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Rumen methane emissions (RMEs) significantly contribute to global greenhouse gas emissions, underscoring the essentials to identify effective inhibitors for RME mitigation. Despite various inhibitors shown potential in reducing RME by modulating rumen microbes, their impacts include considerable variations and inconsistency.

Foam cells are primarily formed through scavenger receptors that mediate the uptake of various modified low-density lipoproteins (LDL) into cells. In addition to the receptor-dependent pathway, macropinocytosis is an essential nonreceptor endocytic pathway for vascular smooth muscle cells (VSMCs) to take up lipids. However, the molecular mechanisms underlying this process remain unclear. Primary cultured VSMCs were stimulated with 200 ng/mL lipopolysaccharide (LPS) and 200 µg/mL native LDL (nLDL). We observed a significant increase in Toll-like receptor 4 (TLR4) protein expression and a significant activation of macropinocytosis, which correlated with the highest uptake of nLDL and intracellular lipid deposition in WT VSMCs. However, macropinocytosis was inhibited and lipid accumulation decreased after treatment with macropinocytosis inhibitors and Syk inhibitors in WT VSMCs. Consistently, TLR4 knockout significantly suppressed macropinocytosis and lipid droplets accumulation in VSMCs. Taken together, our findings suggest a critical role of TLR4/Syk signaling in promoting receptor-independent macropinocytosis leading to VSMC-derived foam cells formation.Graphical AbstractThe activation of the macropinocytosis pathway triggered by TLR4/Syk induced by lipopolysaccharide (LPS) can enhance the uptake of native low-density lipoproteins (nLDL) and promote vascular smooth muscle cell (VSMC)-derived foam cells formation.

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The recent advances of deep learning in various mobile and Internet-of-Things applications, coupled with the emergence of edge computing, have led to a strong trend of performing deep learning inference on the edge servers located physically close to the end devices. This trend presents the challenge of how to meet the quality-of-service requirements of inference tasks at the resource-constrained network edge, especially under variable or even bursty inference workloads. Solutions to this challenge have not yet been reported in the related literature. In the present paper, we tackle this challenge by means of workload-adaptive inference request scheduling: in different workload states, via adaptive inference request scheduling policies, different models with diverse model sizes can play different roles to maintain high-quality inference services. To implement this idea, we propose a request scheduling framework for general-purpose edge inference serving systems. Theoretically, we prove that, in our framework, the problem of optimizing the inference request scheduling policies can be formulated as a Markov decision process (MDP). To tackle such an MDP, we use reinforcement learning and propose a policy optimization approach. Through extensive experiments, we empirically demonstrate the effectiveness of our framework in the challenging practical case where the MDP is partially observable.

Migrant workers are the key group of employment work. Promoting the employment transformation of migrant workers under the background of the booming digital economy and the deepening aging degree is related to the overall stability of employment, but also to rural revitalization and common prosperity. This paper uses five waves of data from the China Family Panel Studies (CFPS) from 2012 to 2020 to explore the impact of the aging of the labor force on the employment transformation of migrant workers using multiple Logit regression models, and systematically and deeply explores the role of the digital economy in this process and its mechanism. The main findings of this study are as follows: firstly, the aging of the labor force significantly inhibits the employment transformation of migrant workers, which is mainly reflected in the inhibition of their transformation from traditional industries to new economy industries. Secondly, the digital economy significantly promotes the employment transformation of migrant workers and effectively alleviates the inhibitory effect of the aging of the labor force on the employment transformation of migrant workers. And it mainly plays its role by promoting the industrial structure upgrading, and the social capital and human capital accumulation of migrant workers. Thirdly, the mitigation effect of the digital economy is more effective among high-skilled migrant workers, young and middle-aged migrant workers, rural migrant workers, as well as migrant workers in eastern cities, large-sized cities, and cities with high digital development levels. Based on the above research conclusions, this article proposes relevant policy recommendations for actively responding to the aging of the labor force and fully leveraging the mitigating effects of the digital economy.

The microstructures and corrosion behaviors of as-cast, T4-treated, and T6-treated Mg-6Gd-3Y-0.5Zr alloys were systematically investigated by SEM, TEM, immersion test, and electrochemical corrosion test. The results show that the microstructure of the as-cast alloy is composed of α-Mg and Mg24(Gd, Y)5eutectic phase, and in T4-treated alloy, Mg24(Gd, Y)5phase dissolves into the α-Mg matrix, leading to an increase in the (Y, Gd)H2phase. After T6 treatment, nanoscale Mg24(Gd, Y)5phase dispersedly precipitates from the α-Mg matrix, and exhibits a specific orientation relationship with the α-Mg:(332)Mg24(Gd,Y)5//(101¯1)α-Mg,[1¯3¯6]Mg24(Gd,Y)5//[1¯21¯0]α-Mg. The corrosion resistance of the Mg-6Gd-3Y-0.5Zr alloys can be ranked in the following order: T6-treated alloy exhibits the highest corrosion resistance, followed by the T4-treated alloy, and finally, the as-cast alloy. The corrosion products of the alloys are all composed of MgO, Mg(OH)2, Gd2O3, Y2O3, and MgCl2. The corrosion behavior of Mg-6Gd-3Y-0.5Zr alloy is closely related to the precipitated phase. By establishing the relationship between corrosion rate, hydrogen evolution rate, and corrosion potential, it is further demonstrated that during the micro galvanic corrosion process, the coarse Mg24(Gd, Y)5phase in the as-cast alloy undergoes extensive dissolution, and (Y, Gd)H2phase promotes the dissolution of the α-Mg matrix in the T4-treated alloy, intensifying the hydrogen evolution reaction. The T6-treated alloy, with dispersive precipitation of nanoscale Mg24(Gd, Y)5phase, exhibits better corrosion resistance performance.

