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Pre-pregnancy obesity (ppOB) is linked to pregnancy complications and abnormal fetal growth through placental mechanisms, and long non-coding RNAs (lncRNAs) may play an epigenetic role in these processes. We investigated overall and sex-specific associations of pre-pregnancy body mass index (ppBMI), ppOB, and birthweight with placental lncRNA transcripts in two birth cohorts. Study participants were mother-child dyads recruited to the CANDLE (Memphis, TN)(n = 725) and GAPPS (Seattle and Yakima, WA)(n = 159) cohorts. Maternal ppBMI was assessed at enrollment using interviewer-administered questionnaires. LncRNAs (1,077 and 1,033 for CANDLE and GAPPS, respectively) were sequenced from placental samples collected at birth. Placental lncRNA was regressed on ppBMI, ppOB (ppBMI ≥30kg/m2), or continuous birthweight in cohort-specific weighted linear models controlling for a priori-specified confounders and experimental variables. Potential effect modification by infant-sex was examined in sex-stratified analyses and models including BMI-infant-sex interaction terms. No lncRNA transcripts were significantly associated with ppBMI, ppOB, or birthweight in primary models. Among male infants in CANDLE, expression of three lncRNA transcripts (ERVH48-1, AC139099.1, CEBPA-DT) was associated with ppBMI and one transcript (AC104083.1) with birthweight. In GAPPS, ppBMI was associated with two lncRNA transcripts (AP000879.1 and AL365203.2) among males, and birthweight was associated with 17 lncRNA transcripts (including LINC02709, KANSL1-AS1, DANCR, EPB41L4A-AS1, and GABPB1-AS1) among females. No BMI-infant-sex interactions were observed. Though many of these potential associations are for uncharacterized transcripts, several identified lncRNAs (e.g., ERVH48-1 and CEBPA-DT) have been linked to pathways controlling cancer or placental growth, trophoblast differentiation, and gene expression. These associations warrant validation in future studies.
Depression has been linked to disruptions in resting-state networks (RSNs). However, inconsistent findings on RSN disruptions, with variations in reported connectivity within and between RSNs, complicate the understanding of the neurobiological mechanisms underlying depression.
Methods
A systematic literature search of PubMed and Web of Science identified studies that employed resting-state functional magnetic resonance imaging (fMRI) to explore RSN changes in depression. Studies using seed-based functional connectivity analysis or independent component analysis were included, and coordinate-based meta-analyses were performed to evaluate alterations in RSN connectivity both within and between networks.
Results
A total of 58 studies were included, comprising 2321 patients with depression and 2197 healthy controls. The meta-analysis revealed significant alterations in RSN connectivity, both within and between networks, in patients with depression compared with healthy controls. Specifically, within-network changes included both increased and decreased connectivity in the default mode network (DMN) and increased connectivity in the frontoparietal network (FPN). Between-network findings showed increased DMN–FPN and limbic network (LN)–DMN connectivity, decreased DMN–somatomotor network and LN–FPN connectivity, and varied ventral attention network (VAN)–dorsal attentional network (DAN) connectivity. Additionally, a positive correlation was found between illness duration and increased connectivity between the VAN and DAN.
Conclusions
These findings not only provide a comprehensive characterization of RSN disruptions in depression but also enhance our understanding of the neurobiological mechanisms underlying depression.
This paper introduces a three-substrate layered transmitarray design that avoids the use of vias, aiming to produce broadband orbital angular momentum (OAM) vortex beams within the Ka-band. The suggested element configuration accomplishes a full 360∘ transmission phase while upholding a 1-dB transmission loss, with an overall thickness measuring 3.4 mm (equivalent to 0.34λ0 at 30.0 GHz). Its balanced unit cell arrangement amplifies its effectiveness in applications involving dual polarization. We examine the transmitarray behavior across four OAM modes (+1, +2, +3, +4 ), unveiling notable mode purity at operating frequency. Specifically, a broadband OAM vortex beam is achieved for the +1 mode during simulation. A square aperture transmitarray fed by a horn antenna is fabricated and measured to validate these simulated findings. Experimental results confirm the successful broadband vortex beam generation for $l = +1$ mode across the frequency spectrum from 27.0 to 40.0 GHz, approximately 43.3%. Additionally, the proposed transmitarray achieves a peak gain of 21.7 dBi, accompanied by an 11.8% aperture efficiency. Noteworthy is the consistent maintenance of mode purity above 86%.
