Trends in cardiovascular disease incidence among 22 million people in the UK over 20 years: population based study.

OBJECTIVE: To investigate the incidence of cardiovascular disease (CVD) overall and by age, sex, and socioeconomic status, and its variation over time, in the UK during 2000-19. DESIGN: Population based study. SETTING: UK. PARTICIPANTS: 1 650 052 individuals registered with a general practice contributing to Clinical Practice Research Datalink and newly diagnosed with at least one CVD from 1 January 2000 to 30 June 2019. MAIN OUTCOME MEASURES: The primary outcome was incident diagnosis of CVD, comprising acute coronary syndrome, aortic aneurysm, aortic stenosis, atrial fibrillation or flutter, chronic ischaemic heart disease, heart failure, peripheral artery disease, second or third degree heart block, stroke (ischaemic, haemorrhagic, and unspecified), and venous thromboembolism (deep vein thrombosis or pulmonary embolism). Disease incidence rates were calculated individually and as a composite outcome of all 10 CVDs combined and were standardised for age and sex using the 2013 European standard population. Negative binomial regression models investigated temporal trends and variation by age, sex, and socioeconomic status. RESULTS: The mean age of the population was 70.5 years and 47.6% (n=784 904) were women. The age and sex standardised incidence of all 10 prespecified CVDs declined by 19% during 2000-19 (incidence rate ratio 2017-19 v 2000-02: 0.80, 95% confidence interval 0.73 to 0.88). The incidence of coronary heart disease and stroke decreased by about 30% (incidence rate ratios for acute coronary syndrome, chronic ischaemic heart disease, and stroke were 0.70 (0.69 to 0.70), 0.67 (0.66 to 0.67), and 0.75 (0.67 to 0.83), respectively). In parallel, an increasing number of diagnoses of cardiac arrhythmias, valve disease, and thromboembolic diseases were observed. As a result, the overall incidence of CVDs across the 10 conditions remained relatively stable from the mid-2000s. Age stratified analyses further showed that the observed decline in coronary heart disease incidence was largely restricted to age groups older than 60 years, with little or no improvement in younger age groups. Trends were generally similar between men and women. A socioeconomic gradient was observed for almost every CVD investigated. The gradient did not decrease over time and was most noticeable for peripheral artery disease (incidence rate ratio most deprived v least deprived: 1.98 (1.87 to 2.09)), acute coronary syndrome (1.55 (1.54 to 1.57)), and heart failure (1.50 (1.41 to 1.59)). CONCLUSIONS: Despite substantial improvements in the prevention of atherosclerotic diseases in the UK, the overall burden of CVDs remained high during 2000-19. For CVDs to decrease further, future prevention strategies might need to consider a broader spectrum of conditions, including arrhythmias, valve diseases, and thromboembolism, and examine the specific needs of younger age groups and socioeconomically deprived populations.

An induced mutation of ABC-transporter component VraF(K84E) contributes to vancomycin resistance and virulence in Staphylococcus aureus strain MW2.

Staphylococcus aureus is a notorious pathogen responsible for various severe diseases. Due to the emergence of drug-resistant strains, the prevention and treatment of S. aureus infections have become increasingly challenging. Vancomycin is considered to be one of the last-resort drugs for treating most methicillin-resistant S. aureus (MRSA), so it is of great significance to further reveal the mechanism of vancomycin resistance. VraFG is one of the few important ABC (ATP-binding cassette) transporters in S. aureus that can form TCS (two-component systems)/ABC transporter modules. ABC transporters can couple the energy released from ATP hydrolysis to translocate solutes across the cell membrane. In this study, we obtained a strain with decreased vancomycin susceptibility after serial passaging and selection. Subsequently, whole-genome sequencing was performed on this laboratory-derived strain MWA2 and a novel single point mutation was discovered in vraF gene, leading to decreased sensitivity to vancomycin and daptomycin. Furthermore, the mutation reduces autolysis of S. aureus and downregulates the expression of lytM, isaA, and atlA. Additionally, we observed that the mutant has a less net negative surface charge than wild-type strain. We also noted an increase in the expression of the dlt operon and mprF gene, which are associated with cell surface charge and serve to hinder the binding of cationic peptides by promoting electrostatic repulsion. Moreover, this mutation has been shown to enhance hemolytic activity, expand subcutaneous abscesses, reflecting an increased virulence. This study confirms the impact of a point mutation of VraF on S. aureus antibiotic resistance and virulence, contributing to a broader understanding of ABC transporter function and providing new targets for treating S. aureus infections.