This letter presents a low-cost ultrathin metal-only transmitarray (MOTA) antenna based on polarization rotation elements at X-Band. The unit-cell comprises only dual metal layers etched with a pair of perpendicularly orientated fan-shaped slits and separated by an air gap of 2 mm, featuring an ultrathin configuration of 0.067λ at 10 GHz. It twists the polarization of transmission wave orthogonally with regard to the incidence. By tuning the length of fan-shaped slits along with mirroring the bottom layer of the unit-cell, a 360° phase span and a high transmission magnitude are realized. To validate the design concept, an ultrathin MOTA accommodating 361 elements is fabricated and measured. In terms of testing results, 7% 1 dB gain bandwidth and 42% peak aperture efficiency are realized. Moreover, the sidelobe level and cross-polarization level are 22 and 25 dB at 10 GHz, respectively. In comparison with existing MOTAs, the proposed design features a remarkably lower profile with reduced fabrication complexity and cost while preserving a desirable overall performance. Furthermore, the proposed ultrathin unit-cell can also be adopted in a metal-only folded transmitarray for an even thinner and compact structure.

In this letter, a high-efficiency planar all-metal folded reflectarray adopting polarization conversion element with a continuous 360° phase is proposed. It contains three parts, a bottom planar reflectarray for polarization conversion and beam focus, a top grid polarizer for selection of polarization, and a feed horn for illumination, which are all implemented by metal. By varying bottom reflectarray element's geometrical dimensions as well as mirroring its structure, a linear and continuous 360° phase span is achieved, leading to a good phase compensation accuracy when designing the array. For proof of concept, an all-metal low-profile folded reflectarray composed of 625 elements is developed. The results from experiments reveal that the proposed design exhibits a high aperture efficiency of 62.4% with 1 dB/3 dB gain bandwidth of 12%/22%, respectively. These favorable features along with the low-profile all-metal configuration make the design very suitable for various high-gain communication systems.

Purpose: Depth estimation is the basis of 3D reconstruction of airway structure from 2D bronchoscopic scenes, which can be further used to develop a vision-based bronchoscopic navigation system. This work aims to improve the performance of depth estimation directly from bronchoscopic images by training a depth estimation network on both synthetic and real datasets. Methods: We propose a cGAN-based network Bronchoscopic-Depth-GAN (BronchoDep-GAN) to estimate depth from bronchoscopic images by translating bronchoscopic images into depth maps. The network is trained in a supervised way learning from synthetic textured bronchoscopic image-depth pairs and virtual bronchoscopic image-depth pairs, and simultaneously, also in an unsupervised way learning from unpaired real bronchoscopic images and depth maps to adapt the model to real bronchoscopic scenes. Results: Our method is tested on both synthetic data and real data. However, the tests on real data are only qualitative, as no ground truth is available. The results show that our network obtains better accuracy in all cases in estimating depth from bronchoscopic images compared to the well-known cGANs pix2pix. Conclusions: Including virtual and real bronchoscopic images in the training phase of the depth estimation networks can improve depth estimation’s performance on both synthetic and real scenes. Further validation of this work is planned on 3D clinical phantoms. Based on the depth estimation results obtained in this work, the accuracy of locating bronchoscopes with corresponding pre-operative CTs will also be evaluated in comparison with the current clinical status.

Raised intracranial pressure is a hallmark of cryptococcal meningitis and is associated with increased mortality. Continuous drainage of lumbar cerebrospinal fluid is suggested to control intracranial pressure. The complications induced [...]

A multipolarized metal-only reflectarray antenna (MPMORA) is proposed and investigated in this communication. The reflectarray is an all-metal planar structure and is composed of unit-cells featuring perpendicularly placed size-variable slots carved in a metal sheet. Owing to negligible interactions between orthogonal slots of the unit-cell, a multipolarized metal-only reflectarray with dual-linear and dual-circular operations can be realized by rotation of a linearly polarized (LP) feed with 0°, 45°, 90°, and 135°, respectively. For proof-of-concept, a prototype hosting 441 unit-cells and operating at X-band is manufactured and measured. The testing data reveals that the proposed design can achieve reasonable 1 dB gain drop bandwidths and peak aperture efficiencies for all polarizations, for instance, 15.3% and 45% in the case of right-hand circular polarization (RHCP). Moreover, the 3 dB axial ratio bandwidths for RHCP and left-hand circular polarization (LHCP) are also wide, which are 26% and 39%, respectively. These satisfactory behavior as well as the metal-only configuration make our design a competitive candidate for multi-polarization applications.

Metal sulfide anodes have aroused much attention in potassium ion batteries (PIBs) owing to their high theoretical capacities, but the sluggish kinetics and inferior cycling performance caused by severe volumetric change and particle pulverization greatly hinder their further development. Herein, robust hollow structure design together with phase structure engineering endow (Bi-Sb)2S3@N-C anode with superior (de)potassiation kinetics and excellent electrochemical performances in PIBs. Specifically, in situX-ray diffraction combined with density functional theory calculations and ex situX-ray photoelectron spectroscopy and high-resolution transmission electron microscopy (TEM) analyses indicated a fresh reaction mechanism of (Bi-Sb)2S3anode with a distinctive multistep (de)potassiation route along (003) plane of (Bi,Sb) alloy thanks to the Bi-Sb phase regulation in (Bi-Sb)2S3anode, ensuring it with superior reaction kinetics. Moreover, in situTEM characterization revealed the advantages of the hollow nanostructure with carbon shell, facilitating fast ion transport kinetics and high tolerance of volume change as well as enabling the structural integrity of electrode material during (de)potassiation. As a result, the (Bi-Sb)2S3hollow nanocube with N-doped carbon shell ((Bi-Sb)2S3@N-C) delivers a high initial Coulombic efficiency of 66.3%, a great rate performance of 289 mAh g–1at 2.0 A g–1, and an ultralong cycling life (89% retention after 220 cycles at 0.1 A g–1and 85% retention after 1600 cycles at 2.0 A g–1) in PIBs. Furthermore, the full cell of (Bi-Sb)2S3@N-C//PTCDA affords a high reversible capacity of 281 mA h g–1at 1.0 A g–1after 300 cycles. This work combines structural design and in situtechniques, proving a successful nanostructure engineering strategy to rationalize alloy-type electrode materials for PIBs.

