indicators for achieving the best benefits of paddy rice yield and SOC increase after green manure application.

ObjectivesTo establish visualised prediction models of low fertilisation rate (LFR) and total fertilisation failure (TFF) for patients in conventional in vitro fertilisation (IVF) cycles.DesignA retrospective cohort study.SettingData from August 2017 to August 2021 were collected from the electronic records of a large obstetrics and gynaecology hospital in Sichuan, China.ParticipantsA total of 11 598 eligible patients who underwent the first IVF cycles were included. All patients were randomly divided into the training group (n=8129) and the validation group (n=3469) in a 7:3 ratio.Primary outcome measureThe incidence of LFR and TFF.ResultsLogistic regressions showed that ovarian stimulation protocol, primary infertility and initial progressive sperm motility were the independent predictors of LFR, while serum luteinising hormone and P levels before human chorionic gonadotropin injection and number of oocytes retrieved were the critical predictors of TFF. And these indicators were incorporated into the nomogram models. According to the area under the curve values, the predictive ability for LFR and TFF were 0.640 and 0.899 in the training set and 0.661 and 0.876 in the validation set, respectively. The calibration curves also showed good concordance between the actual and predicted probabilities both in the training and validation group.ConclusionThe novel nomogram models provided effective methods for clinicians to predict LFR and TFF in traditional IVF cycles.

Chromatin-modifying enzymes, especially protein arginine methyltransferases (PRMTs), have been identified as candidate targets for cancer. Cellular or animal-based evidence has suggested an association between coactivator-linked arginine methyltransferase 1 (CARM1) and cancer progression. However, the relationship between CARM1 and patient prognosis and immune infiltration in pancancer patients is unknown. On the basis of the GEO and TCGA databases, we first investigated the possible oncogenic functions of CARM1 in thirty-three tumor types. CARM1 expression was elevated in many types of tumors. In addition, there was a significant association between CARM1 expression and the survival rate of tumor patients. Uterine corpus endometrial carcinoma (UCES) samples had the highest CARM1 mutation frequency of all cancer types. In head and neck squamous cell carcinoma (HNSC) and lung squamous cell carcinoma (LUSC), CARM1 expression was associated with the level of CD8+ T cell infiltration, and cancer-associated fibroblast infiltration was also observed in other tumors including kidney renal papillary cell carcinoma (KIRC) and prostate adenocarcinoma (PRAD). CARM1 was involved in immune modulation and played an important role in the tumor microenvironment (TME). Furthermore, activities associated with RNA transport and its metabolism were included in the possible mechanisms of CARM1. Herein, our first pancancer research explores the oncogenic role of CARM1 in various tumors. CARM1 is associated with immune infiltrates and can be employed as a predictive biomarker in pancancer.

PurposeThe spread of the Internet has transformed the dating landscape. Given the increasing popularity of online dating and rising immigration to Canada, this study takes an intersectional lens to examine nativity and gender differentials in heterosexual online dating.Design/methodology/approachIn 2018, a random-digit-dial telephone survey was conducted in Canada. Logistic regression models were used to analyze original data from this survey (N = 1,373).FindingsResults show that immigrants are more likely than native-born people to have used online dating in Canada, possibly because international relocation makes it more difficult for immigrants to meet romantic partners in other ways. In online-to-offline transitions, both native-born and immigrant online daters follow gendered scripts where men ask women out for a first date. Finally, immigrant men, who likely have disadvantaged positions in offline dating markets, also experience the least success in finding a long-term partner online.Originality/valueExtending search theory of relationship formation to online dating, this study advances the understanding of change and continuity in gendered rituals and mate-selection processes in the digital and globalization era. Integrating search theory and intersectionality theory, this study highlights the efficiency of using the Internet to search for romantic partners and the socially constructed hierarchy of desirability as interrelated mechanisms that produce divergent online dating outcomes across social groups. Internet dating, instead of acting as an agent of social change, may reproduce normative dating practices and existing hierarchies of desirability.

Three-dimensional (3-D) freehand ultrasound (US) imaging has been applied to the investigation of spine deformity. However, it is a challenge for the current 3-D imaging reconstruction algorithms to achieve a balance between image quality and computation time. The objectives of this article are to implement a new fast reconstruction algorithm that can fulfill the request of immediate demonstration and processing for high-quality 3-D spine imaging, and to evaluate the reliability and accuracy of scoliotic curvature measurement when using the algorithm. The fast dot-projection (FDP) algorithm was applied for voxel-based nearest neighbor (VNN), multiple plane interpolation (MPI), and pixel nearest neighbor (PNN) protocols to reduce the reconstruction time. The 3-D image volume was reconstructed from the datasets acquired from scoliotic subjects. The computational cost, image characteristics, and statistical analyses of curve measurements were compared and evaluated among different reconstruction protocols. The results illustrated that the 3-D spine images using the FDP-MPI4 algorithm showed higher brightness (20%), contrast (14%), and signal-to-noise ratio (SNR) (26%) than FDP-VNN. The measurement performed by trainee rater exhibited significant improvement in measurement reliability and accuracy using FDP-MPI4 in comparison with FDP-VNN ( ${p} ), and the intraclass correlation coefficient (ICC) of interrater measurement increased from 0.88 to 0.96. The FDP-PNN method could acquire and reconstruct spine images simultaneously and present the results in 1–2 min, which showed the potential to provide the approximate real-time visualization for fast screening.