Simple Isopropanol-Assisted Direct Soft Imprint Lithography for Residue-Free Microstructure Patterning.

A direct soft imprint lithography was proposed to realize the direct fabrication of residue-free, well-shaped functional patterns through a single step. This imprint method requires only a simply prepared isopropanol-treated polydimethylsiloxane (PDMS) stamp without any additional resists. Residue-free Ag patterns were successfully fabricated on different substrates by directly imprinting the Ag ink with the isopropanol-treated PDMS stamp. Furthermore, the coffee-ring effect of the imprinting Ag patterns can be eliminated by optimizing the imprinting time, isopropanol-treating time, and imprinting temperatures. Studies show that the residual Ag ink in the contact region can be absorbed by the isopropanol-treated PDMS stamp due to the "like dissolves like" principle. Finally, this method was employed to fabricate the Ag electrodes for the thin-film transistors, attaining a mobility of ∼8 cm2 V-1 s-1, which is comparable to those with vacuum-processed electrodes. This process provides a simple, low-cost, residue-free, coffee-ring-free, and fast patterning method in the field of microelectronics.

Single-cell RNA sequencing reveals S100a9hi macrophages promote the transition from acute inflammation to fibrotic remodeling after myocardial ischemia‒reperfusion.

Rationale: The transition from acute inflammation to fibrosis following myocardial ischemia‒reperfusion (MIR) significantly affects prognosis. Macrophages play a pivotal role in inflammatory damage and repair after MIR. However, the heterogeneity and transformation mechanisms of macrophages during this transition are not well understood. Methods: In this study, we used single-cell RNA sequencing (scRNA-seq) and mass cytometry to examine murine monocyte-derived macrophages after MIR to investigate macrophage subtypes and their roles in the MIR process. S100a9-/- mice were used to establish MIR model to clarify the mechanism of alleviating inflammation and fibrosis after MIR. Reinfusion of bone marrow-derived macrophages (BMDMs) after macrophage depletion (MD) in mice subjected to MIR were performed to further examine the role of S100a9hi macrophages in MIR. Results: We identified a unique subtype of S100a9hi macrophages that originate from monocytes and are involved in acute inflammation and fibrosis. These S100a9hi macrophages infiltrate the heart as early as 2 h post-reperfusion and activate the Myd88/NFκB/NLRP3 signaling pathway, amplifying inflammatory responses. As the tissue environment shifts from proinflammatory to reparative, S100a9 activates transforming growth factor-ß (Tgf-ß)/p-smad3 signaling. This activation not only induces the transformation of myocardial fibroblasts to myofibroblasts but also promotes fibrosis via the macrophage-to-myofibroblast transition (MMT). Targeting S100a9 with a specific inhibitor could effectively mitigate acute inflammatory damage and halt the progression of fibrosis, including MMT. Conclusion: S100a9hi macrophages are a promising therapeutic target for managing the transition from inflammation to fibrosis after MIR.

The association between human milk fatty acid composition in mothers with an elevated body mass index and infant growth changes.