The structural groups of 2-oxindole and tricyclic 3a-hydroxy-hexahydropyrrolo-[2,3-b]indole (HO-HPI) are important pharmacophores. Chemical synthesis of complex alkaloids containing a 2-oxindole or HO-HPI moiety, especially the latter one, has been a long-standing challenge. Herein, we characterized the P450 enzyme AfnD, and its homologue proteins, HmtT, ClpD, KtzM, and LtzR, as cyclopeptide 2-oxindole and HO-HPI monooxygenases (cpOPMOs) that could introduce a 2-oxindole or HO-HPI moiety into the tryptophan-containing cyclopeptides in a pH-dependent manner. A universal catalytic mechanism was proposed for the five cpOPMOs, in which two conserved residues, Asp and Ser (Thr for LtzR), were proposed to divergently open the epoxide intermediates, thereby forming a 2-oxindole or HO-HPI moiety. Based on this, we constructed ten Asp or Ser/Thr mutants of cpOPMOs, which could synthesize cyclopeptides with an HO-HPI or 2-oxindole structure, selectively, under appropriate reaction conditions. All of the ten cpOPMO mutants exhibited high substrate promiscuities and usually performed well with cyclopeptides that are structurally similar to their native substrates. Overall, our work discovers a group of intriguing P450 enzymes, the cpOPMOs, and provides a powerful enzymatic toolkit for the selective synthesis of HO-HPI- or 2-oxindole-containing cyclopeptides.

A single-layered broadband reflectarray antenna employing 0.15-wavelength elements is proposed and investigated in this letter. The unit cell is constituted by a ring patch inserted with an interior concave arm and arranged in a grid size of 4.5 mm × 4.5 mm, corresponding to only 0.15 wavelength at 10 GHz. Despite such a small grid spacing, a linear phase close to 360° can still be obtained by changing the height of the embedded concave arm, without adjusting the external ring size. A planar reflectarray antenna composed of 2116 unit cells is designed, manufactured, and tested. According to the measured results, the 1 dB gain bandwidth of the reflectarray antenna is 29%, while the peak aperture efficiency is 66%. Besides, satisfactory sidelobe and cross-polarization levels are also achieved. These promising features show a good overall performance of the proposed array and also successfully demonstrate the feasibility of employing 0.15-wavelength element for wideband reflectarray designs.

Abstract: High silicon aluminum alloy coatings (HSAACs) are characterized by high surface hardness and excellent wear resistance, and the fineness has a significant impact on their properties. In this study, Al–40Si–5Fe coating was prepared by supersonic plasma spraying using Al–35Si–4Fe powder as raw material. The coating contains a variety of strengthening structures such as amorphous, nanocrystalline and supersaturated solid solution. The average hardness of the coating reached up to 465.3 ± 24.4HV0.2, which was much higher than that of the Al–Si alloys/coatings prepared by various processes. Under the test conditions, the wear mechanism of the coating was dominated by fatigue wear with slight abrasive wear, and the wear rate was 1.88 × 10–4mm3/N. A large amount of refined Si phase in the oxide film on the worn surface effectively prevented the cracking and spalling of the oxide film. Graphical abstract:

A reflectarray antenna employing metal-only polarization rotation elements is proposed in this letter. The element is composed of double metallic layers separated by an air gap and rotates the reflection wave polarization orthogonally with respect to that of the incidence wave. By tuning the structural dimension, a pair of elements with 90° phase difference are obtained. These two elements together with their mirroring images can be employed as a 2-bit phase shifter with 0°, 90°, 180°, and 270° phase shift from 9 to 10.8 GHz. For proof-of-concept, a metal-only reflectarray containing 225 unit-cells is developed and tested. According to experimental results, the 1 dB and 3 dB gain bandwidth of the metal-only reflectarray are 19% and 38% respectively while the peak aperture efficiency is 34%. These encouraging features demonstrate that reflectarrays can be successfully designed with metal-only polarization rotation elements and present a good potential for space applications.

Influenza polymerase (FluPol) transcribes viral mRNA at the beginning of the viral life cycle and initiates genome replication after viral protein synthesis. However, it remains poorly understood how FluPol switches between its transcription and replication states, especially given that the structural bases of these two functions are fundamentally different. Here we propose a mechanism by which FluPol achieves functional switching between these two states through a previously unstudied conformation, termed an ‘intermediate state’. Using cryo-electron microscopy, we obtained a structure of the intermediate state of H5N1 FluPol at 3.7 Å, which is characterized by a blocked cap-binding domain and a contracted core region. Structural analysis results suggest that the intermediate state may allow FluPol to transition smoothly into either the transcription or replication state. Furthermore, we show that the formation of the intermediate state is required for both the transcription and replication activities of FluPol, leading us to conclude that the transcription and replication cycles of FluPol are regulated via this intermediate state.

This letter presents a metal-only folded reflectarray antenna, consisting of three components, namely a pyramidal feed horn, a lower reflectarray, and an upper polarizer, which are all made of metal. The lower reflectarray consisting of planar polarization rotation elements focuses the beam and twists the incoming wave polarization perpendicularly so that the reflection wave can pass through the upper polarizer. With the adjustment of geometrical size, four elements with an equal phase interval of 45° are achieved. In addition, along with their mirror counterparts, 3-bit phase shifting elements covering 0°, 45°, 90°, 135°, 180°, 225°, 270°, and 315° within 9–10.6 GHz can be realized. For validation, a metal-only folded reflectarray with 610 elements is built and tested. Based on experiment results, 1 dB gain bandwidth is 16% while the peak aperture efficiency is 45%. These promising properties together with the low-profile metal-only structure make the proposed design a great candidate for space applications.