Ochratoxin A (OTA) is one of the most common toxins in food and feed, which seriously affects the health of public. Herein, a convenient biosensor for OTA detecting was built based on graphene oxide (GO) and quantum dots-aptamer (QDs-aptamer) in this investigation. The results in our study demonstrated that the constructed biosensor shows excellent sensitivity and highly selectivity for OTA. A lower limit of detection of 376.3 pM (equivalent to 0.152 ng·mL−1) was achieved in the linear range from 0.5 to 20 nM (R2 = 0.996) under optimized conditions. In addition, the constructed sensor was challenged by testing coffee and red wine samples that contained buffer solution spiked with different concentrations of OTA. Considering easy operating and superior sensitivity, it has great potential, provides a high-performance platform for OTA testing in complicated food sample, and also affords a pathway for analysis of other aptamer-specific molecules.

A triggered communication mechanism-based adaptive control strategy is proposed for output consensus of a class of uncertain nonlinear multi-agent systems. A distributed estimator is constructed vi...

BACKGROUND Heterotopic cesarean scar pregnancy (HCSP) is very rare and has a high risk of massive uterine bleeding. Preservation of concurrent intrauterine pregnancy (IUP) is one of the great challenges in the management of HCSP. No universal treatment protocol has been established when IUP is desired to be preserved. CASE SUMMARY We report a case of HCSP at 8+ wk gestation in a 34-year-old woman with stable hemodynamics. A two-step intervention was applied. Selective embryo aspiration was performed first, and surgical removal of ectopic gestational tissue by suction and curettage was performed 2 d later. Both steps were performed under ultrasound guidance. The patient had an uneventful course, and a healthy baby was delivered at 34+6 wk gestation. CONCLUSION Selective embryo aspiration followed by suction and curettage was successful in the preservation of IUP in the management of HCSP. This approach is an alternative option for HCSP in the first trimester when the IUP is desired to be preserved.

Since microRNA-205 (miRNA-205) is a predictive biomarker for antiradiation of nasopharyngeal carcinoma (NPC), quantitative detection of miRNA-205 is important for developing personalized strategies for the treatment of NPC. In this investigation, based on the graphene oxide (GO) sensor and hybridization chain reaction (HCR) for fluorescence signal amplification, a highly sensitive and selective detection method for miRNA-205 was designed. A target-recycling mechanism is employed, where a single miRNA-205 target triggers the signal amplification of many DNA signal probes. The biosensor shows the ability to analyze miRNA-205 in solution, and it can detect miRNA-205 at concentrations as low as 311.96 pM. Furthermore, the method is specific in that it distinguishes between a target miRNA and a sequence with single-, double-, and three-base mismatches, as well as other miRNAs. Considering its simplicity and superior sensitivity, it was also verified in 1‰ serum with a detection limit of 111.65 pM. Importantly, the method successfully demonstrated that miRNA-205 could be imaged in living cells, which provided the possibility of localizing target molecules in live cell imaging applications. This method has great clinical application potential in the determination of miRNA-205, a biomarker for radiation-resistant NPC.

Shujuan Chu,1 Zhilin Wu,1 Zhouyang Wu,1 Jing Wu,1 Yue Qian2 1Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 2Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of ChinaCorrespondence: Jing Wu; Yue Qian Email tounj_002@163.com; qianyue011@sohu.comBackground: The causal relationship between insomnia and migraine is contradictory and no study has been carried out among the Chinese population to date.Methods: In this case, we conducted a case–control study and a bidirectional mendelian randomization (MR) analysis to determine whether insomnia is causally related to the development of migraine. The instrumental variables for insomnia were derived from the largest genome-wide association study of 1,331,010 participants, while the genetic instruments for migraine were available from the largest meta-analysis of migraine with 59,674 cases and 316,078 controls.Results: In case–control study, subjects with insomnia have significantly higher risk of migraine (OR=4.29, 95% CI: 3.21– 5.74, P< 0.001), compared with those without insomnia. The bidirectional two-sample MR analysis revealed that insomnia was significantly associated with higher risk of migraine (OR=1.24, 95% CI: 1.11– 1.38, P=1.01× 10-4), and the results were validated in the UK Biobank data. The results showed no indication for directional pleiotropy effects as assessed by the MR-Egger intercept (P> 0.05).Conclusion: Conclusively, our study highlighted that increased migraine risk was confined to subjects with a genetic pre-disposition to insomnia, and these findings had potential implications for improving the sleep quality to reduce the burden of migraine.Keywords: mendelian randomization, insomnia, migraine, case–control

Background Bone cancer patients are often accompanied with pain and depression, which seriously affects their quality of life and survival time. Fluoxetine, a selective serotonin reuptake inhibitor, has been reported to be effective not only in reducing depression-like behaviors but also in alleviating cancer pain. However, the specific mechanisms involved remain obscure. Methods Bone cancer mice were treated with fluoxetine for 7 consecutive days after the formation of pain and depression symptoms. Neuroinflammation and synaptic changes at the basolateral amygdala (BLA) after treatment were examined with western blotting, immunofluorescence and Golgi-Cox staining. Results Compared with the tumor group, fluoxetine significantly improved the mechanical allodynia and sugar water preference ratio, and reduced the immobility time of forced swimming. In addition, we found fluoxetine had an inhibitory effect on reactive glial cells and neurotoxic glial cells of bone cancer pain (BCP) mice. Meanwhile, fluoxetine could improve synaptic function in the bone cancer mice basolateral amygdala regions. Conclusions Fluoxetine can effectively alleviate pain-like and depression-related behaviors in BCP model. The concerned mechanisms may be related to reducing neurotoxic glial cells activation and promoting synapse formation at BLA.