In this paper, a large, compact array antenna that can be expanded in the 2-D plane is proposed for near-field radio frequency identification applications. By the introduction of the fractal structure and corner joint method, the array is easy to expand in the 2-D plane. An antenna element can be divided into a dozen or so loops, and traveling wave distribution makes sure that every loop is excited in a time period. So that a strong and uniform magnetic field could be generated in a large area. As a proof of concept, array antennas with $1 \times 8$, $2 \times 4$, and $3 \times 3$ elements are designed, fabricated, and measured. The measured bandwidth of the antennas covers the entire Chinese standard. Reading distances of the proposed large array antennas achieved up to 57 mm. Results show that the proposed antenna could realize flexibility and extendibility in a large area with stable and uniform magnetic field distribution.
The evolutionary process of mixing induced by Rayleigh–Taylor (RT) and Richtmyer–Meshkov (RM) instabilities typically progresses through three stages: initial instability growth, subsequent mixing transition and ultimate turbulent mixing. Accurate prediction of this entire process is crucial for both scientific research and engineering applications. For engineering applications, Reynolds-averaged Navier–Stokes (RANS) simulation stands as the most viable method currently. However, it is noteworthy that existing RANS mixing models are primarily tailored for the fully developed turbulent mixing stage, rendering them ineffective in predicting the crucial mixing transition. To address that, the present study proposes a RANS mixing transition model. Specifically, we extend the idea of the intermittent factor, which has been widely employed to integrate with turbulence models for predicting boundary layer transition, to mixing problems. Based on a high-fidelity simulation of a RT case, the intermittent factor defined based on enstrophy is extracted and then applied to RANS calculations, showing that it is possible to accurately predict mixing transition by introducing the intermittent factor to the turbulence production from the baseline K-L turbulence mixing model. Furthermore, to facilitate practical predictions, a transport equation has been established to model the spatio-temporal evolution of the intermittent factor. Coupled with the K-L model, the intermittent factor provided by the transport equation is applied to modify the Reynolds stress in RANS calculations. Thereafter, the present transition model has been validated in a series of tests, demonstrating its accuracy and robustness in the capturing mixing process in different types and stages of interfacial mixing flows.
Stimulated Raman scattering is a third-order nonlinear optical effect that is not only effective for wavelength converting laser output, but also for single longitudinal-mode output due to the absence of spatial hole burning. Diamond is a prominent Raman-active medium that has significant potential for linewidth narrowing and wavelength converting lasers at high power levels due to its high thermal conductivity, long Raman frequency shift and wide spectral transmission range. In this work we utilize diamond in a resonantly mode-matched external cavity to achieve cascaded Raman conversion of a 1064 nm laser. By fine-tuning the length of this external cavity, we can obtain narrow linewidth emission at 1240 and 1485 nm. When operating at maximum power, the measured linewidths were more than twofold narrower than the linewidth of the fundamental field. In addition, the noise levels of the Stokes fields are lower than that of the fundamental field throughout the entire noise frequency range, and the intrinsic linewidth of the second Stokes field, which is expressed at the hertz level (~3.6 Hz), is decreased by approximately three orders of magnitude compared to that of the pump. This work represents the first measurement and analysis of the linewidth and noise characteristics of cascaded diamond Raman lasers and, significantly, offers a new means by which high-power, narrow linewidth laser output can be produced from wavelength-converted laser systems.