Purpose: Synthetic realistic-looking bronchoscopic videos are needed to develop and evaluate depth estimation methods as part of investigating vision-based bronchoscopic navigation system. To generate these synthetic videos under the circumstance where access to real bronchoscopic images/image sequences is limited, we need to create various realistic-looking image textures of the airway inner surface with large size using a small number of real bronchoscopic image texture patches. Methods: A generative adversarial networks-based method is applied to create realistic-looking textures of the airway inner surface by learning from a limited number of small texture patches from real bronchoscopic images. By applying a purely convolutional architecture without any fully connected layers, this method allows the production of textures with arbitrary size. Results: Authentic image textures of airway inner surface are created. An example of the synthesized textures and two frames of the thereby generated bronchoscopic video are shown. The necessity and sufficiency of the generated textures as image features for further depth estimation methods are demonstrated. Conclusions: The method can generate textures of the airway inner surface that meet the requirements for the texture itself and for the thereby generated bronchoscopic videos, including “realistic-looking,” “long-term temporal consistency,” “sufficient image features for depth estimation,” and “large size and variety of synthesized textures.” Besides, it also shows advantages with respect to the easy accessibility to required data source. A further validation of this approach is planned by utilizing the realistic-looking bronchoscopic videos with textures generated by this method as training and test data for some depth estimation networks.

Diabetic cardiomyopathy (DCM), which occurs in patients with diabetes, carries a substantial risk concerning the subsequent development of heart failure and increased mortality (1). Different pathophysiological stimuli are involved in [...], OBJECTIVE--Tribbles 3 (TRB3) is associated with insulin resistance, an important trigger in the development of diabetic cardiomyopathy (DCM). We sought to determine whether TRB3 plays a major role in modulating DCM and the mechanisms involved. RESEARCH DESIGN AND METIIODS--The type 2 diabetic rat model was induced by high-fat diet and low-dose streptozotocin. We evaluated the characteristics of type 2 DCM by serial echocardiography and metabolite tests, Western blot analysis for TRB3 expression, and histopathologic analyses of cardiomyocyte density, lipids accumulation, cardiac inflammation, and fibrosis area. We then used gene silencing to investigate the role of TRB3 in the pathophysiologic features of DCM. RESULTS--Rats with DCM showed severe insulin resistance, left ventricular dysfunction, aberrant lipids deposition, cardiac inflammation, fibrosis, and TRB3 overexpression. We found that the silencing of TRB3 ameliorated metabolic disturbance and insulin resistance; myocardial hypertrophy, lipids accumulation, inflammation, fibrosis, and elevated collagen I-to-III content ratio in DCM rats were significantly decreased. These anatomic findings were accompanied by significant improvements in cardiac function. Furthermore, with TRB3 gene silencing, the inhibited phosphorylation of Akt was restored and the increased phosphorylation of extracellular signal-regulated kinase 1/2 and Jun N[H.sub.2]-terminal kinase in DCM was significantly decreased. CONCLUSIONS--TRB3 gene silencing may exert a protective effect on DCM by improving selective insulin resistance, implicating its potential role for treatment of human DCM. Diabetes 60:2963-2974, 2011

Glutaric aciduria type I (GA-I) is an autosomal recessive genetic disorder caused by a deficiency in glutaryl-CoA dehydrogenase (GCDH). Patients who do not receive proper treatment may die from acute encephalopathic crisis. Current treatments for GA-I include a low-lysine diet combined with oral supplementation of L-carnitine. A mouse model of Gcdhc.422_428del/c.422_428del(Gcdh−/−) was generated in our laboratory using CRISPR/Cas9. Gcdh−/−mice had significantly higher levels of glutaric acid (GA) in the plasma, liver, and brain than those in wild-type C57BL/6 mice. When given a high-protein diet (HPD) for two days, approximately 60% of Gcdh−/−mice did not survive the metabolic stress. To evaluate whether GCDHgene replacement therapy could be used to provide sustained treatment for patients with GA-1, we prepared a recombinant adeno-associated virus (rAAV) carrying a human GCDHexpression cassette and injected it into Gcdh−/−neonates for a proof-of-concept (PoC) study. Our study demonstrated that delivering rAAV to the central nervous system (CNS), but not the peripheral system, significantly increased the survival rate under HPD exposure. Our study also demonstrated that rAAVPHP.eB mediated a higher efficiency than that of rAAV9 in increasing the survival rate. Surviving mice showed dose-dependent GCDH protein expression in the CNS and downregulation of GA levels. Our study demonstrated that AAV-based gene replacement therapy was effective for GA-I treatment and provided a feasible solution for this unmet medical need.

There are problems in rural energy consumption, such as extensive management, poor economy and high gas emission. A multi-objective operation optimization method is proposed, in this paper, to solve the problems of economic and environmental protection operation of rural decentralized integrated energy system. The basic structure of rural decentralized integrated energy system was studied. The energy system was composed of solar collector, air source heat pump, heat storage water tank and electric boiler, which is composed of solar energy as the main energy source and air energy as the auxiliary energy source. A multi-objective operation optimization model of integrated energy system was constructed under the constraints of energy supply and demand balance and equipment capacity balance, taking economy and environmental protection as dual objectives. NSGA-II algorithm with dynamic congestion degree was selected to solve the optimization model. The economy and environmental protection of the optimized integrated energy heating system have been improved in the operation process through simulation analysis.

The effect of annealing temperature on the microstructure, mechanical property and anti-corrosion behavior of the X2CrNi12 ferritic stainless steel were systematically investigated. The results demonstrate that a large amount of (Fe, Cr)23C6precipitated at the ferrite grain boundaries after annealing below 740 °C. The precipitation of the (Fe, Cr)23C6was prevented with the increase of annealing temperature, and the martensite content gradually increased, which improved the tensile strength, yield strength, and hardness of the steels, while the elongation was decreased. The best comprehensive mechanical properties can be obtained at the annealing temperature of 850 °C and 950 °C. The ductile-dimple fracture is the primary fracture mode for the steels. The corrosion rates of the stainless steels first decreased and then increased with the increase of annealing temperature. The 770 °C-annealed steel has the best anti-corrosion ability. The corresponding corrosion mechanism can be attributed to the pitting corrosion induced by the (Fe, Cr)23C6and martensite. Moreover, the precipitation of (Fe, Cr)23C6could consume the Cr in the matrix and prevent the formation of passive film on the surface. And the phase transformation stress in the martensite can accelerate the local corrosion of the steel matrix.

