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Abstract As promising energy-storage devices, zinc–air batteries (ZABs) exhibit slow reaction kinetics for oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) occurring at their electrodes. High-performance bifunctional catalysts must thus be synthesized to accelerate the reversible conversion of oxygen and improve the rate and overall performance of ZABs. Herein, we reported the promising prospects of self-supported composite electrodes composed of wood-derived carbon (WDC) and bimetallic cobalt-iron alloys/oxides (CoFe-CoFe2O4@WDC) as efficient electrocatalysts for alkaline ORR/OER. WDC provided a favorable three-phase interface for heterogeneous reactions owing to its layered porous structure and genetic stability, thereby enabling mass diffusion and improving reaction kinetics. The CoFe2O4 spinel surface was reduced to bimetallic CoFe alloy to form abundant heterostructure interfaces that promote electron transfer. Under alkaline conditions, the optimized composite electrode exhibited a remarkable high half-wave potential of 0.85 V and an exceptionally low overpotential of 1.49 V. It also exhibited stable performance over an impressive 2340 cycles in a ZAB. Theoretical calculations also confirmed that the heterointerface addresses the issue of proton scarcity throughout the reaction and actively facilitates the creation of O–O bonds during the reversible transformation of oxygen. This study introduces a new concept for developing bifunctional and efficient electrocatalysts based on charcoal and encourages the sustainable and high-value use of forest biomass resources. Graphical Abstract

The bidirectional relationship between osteochondral defects (OCD) and osteoarthritis (OA), with each condition exacerbating the other, makes OCD regeneration in the presence of OA challenging. Type II collagen (Col2) is important in OCD regeneration and the management of OA, but its potential applications in cartilage tissue engineering are significantly limited. This study investigated the regeneration capacity of Col2 scaffolds in critical-sized OCDs under surgically induced OA conditions and explored the underlying mechanisms that promoted OCD regeneration. Furthermore, the repair potential of Col2 scaffolds was validated in over critical-sized OCD models. After 90 days or 150 days since scaffold implantation, complete healing was observed histologically in critical-sized OCD, evidenced by the excellent integration with surrounding native tissues. The newly formed tissue biochemically resembled adjacent natural tissue and exhibited comparable biomechanical properties. The regenerated OA tissue demonstrated lower expression of genes associated with cartilage degradation than native OA tissue but comparable expression of genes related to osteochondral anabolism compared with normal tissue. Additionally, transcriptome and proteome analysis revealed the hindrance of TGF-β-Smad1/5/8 in regenerated OA tissue. In conclusion, the engrafting of Col2 scaffolds led to the successful regeneration of critical-sized OCDs under surgically induced OA conditions by inhibiting the TGF-β-Smad1/5/8 signaling pathway.

Abstract Hyalectan cleavage may play an important role in extracellular matrix remodeling. However, the proteolytic enzyme responsible for hyalectan degradation for fetal membrane rupture at parturition remains unknown. Here, we reveal that versican (VCAN) is the major hyalectan in the amnion, where its cleavage increases at parturition with spontaneous rupture of membrane. We further reveal that ADAMTS4 is a crucial proteolytic enzyme for VCAN cleavage in the amnion. Inflammatory factors may enhance VCAN cleavage by inducing ADAMTS4 expression and inhibiting ADAMTS4 endocytosis in amnion fibroblasts. In turn, versikine, the VCAN cleavage product, induces inflammatory factors in amnion fibroblasts, thereby forming a feedforward loop between inflammation and VCAN degradation. Mouse studies show that intra-amniotic injection of ADAMTS4 induces preterm birth along with increased VCAN degradation and proinflammatory factors abundance in the fetal membranes. Conclusively, there is enhanced VCAN cleavage by ADAMTS4 in the amnion at parturition, which can be reenforced by inflammation.

Abstract The denoising of images is an important research direction in computer vision. We consider the image denoising task as an estimation problem of the filtering policy related to image features, which is different from end‐to‐end image mapping. Commonly used simple filters such as gaussian filtering and bilateral filtering have fixed global denoising policies. However, the denoising policies of different filters can only adapt to limited image features. To solve this problem, we propose a method that applies different filters to different spatial ranges and adjusts the parameters of these filters simultaneously. Since not all filters can be easily transformed into differentiable forms and it is difficult to obtain paired datasets of filter action areas, we use reinforcement learning (RL) methods to estimate the spatial domain action range and adjustable parameters of filters, respectively. Furthermore, for removing higher intensity noise, simple filters can iteratively approximate higher‐order denoising policies and obtain more accurate and stable denoising results with the increase of iteration steps. Experimental results show that our proposed method can not only generate intuitive and interpretable denoising policies but also achieve comparable or better visual effects and computational efficiency than baseline methods.