BACKGROUND & AIMS: Few studies have investigated alternations in human milk polyunsaturated fatty acid (PUFA) composition in the context of maternal obesity and its effects on infant growth trajectories. This study explored whether maternal weight status and breastfeeding type influence human milk FA composition and infant anthropometry during the first six months of life. METHODS: Mother-infant dyads were enrolled from the Prediction of Allergies in Taiwanese Children birth cohort study. Data concerning maternal pre-pregnancy weight, infants' breastfeeding practices, and anthropometric data were obtained regularly. We identified and compared between the composition of 30 FAs in the colostrum and 2-month milk, respectively, in obese/overweight (OB/OW) and normal-weight (NW) mothers. Multiple linear regression analyses were performed to determine the association between PUFA composition at different lactation stages and infant anthropometric parameter changes and to identify the independent variables for body mass index (BMI) z-scores by six months of age. RESULTS: We included 338 mother-infant dyads (OB/OW mothers, 16.9 %). OB/OW mothers exhibited lower total n-3 PUFAs (P = 0.035), higher ratios of arachidonic acid (C20:4n-6)/eicosapentaenoic acid (C20:5n-3) + docosahexaenoic acid (C22:6n-3), and n-6/n-3 PUFA in colostrum (P = 0.037 and 0.011, respectively), and their offspring had higher body weight and BMI z-scores. Nevertheless, no PUFA composition or n-6/n-3 PUFA ratios in colostrum and 2-month milk were associated with anthropometric parameter changes by age 6 months. Infant birth weight z-scores were independently associated with BMI outcomes at age 6 months (adjusted ß = 0.16, 95 % confidence interval (0.05-0.35), P = 0.010) CONCLUSION: Neither n-3 nor n-6 PUFA profiles nor n-6/n-3 PUFA ratios at different lactation stages were found to be associated with anthropometric changes by age 6 months, suggesting that human milk PUFA composition may not be an important determinant of early infant growth trajectories.

Parity and incident type 2 diabetes in older Chinese women: Guangzhou Biobank Cohort Study.

This study examined the association between parity and incident type 2 diabetes in older Chinese women and estimated the mediation effect of adiposity indicators. A total of 11,473 women without diabetes at baseline from 2003 to 2008 were followed up until 2012. We used Cox proportional hazards regression to assess the association between parity and incident type 2 diabetes, and mediation analysis to estimate the mediation effect of adiposity indicators. Compared to women with one parity, the hazard ratio (HR) (95% confidence interval (CI)) for incident type 2 diabetes was 0.85 (0.44-1.63), 1.20 (1.11-1.30), 1.28 (1.16-1.41) and 1.27 (1.14-1.42) for women with parity of 0, 2, 3, and ≥ 4, respectively. The proportion of indirect effect (95% CI) mediated by body mass index, waist circumference, hip circumference, waist-to-hip ratio, waist-to-height ratio and body fat percentage was 26.5% (19.2-52.2%), 54.5% (39.4-108.7%), 25.1% (18.2-49.1%), 35.9% (25.6-74.1%), 50.3% (36.5-98.6%) and 15.1% (- 66.4 to 112.3%), respectively. Compared to women with one parity, women with multiparity (≥ 2) had a higher risk of incident type 2 diabetes and up to half of the association was mediated by abdominal obesity.

Precise determination of major and trace elements in micrometer-scale ilmenite lamellae in titanomagnetite using LA-ICP-MS technique: application of regression analysis to time-resolved signals.

Laser ablation ICP-MS (LA-ICP-MS) is a powerful microbeam technique capable of rapid and precise determination for a large spectrum of trace elements at ppm or sub-ppm levels. Micrometer-scale minerals and inclusions are very common in geological materials, for which direct measurement is restricted by the spot size using LA-ICP-MS (generally 20-50 µm). In this study, ilmenite lamellae intergrown with magnetite were selected as an example to describe a practical algorithm that applies regression analysis to extract the chemical compositions of binary phases from mixed LA-ICP-MS signals. The method accuracy is confirmed by the agreement between the regressed value for various trace elements in ilmenite exsolutions and their reference values (direct analyses using EPMA and LA-ICP-MS). Results were obtained for most detectable components (Mg, Mn, V, Nb, Ta, Sc, Zr, Hf, Sn, et c.) and their relative deviations are within ±10%, even for those <10 ppm (such as Hf and W). Relative standard errors on the regressed value were calculated to evaluate the precision of the method, which is mostly within 10%, and the worst up to 25%. Therefore, the algorithm described in this contribution provides a solution for precise determination of trace element compositions for micrometer-scale ilmenite lamellae in titanomagnetite using LA-ICP-MS, and is potentially practical for other geological materials.