Despite global efforts to end tuberculosis (TB), the goal of preventing catastrophic health expenditure (CHE) due to TB remains unmet. This cross-sectional study was conducted in Guizhou Province, Southwest China. Data were collected from the Hospital Information System and a survey of TB patients who had completed standardized antituberculosis treatment between January and March 2021. Among the 2 283 participants, the average total expenditure and out-of-pocket expenditure were $1 506.6 (median = $760.5) and $683.6 (median = $437.8), respectively. Health insurance reimbursement reduced CHE by 16.8%, with a contribution rate of 24.9%, and the concentration index changed from -0.070 prereimbursement to -0.099 postreimbursement. However, the contribution of health insurance varied significantly across different economic strata, with contribution rates of 6.4% for the lowest economic group and 53.1% for the highest group. For patients from lower socioeconomic strata, health insurance contributed 10.7% to CHE in the prediagnostic phase and 23.5% during treatment. While social health insurance alleviated the financial burden for TB patients, it did not provide sufficient protection for those in lower economic strata or during the prediagnostic stage. This study underscores the need for more effective and equitable subsidy policies for TB patients .
In this paper, a high-order-mode (HOM) (TE330) cavity-fed 45° linear polarized 6×6 slot array antenna is proposed. The 45° linear polarization is achieved by introducing asymmetric cross slots on the HOM cavity, resulting in low profile and wide bandwidth. The antenna array was verified using standard printed circuit board technology. Measured results show that the impedance bandwidth ( $|S_{11}|\le$ −10 dB) is 13.9% (36.98–42.92 GHz), and the peak gain is 19.3 dBi with a 3-dB gain bandwidth of 13.6%. Attributed to its simple structure, low profile, and wide bandwidth, the presented antenna is a good candidate for 5G applications.
X-ray frequency combs (XFCs) are of great interest in many scientific research areas. In this study, we investigate the generation of high-power tunable XFCs at the Shanghai soft X-ray Free-Electron Laser facility (SXFEL). To achieve this, a chirped frequency-beating laser is employed as the seed laser for echo-enabled harmonic generation of free-electron lasers. This approach enables the formation of an initial bunching of combs and ultimately facilitates the generation of XFCs under optimized conditions. We provide an optical design for the chirped frequency-beating seed laser system and outline a method to optimize and set the key parameters that meets the critical requirements for generating continuously tunable XFCs. Three-dimensional simulations using realistic parameters of the SXFEL demonstrate that it is possible to produce XFCs with peak power reaching 1.5 GW, central photon energy at the carbon K edge (~284 eV) and tunable repetition frequencies ranging from 7 to 12 THz. Our proposal opens up new possibilities for resonant inelastic X-ray scattering experiments at X-ray free-electron laser facilities.
Ceratopsian dinosaurs underwent great changes, including a shift of locomotion mode, enlarged horns and frills, and increased body size. These changes occur alongside the evolution of endocranial morphology and physiology such as the size and shape of the flocculus, hearing range, olfactory ratio, and the reptile encephalization quotient (REQ). However, the evolution of endocranial structures in early ceratopsians is still unclear because of a lack of information on the earliest ceratopsians. Here, we reconstructed the endocasts of three early-diverging ceratopsians including the Late Jurassic Yinlong, and the Early Cretaceous Liaoceratops and Psittacosaurus. These ceratopsians display obvious flocculi, large and separate olfactory bulbs, long and high anterior semicircular canals, and relatively long cochlear ducts. In the evolution of the earliest ceratopsians to early neoceratopsians, changes include the increasing size of the flocculus (which is reduced or absent in late-diverging ceratopsids), the attenuation of the semicircular canals, and the heightening of the anterior semicircular canal (which is shortened in late-diverging ceratopsids). The endocranial structures suggest early-diverging ceratopsians had a higher olfactory acuity and were adapted to hearing higher frequencies than late-diverging ceratopsians. Furthermore, the REQ suggests that Yinlong and Psittacosaurus were more highly encephalized than late-diverging ceratopsians and most extant reptiles. The angle of the lateral semicircular canal suggests that heads in ceratopsians display a transition from a forward posture to a more downward posture. Our new findings are significant for understanding the physiological changes during ceratopsian evolution and also have implications for the evolution of physiology in extant tetrapods.