The evaluation criteria for dosage of low-molecular-weight heparin (LMWH) for pregnant women at high risk of venous thromboembolism (VTE) remain unclear. A retrospective study was performed to investigate the relative appropriate LMWH administration strategy and dosage for pregnant women at risk of VTE. 219 pregnant women with perinatal and postpartum VTE were reviewed and divided into group A (fixed dose group: n=73, 5000?IU dalteparin daily for all women), group B (weight group: n=73, 2500?IU dalteparin daily for women less than 50?kg; 5000?IU dalteparin daily for women more than 50?kg), and group C (anti-factor Xa (FXa) + weight group: n=73, 5000?IU once daily for women less than 50?kg; 7500?IU once daily for women weighing 50–80?kg; 10,000?IU once daily for women weighing over 80?kg). Further dose administration was adjusted according to peak anti-FXa level, maintaining the peak at the 0.5–1.0?IU/mL range. Women in group C presented lower incidence of VTE and other pregnancy complications than group A and group B. Adjusting the dosage of LMWH according to both weight and anti-FXa level of pregnant women not only prevented VTE but also reduced the risk of postpartum hemorrhage induced by LMWH administration. In addition, adjusting the dose of LMWH according to anti-FXa level and body weight also affected the recurrence of VTE and the occurrence of postpartum hemorrhage in pregnant women.

Background: Healthy aging index (HAI) could predict adverse health consequences including mortality and disability independent of age and comorbidity. We investigated the role of HAI on trajectories of disability throughout later life based on a nationally representative sample. Methods: We examined 1733 participants aged over 60 years from the China Health and Retirement Longitudinal Study (CHARLS) followed for 7 years/4 waves repeatedly. Systolic blood pressure [SBP], cognitive function, cystatin C, peak expiratory flow [PEF], and fasting glucose were categorized using tertile or clinical reference range, and scored as 0 (healthiest), 1 (less healthy) and 2 (least healthy) respectively to further generate HAI summary scores (range 0–10). Disability was defined as the sum of impaired activities of daily living (ADL) and instrumental activities of daily living (IADL). We used linear mixed-effects model to study the association between HAI and trajectories of disability. Results: A total of 10.5% of participants represented in the healthiest group and 22.5% ended up as the least healthy. After adjusting for all potential confounders, disability progression was significantly faster (β= 0.27, 95% CI 0.11–0.42) in the least healthy group when comparing with the healthiest. Conclusion: Our findings suggest that HAI is associated with disability progression among adults aged over 60 years old. It might be beneficial for future interventions to specifically target older adults with high HAI scores as a means of reducing disability.

This study aimed to evaluate the stiffness of 2‐dimensional (2D) shear wave elastography (SWE) in preoperatively predicting the prognostic stage groups of invasive ductal carcinoma (IDC). Eighty‐six newly diagnosed lesions on 83 patients with IDCs were analyzed. All parameters from conventional ultrasound and stiffness to virtual touch tissue imaging and quantification were collected, and mean shear wave velocity (SWVmean) was calculated. Data on maximum diameter, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), histologic grading system and Tumor Node Metastasis (TNM) stages were collected. The levels of maximum shear wave velocity (SWVmax), minimum shear wave velocity (SWVmin) and SWVmean were compared. In receiver operating characteristic (ROC) curves analysis, the diagnostic efficacy was found in area under the curve (AUC). Parallel mode was used to improve the predictive value of sensitivity. The median stiffness of SWVmax and SWVmean for IDCs were 9.38 and 6.32 m/s for late stage (stages II, III, IV) and 6.39 m/s and 4.72 m/s for early stage (stage I) of the prognostic stage groups, respectively. The median stiffness values in the late stage were significantly higher than those in the early stage (P= .003, P= .005). The optimal cutoff stiffness of SWVmax and SWVmean were 8.62 and 6.13 m/s, respectively. In ROC curves analysis, the AUC for SWVmax was 0.742, and it showed a better diagnostic value than SWVmean (0.725). In predictive diagnosis, the sensitivity for SWVmax and SWVmean were both 62.50%. The parallel mode improved the prediction power of sensitivity to 68.75%. Preoperative SWV level may serve as a promising prognostic imaging indicator for breast IDCs.

Biological nitrogen fixation catalyzed by nitrogenase contributes greatly to the global nitrogen cycle. Nitrogenase expression is subject to regulation in response to nitrogen availability. However, the mechanism through which the transcriptional activator NifA regulates nitrogenase expression by interacting with PIInitrogen regulatory proteins remains unclear in diazotrophic proteobacteria lacking NifL. Here, we demonstrate that in Rhodopseudomonas palustrisgrown with ammonium, NifA bound deuridylylated PIIproteins to form an inactive NifA-PIIcomplex, thereby inhibiting the expression of nitrogenase. Upon nitrogen limitation, the dissociation of uridylylated PIIproteins from NifA resulted in the full restoration of NifA activity, and, simultaneously, uridylylation of the significantly up-regulated PIIprotein GlnK2 led to the increased expression of NifA in R. palustris. This insight into how NifA interacts with PIIproteins and controls nitrogenase expression sets the stage for creating highly efficient diazotrophs, reducing the need for energy-intensive chemical fertilizers and helping to diminish carbon emissions.

In this work, a new (Y, Gd)H2precipitate was identified and systematically investigated in the as-cast Mg-6Gd-3Y-0.5Zr alloy by XRD, SEM with EDS, TEM with EDS techniques and thermodynamics analysis. Results show that the as-cast alloy contains α-Mg, Mg24(Gd, Y)5, and (Y, Gd)H2phase. The (Y, Gd)H2phase usually forms near the eutectic phase Mg24(Gd, Y)5or in the α-Mg grains, displaying a rectangle-shape. The Mg24(Gd, Y)5and (Y, Gd)H2phases crystalize in bcc and fcc structure, respectively, and the (Y, Gd)H2phase has a semi-coherent relationship with α-Mg matrix. The thermodynamics calculation results reveal that the hydrogen dissolved in the melt leads to the formation of hydrides. It is also found that the (Y, Gd)H2hydride can form directly from the liquid phase during solidification. Additionally, it can precipitate by the decomposition of Mg24(Gd, Y)5phase due to absorbing hydrogen from the remaining melt.