Pharmacological Inhibition of P-Rex1/Rac1 Axis Blocked Angiotensin II-Induced Cardiac Fibrosis.

PURPOSE: Phosphatidylinositol-3,4,5-trisphosphate-dependent Rac exchange factor-1 (P-Rex1), as one of the members of Rac-GEFs, has been proven to play a critical role in cancer progression and metastasis. Nonetheless, its role in cardiac fibrosis remains elusive. In the present study, we aimed to investigate whether and how the P-Rex1 mediates AngII-induced cardiac fibrosis. METHOD: A cardiac fibrosis mouse model was established by chronic AngII perfusion. The heart structure, function, pathological changes of myocardial tissues, oxidative stress, and cardiac fibrotic protein expression were determined in an AngII induced mouse model. To provide a molecular mechanism for P-Rex1 involvement in cardiac fibrosis, a specific inhibitor or siRNA was used to block P-Rex1, and target the relationship between Rac1-GTPase and its downstream effector. RESULTS: Blocking P-Rex1 showed down-regulation of its downstream effectors such as the profibrotic transcriptional regulator Paks, ERK1/2, and ROS generation. Intervention treatment with P-Rex1 inhibitor 1A-116 ameliorated AngII-induced abnormalities in heart structure and function. Moreover, pharmacological inhibition of the P-Rex1/Rac1 axis showed a protective effect in AngII-induced cardiac fibrosis through the down-regulation of collagen1, CTGF, and α-SMA expression. CONCLUSION: Our findings demonstrated for the first time that P-Rex1 was an essential signaling mediator in CFs activation and subsequent cardiac fibrosis, and 1A-116 could be a potential pharmacological development drug.

Strain Tunability of Perpendicular Magnetic Anisotropy in van der Waals Ferromagnets VI3.

Layered ferromagnets with strong magnetic anisotropy energy (MAE) have special applications in nanoscale memory elements in electronic circuits. Here, we report a strain tunability of perpendicular magnetic anisotropy in van der Waals (vdW) ferromagnets VI3 using magnetic circular dichroism measurements. For an unstrained flake, the M-H curve shows a rectangular-shaped hysteresis loop with a large coercivity (1.775 T at 10 K) and remanent magnetization. Furthermore, the coercivity can be enhanced to a maximum of 2.6 T under a 3.8% external in-plane tensile strain. Our DFT calculations show that the increased MAE under strain contributes to the enhancement of coercivity. Meanwhile, the strain tunability on the coercivity of CrI3, with a similar crystal structure, is limited. The main reason is the strong spin-orbit coupling in V3+ in VI6 octahedra in comparison with that in Cr3+. The strain tunability of coercivity in VI3 flakes highlights its potential for integration into vdW heterostructures.

The Mechanism of the Photostability Enhancement of Thin-Film Transistors Based on Solution-Processed Oxide Semiconductors Doped with Tetravalent Lanthanides.