The formation and evolution of unconfined counter-helicity spheromaks merging have been experimentally investigated by using a magnetized coaxial plasma gun. By comparing the time-dependent photodiode signals and plasma radiation images of counter-helicity spheromaks merging and plasma jets merging, it is found that the field-reversed configuration (FRC) plasma formed by counter-helicity spheromaks merging has a distinct contour and a long maintenance time. For plasma jets merging, the resulting plasma has no discernible contours and a shorter lifetime. In addition, it is inferred from these data that stagnation heating and magnetic reconnection events occur during the counter-helicity spheromaks merging, causing a rapid rise in plasma pressure at the merging midplane and sharp kinks in the field lines near the merger region. By changing different operating parameters and observing the impact on the merger characteristics, it is suggested that the qualitative dynamics of the FRC plasma depends on the balance between the plasma pressure and the magnetic pressure. The high discharge voltage breaks the equilibrium in the merged body, while the large gas-puffed mass just weakens the compression effect of the merged body. These results give us an intuitive understanding of the counter-helicity spheromak merger process and its dependence on discharge parameters, and also provide a distinct perspective for the optimal design of FRC.
Sjögren's syndrome (SS) is a chronic autoimmune disease caused by immune system disorders. The main clinical manifestations of SS are dry mouth and eyes caused by the destruction of exocrine glands, such as the salivary and lacrimal glands, and systemic manifestations, such as interstitial pneumonia, interstitial nephritis and vasculitis. The pathogenesis of this condition is complex. However, this has not been fully elucidated. Treatment mainly consists of glucocorticoids, disease-modifying antirheumatic drugs and biological agents, which can only control inflammation but not repair the tissue. Therefore, identifying methods to regulate immune disorders and repair damaged tissues is imperative. Cell therapy involves the transplantation of autologous or allogeneic normal or bioengineered cells into the body of a patient to replace damaged cells or achieve a stronger immunomodulatory capacity to cure diseases, mainly including stem cell therapy and immune cell therapy. Cell therapy can reduce inflammation, relieve symptoms and promote tissue repair and regeneration of exocrine glands such as the salivary glands. It has broad application prospects and may become a new treatment strategy for patients with SS. However, there are various challenges in cell preparation, culture, storage and transportation. This article reviews the research status and prospects of cell therapies for SS.
ADP-ribosylation (ADPRylation), which encompasses poly(ADP-ribosyl)ation and mono(ADP-ribosyl)ation, is an important post-translational modification catalysed by the poly(ADP-ribose) polymerase (PARP) enzyme superfamily. The process involves writers (PARPs) and erasers (ADP-ribose hydrolases), which work together to precisely regulate diverse cellular and molecular responses. Although the PARP-mediated synthesis of ADP-ribose (ADPr) has been well studied, ADPr degradation by degrading enzymes deserves further investigation. Nonetheless, recent studies have provided important new insights into the biology and functions of ADPr hydrolases. Notably, research has illuminated the significance of the poly(ADP-ribose) degradation pathway and its activation by the coordinated actions of poly(ADP-ribose) glycohydrolase and other ADPr hydrolases, which have been identified as key components of ADPRylation signalling networks. The degradation pathway has been proposed to play crucial roles in key cellular processes, such as DNA damage repair, chromatin dynamics, transcriptional regulation and cell death. A deep understanding of these ADPr erasing enzymes provides insights into the biological roles of ADPRylation in human health and disease aetiology and paves the road for the development of novel therapeutic strategies. This review article provides a summary of current knowledge about the biochemical and molecular functions of ADPr erasers and their physiological implications in human pathology.