Background: Icariin (ICA), one of the main effective components isolated from the traditional Chinese herb Epimedium brevicornu Maxim., has been reported to possess extensive pharmacological actions, including enhanced sexual function, immune regulation, anti-inflammation, and antiosteoporosis. Methods: Our study was designed to investigate the effect of ICA on cell proliferation and differentiation and the molecular mechanism of OPG/RANKL mediated by the Estrogen Receptor (ER) in hFOB1.19 human osteoblast cells. Results: The experimental results show that ICA can stimulate cell proliferation and increase the activity of Alkaline Phosphatase (ALP), Osteocalcin (BGP) and I Collagen (Col I) and a number of calcified nodules. Furthermore, the mRNA and protein expression of OPG and RANKL and the OPG/ RANKL mRNA and protein expression ratios were upregulated by ICA. The above-mentioned results indicated that the optimal concentration of ICA for stimulating osteogenesis was 50ng/mL. Subsequent mechanistic studies comparing 50ng/mL ICA with an estrogen receptor antagonist demonstrated that the effect of the upregulated expression is connected with the estrogen receptor. In conclusion, ICA can regulate bone formation by promoting cell proliferation and differentiation and upregulating the OPG/RANKL expression ratio by the ER in hFOB1.19 human osteoblast cells.

The microstructure and dry sliding wear performance of as-cast TiCp/Ti-1100-0.5Nb composite at 25 °C, 500 °C and 600 °C were systematically investigated. Results show that the solidification matrix microstructure is the typical Widmanstätten structure. The eutectic TiC particles are uniformly distributed in the matrix in the form of feathery, long rod and strip-like shapes. Meanwhile, the interface between TiC and titanium matrix is clear and without any reaction. The wear rate of TiCp/Ti-1100-0.5Nb at 600 °C and 500 °C is reduced by 95.8% and 79.9%, respectively, compared with that of the value of 51.8×10-6mm3·mm-1at 25 °C. The friction coefficient of the steady-state period at 25 °C, 500 °C, 600 °C is 0.48, 0.8, 1.2, respectively, and the variation extent of the friction coefficient at elevated temperatures is greater than at 25 °C. The wear mechanism is changed from the mixture of adhesive wear and abrasive wear to mild oxidation wear with rising temperature. It can also be concluded that the composite possesses excellent high temperature wear resistance. The high-wear resistance of the composite is attributed to the Fe2O3and TiO2. The presence of Fe2O3and TiO2reduces the wear rate, increases the friction coefficient, and also improves the range-ability of the friction coefficient.

Abstract

ABSTRACTRNase J is a prokaryotic 5′-3′ exo/endoribonuclease that functions in mRNA decay and rRNA maturation. Here, we report a novel duplex unwinding activity of mpy-RNase J, an archaeal RNase J from Methanolobus psychrophilus, which enables it to degrade duplex RNAs with hairpins up to 40 bp when linking a 5′ single-stranded overhangs of ≥ 7 nt, corresponding to the RNA channel length. A 6-nt RNA-mpy-RNase J-S247A structure reveals the RNA-interacting residues and a steric barrier at the RNA channel entrance comprising two archaeal loops and two helices. Mutagenesis of the residues key to either exoribonucleolysis or RNA translocation diminished the duplex unwinding activity. Substitution of the residues in the steric barrier yielded stalled degradation intermediates at the duplex RNA regions. Thus, an exoribonucleolysis-driven and steric occlusion-based duplex unwinding mechanism was identified. The duplex unwinding activity confers mpy-RNase J the capability of degrading highly structured RNAs, including the bacterial REP RNA, and archaeal mRNAs, rRNAs, tRNAs, SRPs, RNase P and CD-box RNAs, providing an indicative of the potential key roles of mpy-RNase J in pleiotropic RNA metabolisms. Hydrolysis-coupled duplex unwinding activity was also detected in a bacterial RNase J, which may use a shared but slightly different unwinding mechanism from archaeal RNase Js, indicating that duplex unwinding is a common property of the prokaryotic RNase Js.

Triple-negative breast cancer (TNBC), colon adenocarcinoma (COAD), ovarian cancer (OV), and glioblastoma multiforme (GBM) are common malignant tumors, in which significant challenges are still faced in early diagnosis, treatment, and prognosis. Therefore, further identification of genes related to those malignant tumors is of great significance for the improvement of management of the diseases. The database of the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) repository was used as the data source of gene expression profiles in this study. Malignant tumors genes were selected using a feature selection algorithm of maximal relevance and minimal redundancy (mRMR) and the protein–protein interaction (PPI) network. And finally selected 20 genes as potential related genes. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed on the potential related genes, and different tumor-specific genes and similarities and differences between network modules and pathways were analyzed. Further, using the potential cancer-related genes found above in this study as features, a support vector machine (SVM) model was developed to predict high-risk malignant tumors. As a result, the prediction accuracy reached more than 85%, indicating that such a model can effectively predict the four types of malignant tumors. It is demonstrated that such genes found above in this study indeed play important roles in the differentiation of the four types of malignant tumors, providing basis for future experimental biological validation and shedding some light on the understanding of new molecular mechanisms related to the four types of tumors.

Lipid metabolic deficiencies are associated with many genetic disorders. Bietti crystalline dystrophy (BCD), a blindness-causing inherited disorder with changed lipid profiles, is more common in Chinese and Japanese than other populations. Our results reveal that mouse models lacking Cyp4v3have less physiological and functional changes than those of BCD patients with this gene defect. After the administration of a high-fat diet (HFD), the occurrence of retinal lesions were both accelerated and aggregated in the Cyp4v3−/−mouse models, implying that changed lipid levels were not only associated factors but also risk factors to BCD patients. Facilitated by the results, we found that the reduced electroretinography waveforms and retinal thickness observed in the HFD-induced mouse models were effectively recovered after subretinal delivery of a human CYP4V2gene carried by an adeno-associated virus vector, which demonstrates the potential curability of BCD by gene therapy.