The applications of thin-film transistors (TFTs) based on oxide semiconductors are limited due to instability under negative bias illumination stress (NBIS). Here, we report TFTs based on solution-processed In2O3 semiconductors doped with Pr4+ or Tb4+, which can effectively improve the NBIS stability. The differences between the Pr4+-doped In2O3 (Pr:In2O3) and Tb4+-doped In2O3 (Tb:In2O3) are investigated in detail. The undoped In2O3 TFTs with different annealing temperatures exhibit poor NBIS stability with serious turn-on voltage shift (ΔVon). After doping with Pr4+/Tb4+, the TFTs show greatly improved NBIS stability. As the annealing temperature increases, the Pr:In2O3 TFTs have poorer NBIS stability (ΔVon are -3.2, -4.8, and -4.8 V for annealing temperature of 300, 350, and 400 °C, respectively), while the Tb:In2O3 TFTs have better NBIS stability (ΔVon are -3.6, -3.6, and -1.2 V for annealing temperature of 300, 350, and 400 ℃, respectively). Further studies reveal that the improvement of the NBIS stability of the Pr4+/Tb4+:In2O3 TFTs is attributed to the absorption of the illuminated light by the Pr/Tb4fn-O2p6 to Pr/Tb 4fn+1-O2p5 charge transfer (CT) transition and downconversion of the light to nonradiative transition with a relatively short relaxation time compared to the ionization process of the oxygen vacancies. The higher NBIS stability of Tb:In2O3 TFTs compared to Pr:In2O3 TFTs is ascribed to the smaller ion radius of Tb4+ and the lower energy level of Tb 4f7 with a isotropic half-full configuration compared to that of Pr 4f1, which would make it easier for the Tb4+ to absorb the visible light than the Pr4+.

Niacin skin flush and membrane polyunsaturated fatty acids in schizophrenia from the acute state to partial remission: a dynamic relationship.

Despite the consistent finding of an attenuated niacin-induced flush response in schizophrenia, its long-term stability and relationship to the membrane polyunsaturated fatty acid (PUFA) levels remain unknown. We conducted niacin skin tests and measured the membrane PUFAs using gas chromatography among 46 schizophrenia inpatients and 37 healthy controls at the baseline and the 2-month follow-up. Attenuated flush responses were persistently observed in schizophrenia patients in both acute and partial remission states, whereas an increased flush response was found in the controls. A persistent decrease in both dihomo-gamma-linolenic acid and docosahexaenoic acid and an increased turnover of arachidonic acid (ARA) via endogenous biosynthesis were found in schizophrenia patients. A composite niacin flush score by combining those with a control-to-case ratio of >1.4 (i.e., scores at 5 min of 0.1 M, 0.01 M, and 0.001 M + 10 min of 0.01 M and 0.001 M + 15 min of 0.001 M) at the baseline was correlated positively with ARA levels among controls but not among schizophrenia patients, whereas the flush score at the 2-month follow-up was correlated positively with ARA levels among patients. The 2-month persistence of attenuated niacin-induced flush response in schizophrenia patients implies that the niacin skin test might tap a long-term vulnerability to schizophrenia beyond acute exacerbation.

Hard ferromagnetic behavior in atomically thin CrSiTe3 flakes.

The research on two-dimensional (2D) van der Waals (vdW) magnets has promoted the development of ultrahigh-density data storage and nanoscale spintronic devices. However, the soft ferromagnetic behavior in most 2D magnets, which means the absence of remanent magnetization, severely limits their applications in realistic devices. Here, we report a layer-controlled ferromagnetic behavior in atomically thin CrSiTe3 flakes, where a transition from the soft to the hard ferromagnetic state occurs as the thickness of samples decreases down to several nanometers. Phenomenally, in contrast to the negligible hysteresis loop in the bulk counterparts, atomically thin CrSiTe3 shows a rectangular loop with finite magnetization and coercivity as the thickness decreases down to ∼8 nm, indicative of a single-domain and out-of-plane ferromagnetic order. We find that the stray field is weakened with decreasing thickness, which suppresses the formation of the domain wall. In addition, thickness-dependent ferromagnetic properties also reveal a crossover from 3 dimensional to 2 dimensional Ising ferromagnets, accompanied by a drop of the Curie temperature from 33 K for bulk to ∼17 K for the 4 nm sample. Our study paves the way towards exploring and learning much more about atomically thin and layered intrinsic ferromagnets.

Dimethyl Fumarate Combined With Vemurafenib Enhances Anti-Melanoma Efficacy via Inhibiting the Hippo/YAP, NRF2-ARE, and AKT/mTOR/ERK Pathways in A375 Melanoma Cells.