Milk fat is a high-value component of the U.S. dairy market. It is the major energy component of milk and is responsible for many organoleptic and technological characteristics of milk and dairy products. In addition, milk fat is unquestionably distinctive among all dietary fats that humans consume, as it is not only comprised of several hundred different fatty acids (FAs) but also contains a wide and unique array of bioactive lipids. Milk fat is dispersed in milk primarily in the form of fat globules. These cytoplasmic lipid droplets originate from mammary epithelial cells (MECs) and are secreted into the alveolar lumen surrounded by a membrane. Many advances in our knowledge of specific enzymes involved in milk lipid synthesis, the selectivity of the triacylglyceride (TAG) synthesis enzymes for specific FAs, the molecular mechanisms behind the uptake of long-chain FAs into the cells and the milk lipid secretion process have led to an improved understanding of the biology of milk fat synthesis. However, research to provide deeper insights into the mechanism of lipid synthesis in MECs is warranted and might lead to novel strategies to alter milk fat content and quality to benefit the dairy industry and meet dietary recommendations and consumer demands for foods that positively impact health. In this review, we aimed to provide a general overview of our current knowledge of the molecular aspects of milk lipid synthesis in MECs, from the uptake of blood-derived precursors to the intracellular formation of TAG-rich fat droplets secreted into milk as milk fat globules. We also highlight some current gaps in the knowledge that warrant further exploration. Given the importance of dairy food in the human diet, a better understanding of these processes could help develop novel strategies to alter milk fat composition in ways that benefit both human health and dairy producers.
Background: A key efficacy indicator in generalized myasthenia gravis (gMG) treatment is improvement in MG-ADL score. Minimal symptom expression (MSE, MG-ADL total score of 0 or 1) is explored as a novel proposed treatment target in gMG in the phase 3 study of intravenous efgartigimod, ADAPT, and its open-label extension, ADAPT+. Methods: Post hoc analyses of acetylcholine receptor antibody positive participants in ADAPT (n=129) and ADAPT+ (n=111) were performed. Results: In ADAPT, 44.6% receiving efgartigimod achieved MSE vs 10.9% of participants given placebo. Despite less frequent assessment during ADAPT+, 40.5% of participants achieved MSE. Eighty-one percent of participants treated with efgartigimod who achieved MSE in ADAPT also achieved MSE during ADAPT+; 23% who had not achieved MSE in ADAPT did in ADAPT+. Achieving MSE was associated with substantial improvements in QMG, MGC, MG-QoL15r, and EQ-5D-5L mean scores of 11.4, 16.0, 12.4, and 0.3 points, respectively, from baseline to best score (across all visits). These drastic improvements resulted in quality of life (QoL) comparable to that of healthy populations. MSE achievement also resulted in sustained improvements in these disease-specific and QoL measures. Conclusions: Participants who achieved MSE showed substantial and consistent improvements across multiple disease measures and experienced QoL comparable to that of healthy populations.
Autoimmune diseases are pathological autoimmune reactions in the body caused by various factors, which can lead to tissue damage and organ dysfunction. They can be divided into organ-specific and systemic autoimmune diseases. These diseases usually involve various body systems, including the blood, muscles, bones, joints and soft tissues. The transient receptor potential (TRP) and PIEZO receptors, which resulted in David Julius and Ardem Patapoutian winning the Nobel Prize in Physiology or Medicine in 2021, attracted people's attention. Most current studies on TRP and PIEZO receptors in autoimmune diseases have been carried out on animal model, only few clinical studies have been conducted. Therefore, this study aimed to review existing studies on TRP and PIEZO to understand the roles of these receptors in autoimmune diseases, which may help elucidate novel treatment strategies.