Perylene-3,4,9,10-tetracarboxylic dianhydride (PTCDA) has been intensively investigated for decades because of its unique electronic and optical properties and its applications in organic electronics and surface engineering and passivation of 2D materials. Recently, the high demand for achieving selective area deposition in device fabrications drives the research of utilizing organic molecules as a passivation layer on metals in the semiconductor industry. PTCDA molecules show promising potential to be used as a passivation layer on a metal surface because of their ability to form self-assembled compact lying-down layers with the well-exposed inert conjugated molecular π-plane. However, the thermal and chemical stabilities of monolayer PTCDA on metal surfaces have not been thoroughly studied. In this paper, we demonstrate that monolayer PTCDA on Cu(110) and Cu(111) surfaces exhibit good thermal and chemical stabilities, as revealed through the combination of in situX-ray photoelectron spectroscopy and in situlow-temperature scanning tunneling microscopy measurements. We show that monolayer PTCDA on copper is stable up to 220 °C and decomposes to perylene at higher temperature. Monolayer PTCDA also shows good chemical stability when exposed to O2and water, demonstrating good potential for its future applications as passivation layers in selective area deposition.

The falling ball tests were carried out on the Φ125 mm diameter Carbidic Austempered Ductile Iron (CADI) grinding balls with Mn content of 2.0wt.%, 2.3wt.%, 2.6wt.% and 3.0wt.%, respectively, and the kind of grinding ball with the most serious spalling was selected for stress simulation. The stress distribution between four grinding balls in the elbow of the falling ball test device when they collided with each other was simulated based on ANSYS. Results of the falling ball tests show that the spalling and mass loss of a CADI grinding ball increases with the increase of Mn content, and the CADI grinding ball with 3.0wt.% Mn shows the most obvious spalling and mass loss. The simulation results of stress distribution of a CADI grinding ball show that the maximum impact stress does not appear in the center of the contact area, but in the annular area (inner diameter of ∼20 mm and outer diameter of ∼50 mm) in the section with a depth of 5–15 mm below the grinding ball surface. The actual spalling of the ball is consistent with the simulation results, and the oxide-based impurities in CADI grinding ball accelerate the spalling of the grinding ball in service.

Mindfulness and self-compassion are reported to have a preventive effects on depression and anxiety disorders. In the present study, we aimed to assess the effect of mindful self-compassion intervention on preventing postpartum depression in a group of symptomatic pregnant women. Participants were screened and assigned to the intervention and control groups randomly. A 6-week Internet-based Mindful Self-Compassion Program was used to train the participants. Multiple scales were used to assess depressive and anxiety symptoms, mindfulness, self-compassion, and mother and infant well-being. All assessments were performed at three time points: baseline, 3 months, and 1 year postpartum. Compared with the control group, the intervention group showed significant improvement in depressive and anxiety behaviors. In addition, the intervention group became more mindful and self-compassionate at 3 months and 1 year postpartum. More importantly, both mothers and infants experienced substantial improvement in well-being. Our findings indicate that mindful self-compassion intervention is effective in preventing postpartum depression and promoting mother and infant well-being.

The abuse of antibiotics resulted in the emergence of antibiotics-resistant bacteria, which has raised a great social concern together with the impetus to develop effective antibacterial materials. Herein, the synthesis of biocompatible enzyme-responsive Ag nanoparticle assemblies (ANAs) and their application in the high-efficiency targeted antimicrobial treatment of methicillin-resistant Staphylococcus aureus(MRSA) have been demonstrated. The ANAs could collapse and undergo stable/collapsed transition on approaching MRSAbecause of the serine protease-like B enzyme proteins (SplB)-triggered decomposition of the branched copolymers which have been employed as the macrotemplate in the synthesis of responsive ANAs. This transition contributed greatly to the high targeting affinity and efficiency of ANAs to MRSA. The minimum inhibitory concentration and minimum bactericidal concentration against MRSAwere 2.0 and 32.0 μg mL–1, respectively. Skin wound healing experiments confirmed that the responsive ANAs could serve as an effective wound dressing to accelerate the healing of MRSAinfection.

CRISPR-based nucleic acid detection methods are reported to facilitate rapid and sensitive DNA detection. However, precise DNA detection at the single-base resolution and its wide applications including high-fidelity SNP genotyping remain to be explored. Here we develop a Cas12b-mediated DNA detection (CDetection) strategy, which shows higher sensitivity on examined targets compared with the previously reported Cas12a-based detection platform. Moreover, we show that CDetection can distinguish differences at the single-base level upon combining the optimized tuned guide RNA (tgRNA). Therefore, our findings highlight the high sensitivity and accuracy of CDetection, which provides an efficient and highly practical platform for DNA detection.

CRISPR-Cas12a/Cpf1, a single RNA-guided endonuclease system, provides a promising tool for genome engineering. However, only three Cas12a orthologs have been employed for mammalian genome editing, and the editing efficiency as well as targeting coverage still requires improvements. Here, we harness six novel Cas12a orthologs for genome editing in human and mouse cells, some of which utilize simple protospacer adjacent motifs (PAMs) that remarkably increase the targeting range in the genomes. Moreover, we identify optimized CRISPR RNA (crRNA) scaffolds that can increase the genome editing efficiency of Cas12a.

Objective This study aimed to retrospectively investigate the safety of ovarian preservation of premenopausal women with stage 1a endometrial carcinoma.Methods We performed a population-based study to identify surgically treated stage Ia endometrial cancer of premenopausal women who were diagnosed between August 1989 and December 2015 in our center. Survival outcomes and recurrence rate were examined for premenopausal women who underwent ovarian preservation. Recurrence-free survival rates were calculated following generation of Kaplan–Meier curves and were compared with the log-rank test. Cox regression analysis was performed to identify the independent factors affecting the recurrence rate.Results Patients with ovarian preservation tended to be significantly younger at diagnosis, have less myometrial invasion, and were less likely to undergo lymphadenectomy compared with women treated with bilateral salpingo-oophorectomy. There was no significant difference in recurrence-free survival between the two groups. In the Cox regression model, ovarian preservation remained an independent prognostic factor for improved overall survival.Conclusion Ovarian preservation does not have a negative effect on oncological outcomes. Ovarian preservation can be applied to premenopausal women with stage Ia endometrial carcinoma.