Melanoma is a deadly form of skin cancer with high rates of resistance to traditional chemotherapy and radiotherapy. BRAF inhibitors (BRAFi) can achieve initial efficacy when used to treat melanoma patients, but drug resistance and relapse are common, emphasizing the need for new therapeutic strategies. Herein, we reported that combination of dimethyl fumarate (DMF) and vemurafenib (Vem) inhibited melanoma cell proliferation more significantly and induced more cell death than single agent did both in vitro and in vivo. DMF/Vem treatment induced cell death through inhibiting the expression and transcriptional activity of NRF2 thereby resulting in more reactive oxygen species (ROS) and via inhibiting the expression of YAP, a key downstream effector of Hippo pathway. DMF/Vem treatment also reduced phosphorylation of AKT, 4EBP1, P70S6K and ERK in AKT/mTOR/ERK signaling pathways. RNA-seq analysis revealed that DMF/Vem treatment specifically suppressed 4561 genes which belong to dozens of cell signaling pathways. These results indicated that DMF/Vem treatment manifested an enhanced antitumor efficacy through inhibiting multiple cell signaling pathways, and thus would be a novel promising therapeutic approach targeted for melanoma.

Optimization of Decoloration Conditions of Methylene Blue Wastewater by Penicillium P1.

The objective of this work was to optimize the decolorization of methylene blue dye wastewater by Penicillium P1. The influencing factors included initial methylene blue concentration, initial pH value, salinity and inoculation percentage of penicillium spores. The decolorization rate was optimized by response surface center composite design methods. The optimal optimization condition was methylene blue concentration 50 mg/L, pH value 3.61, salinity 3.7%, and inoculation percentage 3.21% (When the MSM was 100 ml), the predicted decolorization rate of methylene blue 85%. The UV and the FTIR spectrum analysis showed that the structure of methylene blue changed during the process of decolorization of methylene blue by Penicillium P1.

Structure-property relationships of photofunctional diiridium(II) complexes with tetracationic charge and an unsupported Ir-Ir bond.

In contrast to the extensively studied dirhodium(II) complexes and iridium(III) complexes, neutral or dicationic dinuclear iridium(II) complexes with an unsupported ligand are underdeveloped. Here, a series of tetracationic dinuclear iridium(II) complexes, featuring the unsupported Ir(II)-Ir(II) single bond with long bond distances (2.8942(4)-2.9731(4) Å), are synthesized and structurally characterized. Interestingly, compared to the previous unsupported neutral or dicationic diiridium(II) complexes, our DFT and high-level DLPNO-CCSD(T) results found the largest binding energy in these tetracationic complexes even with the long Ir(II)-Ir(II) bond. Our study further reveals that London dispersion interactions enhance the stability cooperatively and significantly to overcome the strong electrostatic repulsion between two half dicationic metal fragments. This class of complexes also exhibit photoluminescence in solution and solid states, which, to our knowledge, represents the first example of this unsupported dinuclear iridium(II) system. In addition, their photoreactivity involving the generation of iridium(II) radical monomer from homolytic cleavage was also explored. The experimental results of photophysical and photochemical behaviours were also correlated with computational studies.

Hypoxic in vitro culture reduces histone lactylation and impairs pre-implantation embryonic development in mice.