This paper retrospectively analysed the prevalence of macrolide-resistant Mycoplasma pneumoniae (MRMP) in some parts of China. Between January 2013 and December 2019, we collected 4,145 respiratory samples, including pharyngeal swabs and alveolar lavage fluid. The highest PCR-positive rate of M. pneumoniae was 74.5% in Beijing, the highest resistance rate was 100% in Shanghai, and Gansu was the lowest with 20%. The highest PCR-positive rate of M. pneumoniae was 74.5% in 2013, and the highest MRMP was 97.4% in 2019; the PCR-positive rate of M. pneumoniae for adults in Beijing was 17.9% and the MRMP was 10.48%. Among the children diagnosed with community-acquired pneumonia (CAP), the PCR-positive and macrolide-resistant rates of M. pneumoniae were both higher in the severe ones. A2063G in domain V of 23S rRNA was the major macrolide-resistant mutation, accounting for more than 90%. The MIC values of all MRMP to erythromycin and azithromycin were ≥ 64 μg/ml, and the MICs of tetracycline and levofloxacin were ≤ 0.5 μg/ml and ≤ 1 μg/ml, respectively. The macrolide resistance varied in different regions and years. Among inpatients, the macrolide-resistant rate was higher in severe pneumonia. A2063G was the common mutation, and we found no resistance to tetracycline and levofloxacin.
Genes involved in melanin production directly impact insect pigmentation and can affect diverse physiology and behaviours. The role these genes have on sex behaviour, however, is unclear. In the present study, the crucial melanin pigment gene black was functionally characterised in an urban pest, the German cockroach, Blattella germanica. RNAi knockdown of B. germanica black (Bgblack) had no effect on survival, but did result in black pigmentation of the thoraxes, abdomens, heads, wings, legs, antennae, and cerci due to cuticular accumulation of melanin. Sex-specific variation in the pigmentation pattern was apparent, with females exhibiting darker coloration on the abdomen and thorax than males. Bgblack knockdown also resulted in wing deformation and negatively impacted the contact sex pheromone-based courtship behaviour of males. This study provides evidence for black function in multiple aspects of B. germanica biology and opens new avenues of exploration for novel pest control strategies.
The present paper is concerned with the infimum of the norm of potentials for Sturm–Liouville eigenvalue problems with Dirichlet boundary condition such that the first two eigenvalues are known. The explicit quantity of the infimum is given by the two eigenvalues.
Oxidative stress is a risk factor for mammary health, resulting in decreased milk yield and milk quality. Application of exogenous bioactive compounds has been a research focus of antioxidation of animals in the mammary gland. Quercetin is a flavonoid extracted from vegetables, fruits and tea and has been shown to have a variety of biological activities, but the effect of quercetin on redox imbalance in mammary epithelial cells is unclear. In this study, cells of HC11, a mouse mammary epithelial cell line, were treated with quercetin, and the effects and molecular mechanisms of quercetin protection on hydrogen peroxide-induced oxidative stress were studied. Results showed that 20 μΜ quercetin attenuated hydrogen peroxide-induced lactate dehydrogenase release and reactive oxygen species (ROS) accumulation and alleviated the reduction of cell viability and antioxidant capacity. Quercetin significantly restored the activation of mitogen-activated protein kinase (MAPK) and nuclear factor E2-related factor 2 (Nrf2) pathways induced by hydrogen peroxide. Importantly, the inhibitors of p38 MAPK and extracellular regulated protein pathways affected the activation of Nrf2 pathway. All inhibitors of MAPK and Nrf2 pathways reduced the protective effects of quercetin on cell proliferation, the activity of catalase and the expression of glutamate-cysteine ligase modifier subunit. Meanwhile, the effects of quercetin on the production of ROS and expression of glutamate/cystine reverse transporter light chain were mainly dependent on Nrf2 pathway. In summary, the protective effect of quercetin in mammary epithelial cells was mediated via MAPK and Nrf2 pathways.