Peptide drugs are known for their high biological safety. However, compared with small molecule drugs, peptide drugs are easily oxidized and hydrolyzed as well as short in half-life. Herein, inspired by the long circulation of albumin in blood, we screened albumin binding peptides (ABPs) from a one-bead one-compound (OBOC) peptide library to increase the half-life of peptide drugs. Beads displaying random peptides were screened using fluorescent labeled human serum albumin. Fluorescent beads with specific binding to albumin were isolated for sequencing. The selected ABPs can effectively bind to albumin, thus possessing the long circulation of albumin. The dissociation constant (KD) of ABPs to albumin is up to 1 × 10−8 mol/L. Once one of ABPs (ABP2) was coupled to triptorelin, the circulation half-life of triptorelin in mice was significantly prolonged to 263.50 h much longer than that of triptorelin alone (179.07 h). In addition, the combination therapy using ABP-conjugated triptorelin and doxorubicin (DOX) can effectively inhibit the proliferation of tumor cells in mice. The OBOC screening strategy and resulting ABPs showed great potential for enhancing the delivery efficiency of peptide drugs.

Stainless steel clad plates are highly sought after in industries such as heavy machinery, ships, and pressure vessels. Intergranular corrosion, caused by the uphill diffusion of carbon atoms, hinders the progress of stainless steel composite plates. The controlled rolling and post-deformation of the solution-free treatment described in this paper inhibits the Segregation behavior of alloying elements, leading to increased resistance to intergranular corrosion and improved pitting corrosion ability in the 304/Q235 composites. The intergranular corrosion rate and corrosion potential of the 304/Q235 composites were 792 g/(m2·h) and −473.3 mVSCE, respectively, in their original hot rolled state. The introduction of high-density dislocations before the formation of chromium-rich carbides can hinder the precipitation of carbides along grain boundaries, resulting in an 18·3% reduction in the intergranular corrosion rate of the composite plate. Cold deformation is performed following the precipitation of chromium-rich carbides, resulting in a decrease in the degree of aggregation of C, Cr, and other elements. The aforementioned process described above results in a discontinuous distribution of carbides along grain boundaries, as well as the refinement and dissolution of the precipitation phase. The intergranular corrosion rate of the deformation-treated composite plate was reduced by 79 g/(m2·h) in comparison to its initial hot-rolled state. The aim of this study is to elucidate the underlying mechanism by which deformation influences the carbide precipitation behavior of stainless steel composite plates. This research provides a novel idea for the cost-effective and solution-free hot rolling preparation of stainless steel composite plates.

Idiopathic pulmonary fibrosis (IPF) is a chronic lethal disease in the absence of demonstrated efficacy for preventing progression. Although macrophage-mediated alveolitis is determined to participate in myofibrotic transition during disease development, the paradigm of continuous macrophage polarization is still under-explored due to lack of proper animal models. Here, by integrating 2.5 U/kg intratracheal Bleomycin administration and 10 Gy thorax irradiation at day 7, we generated a murine model with continuous alveolitis-mediated fibrosis, which mimics most of the clinical features of our involved IPF patients. In combination with data from scRNA-seq of patients and a murine IPF model, a decisive role of CCL2/CCR2 axis in driving M1 macrophage polarization was revealed, and M1 macrophage was further confirmed to boost alveolitis in leading myofibroblast activation. Multiple sticky-end tetrahedral framework nucleic acids conjunct with quadruple ccr2-siRNA (FNA-siCCR2) was synthesized in targeting M1 macrophages. FNA-siCCR2 successfully blocked macrophage accumulation in pulmonary parenchyma of the IPF murine model, thus preventing myofibroblast activation and leading to the disease remitting. Overall, our studies lay the groundwork to develop a novel IPF murine model, reveal M1 macrophages as potential therapeutic targets, and establish new treatment strategy by using FNA-siCCR2, which are highly relevant to clinical scenarios and translational research in the field of IPF.

GSK-3β is a versatile protein kinase participating in many reactions. Currently, there is insufficient understanding of its influence on breast cancer (BC). In order to explore its influence on migration and invasion in BC, we investigated its expression in BC cell lines using qRT-PCR and Western blot (WB). Immunohistochemistry (IHC) was used to examine the potential of GSK-3β to predict clinical outcome in BC patients. GSK-3β knockdown was achieved using an shRNA plasmid vector in T47D cells. Our research explored the biological reactions and downstream pathways involved. We found excessive GSK-3β expression in BC tissues, which was correlated with worse clinicopathological parameters and clinical outcome. Progression of BC was suppressed by GSK-3β knockdown. Furthermore, suppression of GSK-3β function led to a noticeable decrease in ATP generation, and this was associated with stimulation of AMP-activated protein kinase (AMPK) in T47D cells. Activation of AMPK, a typical sign of autophagy stimulation, was triggered after suppression of GSK-3β function, in parallel with increased generation of LC3 II. Our findings therefore indicate that GSK-3β participates in regulation of migration as well as stimulation of autophagy via mediating activation of the AMPK pathway. This suggests that GSK-3β has potential as a predictor of clinical outcome and as a target for BC therapy.

In this work, the substrate, NiCr coating, Al2O3coating with NiCr undercoating and Al2O3coating were tested by an impact indentation device equipped with an acoustic emission (AE) detection equipment. The surface morphology, dimension, cross-sectional image, 3D topography of indention and bonding strength of coatings were analyzed. The failure mechanism and AE signal characteristics of the coatings under impact were studied. The results demonstrate that the failure mode of NiCr coating was dominated by interface cracking, and that of Al2O3coating is fracture and accompanied by a small amount of interface cracking, while Al2O3coating with NiCr undercoating possesses common characteristics of the first two. The energy counting and wave voltage of AE signal were more sensitive to the bonding strength of coating in the impact process, which can be used to characterize the bonding strength of coating.