BACKGROUND: Dynamic changes of histone posttranslational modifications are important contexts of epigenetic reprograming after fertilization in pre-implantation embryos. Recently, lactylation has been reported as a novel epigenetic modification that regulates various cellular processes, but its role during early embryogenesis has not been elucidated. RESULTS: We examined nuclear accumulation of H3K23la, H3K18la and pan histone lactylation in mouse oocytes and pre-implantation embryos by immunofluorescence with specific antibodies. All of the three modifications were abundant in GV stage oocytes, and both H3K23la and pan histone lactylation could be detected on the condensed chromosomes of the MII oocytes, while H3K18la were not detected. After fertilization, the nuclear staining of H3K23la, H3K18la and pan histone lactylation was faint in zygotes but homogeneously stained both of the parental pronuclei. The signal remained weak in the early cleavage stage embryos and increased remarkably in the blastocyst stage embryos. Comparison of the embryos cultured in four different conditions with varying concentrations of oxygen found that H3K23la, H3K18la and pan histone lactylation showed similar and comparable staining pattern in embryos cultured in atmospheric oxygen concentration (20% O2), gradient oxygen concentration (5% O2 to 2% O2) and embryos obtained from in vivo, but the modifications were greatly reduced in embryos cultured in hypoxic condition (2% O2). In contrast, nuclear accumulation of H3K18ac or H3K23ac was not significantly affected under hypoxic condition. Moreover, the developmental rate of in vitro cultured embryo was significantly reduced by low oxygen concentration and small molecule inhibition of LDHA activity led to decreased lactate production, as well as reduced histone lactylation and compromised developmental rate. CONCLUSIONS: We provided for the first time the dynamic landscape of H3K23la, H3K18la and pan histone lactylation in oocytes and pre-implantation embryos in mice. Our data suggested that histone lactylation is subjected to oxygen concentration in the culture environment and hypoxic in vitro culture reduces histone lactylation, which in turn compromises developmental potential of pre-implantation embryos in mice.

Pressure-Enhanced Ferromagnetism in Layered CrSiTe3 Flakes.

Despite recent advances in layered ferromagnets, ferromagnetic interactions in these materials are rather weak. Here, we report pressure-enhanced ferromagnetism in layered CrSiTe3 flakes revealed by high-pressure magnetic circular dichroism measurements. Below ∼3 GPa, CrSiTe3 undergoes a paramagnetic-to-ferromagnetic phase transition at ∼32 K, and the field-induced spin-flip in the ferromagnetic phase produces nearly zero hysteresis loops, demonstrating soft ferromagnetism. Above ∼4 GPa, a soft-to-hard ferromagnetic transition occurs, signaled by rectangular-shaped hysteresis loops with finite coercivity and remanent magnetization. Interestingly, as pressure increases, the Curie temperature and coercivity dramatically increase up to ∼138 K and 0.17 T at 7.8 GPa, respectively, in contrast to ∼36 K and 0.02 T at 4.6 GPa. It indicates a remarkable influence of pressure on exchange interactions, which is consistent with DFT calculations. The effective interaction between magnetic couplings and external pressure offers new opportunities in pursuit of high-temperature layered ferromagnets.

Natural menopausal age and cardiovascular disease risk factors in older Chinese women: Guangzhou Biobank Cohort Study.

OBJECTIVE: To examine the associations of natural menopausal age with cardiovascular disease risk factors and whether the associations varied by parity in older Chinese women. METHODS: Information of demographic characteristics, lifestyles, and reproductive factors was collected by face-to-face interview. Framingham Risk Score was used as an indicator of cardiovascular disease risk, with a score ≥ 10% considered as high cardiovascular disease risk (vs low, dichotomous). Multivariable logistic and linear regressions were used to examine the associations of menopausal age with cardiovascular disease risk factors. RESULTS: Of 18,339 women aged 50+ years, the average (standard deviation) age was 61.8 (6.9) years. Compared with women with menopausal age of 45 to 54 years, after adjustment for multiple potential confounders, women with menopausal age <45 years or ≥55 years had higher Framingham Risk Score (0.93%, 95% confidence interval: 0.40-1.46, and 0.69%, 95% confidence interval: 0.18-1.20, respectively). Women with menopausal age <45 or ≥55 years had higher odds of high cardiovascular disease risk (vs low) (odds ratio [95% confidence interval]:1.26 (1.10-1.44) and 1.17 (1.02-1.33), respectively). The associations of menopausal age with the Framingham Risk Score varied by parity (P for interaction ≤0.001). The Framingham Risk Score was higher in those with one to three parity (<45 y: 1.01 [0.43-1.59]; ≥55 y: 1.14 [0.60-1.68]) and lower for parity ≥4 (<45 y: -0.33 [-1.84 to 1.18]; ≥55 y: -2.02 [-3.82 to -0.22]). In nulliparous women, the Framingham Risk Score was highest in menopausal age <45 years (3.97 [1.67-6.26]), but the differences were nonsignificant in menopausal age ≥55 years (0.66 [-1.38 to 2.71]). CONCLUSIONS: Both early and late natural menopausal ages were associated with a higher cardiovascular disease risk, and the associations were stronger in those with lower parity.

Video Summary:http://links.lww.com/MENO/A813 .

Phosphoproteomics Analysis Reveals a Pivotal Mechanism Related to Amino Acid Signals in Goat Fetal Fibroblast.

In addition to serving as the building blocks for protein synthesis, amino acids serve as critical signaling molecules in cells. However, the mechanism through which amino acid signals are sensed in cells is not yet fully understood. This study examined differences in the phosphorylation levels of proteins in response to amino acid signals in Cashmere goat fetal fibroblasts (GFb). Amino acid deficiency was found to induce autophagy and attenuate mammalian/mechanistic target of rapamycin complex (mTORC1)/Unc-51-like autophagy activating kinase 1 (ULK1) signaling in GFb cells. A total of 144 phosphosites on 102 proteins positively associated with amino acid signaling were screened using phosphorylation-based proteomics analysis. The mitogen-activated protein kinase (MAPK) signaling pathway was found to play a potentially important role in the interaction network involved in the response to amino acid signals, according to gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and MAPK1/3 may serve as a central hub for the entire network. Motif analysis identified three master motifs, xxx_S_Pxx, xxx_S_xxE, and xxx_S_xDx, which were centered on those phosphosites at which phosphorylation was positively regulated by amino acid signaling. Additionally, the phosphorylation levels of three membrane proteins, the zinc transporter SLC39A7, the sodium-dependent neutral amino acid transporters SLC1A5 and SLC38A7, and three translation initiation factors, eukaryotic initiation factor (eIF)5B, eIF4G, and eIF3C, were positively regulated by amino acid signals. These pivotal proteins were added to currently known signaling pathways to generate a novel model of the network pathways associated with amino acid signals. Finally, the phosphorylation levels of threonine 203 and tyrosine 205 on MAPK3 in response to amino acid signals were examined by western blot analysis, and the results were consistent with the data from the phosphoproteomics analysis. The findings of this study provide new evidence and insights into the precise mechanism through which amino acid signals are sensed and conducted in Cashmere goat fetal fibroblasts.

New identification and significance of Early Cretaceous mafic rocks in the interior South China Block.

Early Cretaceous mafic rocks are first reported in the northern Guangxi region from the western Qin-Hang belt in the interior South China Block. A systematic investigation of zircon U-Pb dating, whole-rock geochemistry, Sm-Nd isotopes and zircon Hf-O isotopes for these mafic rocks reveals their petrogenesis and the mantle composition as well as a new window to reconstruct lithospheric evolution in interior South China Block during Late Mesozoic. Zircon U-Pb dating yielded ages of 131 ± 2 Ma to 136 ± 2 Ma for diabase and gabbro from Baotan area, indicating the first data for Early Cretaceous mafic magmatism in the western Qing-Hang belt. These mafic rocks show calc-alkaline compositions, arc-like trace element distribution patterns, low zircon εHf(t) of - 9.45 to - 6.17 and high δ18O values of + 5.72 to + 8.09‰, as well as low whole-rock εNd(t) values of - 14.27 to - 9.53. These data suggest that the studied mafic rocks are derived from an ancient lithospheric mantle source that was metasomatized during Neoproterozoic subduction. Thus, the occurrence of these mafic rocks indicates a reactivation of Neoproterozoic subducted materials during an extension setting at Late Mesozoic in the western Qin-Hang belt, an old suture zone that amalgamates the Yangtze and Cathaysia blocks.