Abstract Although capacitive deionization (CDI) technology has been studied intensively for more than 20 years, its commercialization remains in the initial stage, which is partly caused by the insufficient knowledge exchange between academia and industry. This concept reviews multiple scaling‐up efforts in the CDI technology for treating real water streams, following a case‐by‐case fashion. While the cell architecture in pilot scales is limited to the membrane CDI, highlighting the necessary role of ion‐exchange components during scaling‐ups, different ways of electrode stacking, i. e., monopolar and bipolar, are available. The performance indicators of these CDI systems when treating real water streams are summarized to gain insights into industrial practices. Importantly, key discrepancies in cell components and performances between pilot‐scale and lab‐scale studies are emphasized. The main challenges in large‐scale CDI systems for industrial purposes are discussed, providing hints for a better integration of research and applications.

Abstract The shortage and unevenness of fossil energy sources are affecting the development and progress of human civilization. The technology of efficiently converting material resources into energy for utilization and storage is attracting the attention of researchers. Environmentally friendly biomass materials are a treasure to drive the development of new‐generation energy sources. Electrochemical theory is used to efficiently convert the chemical energy of chemical substances into electrical energy. In recent years, significant progress has been made in the development of green and economical electrocatalysts for oxygen reduction reaction (ORR). Although many reviews have been reported around the application of biomass‐derived catalytically active carbon (CAC) catalysts in ORR, these reviews have only selected a single/partial topic (including synthesis and preparation of catalysts from different sources, structural optimization, or performance enhancement methods based on CAC catalysts, and application of biomass‐derived CACs) for discussion. There is no review that systematically addresses the latest progress in the synthesis, performance enhancement, and applications related to biomass‐derived CAC‐based oxygen reduction electrocatalysts synchronously. This review fills the gap by providing a timely and comprehensive review and summary from the following sections: the exposition of the basic catalytic principles of ORR, the summary of the chemical composition and structural properties of various types of biomass, the analysis of traditional and the latest popular biomass‐derived CAC synthesis methods and optimization strategies, and the summary of the practical applications of biomass‐derived CAC‐based oxidative reduction electrocatalysts. This review provides a comprehensive summary of the latest advances to provide research directions and design ideas for the development of catalyst synthesis/optimization and contributes to the industrialization of biomass‐derived CAC electrocatalysis and electric energy storage.

Objectives: Secondary preventive care is important for monitoring the progression of cardiovascular disease (CVD). However, the factors that promote secondary prevention were not well understood. This study addressed this gap by investigating the impact of CVD diagnosis on preventive care utilization among midlife adults. Given the high prevalence of depression among this population, it further examined whether depression interacted with CVD diagnosis to affect preventive care utilization. Methods: The study sample included 6,222 midlife adults from six waves of the National Longitudinal Survey of Youth 1979 (NLSY79) collected between 2006 and 2016. Multiple logistic regressions were conducted to examine the relationship between a CVD diagnosis and each of the five types of preventive care utilization: influenza vaccinations, electrocardiography (EKG) and screening for high blood pressure, cholesterol, and blood sugar. Depression was then added to examine its possible moderation effect. Results: The results showed that midlife adults with a CVD diagnosis were more likely to utilize all five types of preventive care services. EKG, the most relevant preventive care type with CVD diagnosis, had the largest strength of likelihood. Depression strengthened the relationship between a CVD diagnosis and the utilization of blood pressure tests, but it showed no associations with other four types of preventive care utilization. Conclusions: The study findings indicate that a CVD diagnosis could serve as an opportunity for promoting secondary preventive care utilization. Future research needs to explore how a CVD diagnosis affects different population groups, and further explore the roles of depression.

Abstract Pancreatic ductal adenocarcinoma (PDAC) is a kind of tumor lacking nutrients due to its poor vascularity and desmoplasia. Recent studies have shown that cancer cells might achieve growth advantage through epitranscriptome reprogramming. However, the role of m5C in PDAC was not fully understood. We found that Aly/REF export factor (ALYREF), a reader of m5C modification, was overexpressed in PDAC, and associated with bad prognosis. In addition, the ALYREF expression was negatively related to CD8+ T cells infiltration in clinical samples. ALYREF knockdown decreased tumor growth in vivo partly dependent of immunity. ALYREF silencing decreased SLC7A5 expression and subsequently inactivated mTORC1 pathway, resulting in decreased tumor proliferation. Mechanically, ALYREF specifically recognized m5C sites in JunD mRNA, maintained the stabilization of JunD mRNA and subsequently upregulated transcription of SLC7A5. Since SLC7A5 was a key transporter of large neutral amino acids (LNAAs), overexpression of SLC7A5 on tumor cells depleted amino acid in microenvironment and restricted CD8+ T cells function. Moreover, ALYREF-JunD-SLC7A5 axis was overexpressed and negatively related with survival through TMA assays. In conclusion, this research revealed the relationship between m5C modification, amino acid transportation and immune microenvironment. ALYREF might be a novel target for PDAC metabolic vulnerability and immune surveillance.

Polytropic working conditions are prioritized by most intelligent adaptive methods. But the privacy and the inaccessibility of the source data during the transfer learning process are not considered. Moreover, the attention weights for each time point and neural network channel in the fault signals are also not addressed. Intending to deal with the problems above, we put forward a mixed attention network for source-free domain adaptation in bearing fault diagnosis work. We fully utilize the only-once source fault information to generate a source model with strong anomaly detection capabilities by our mixed attention network. Mixed attention network achieved an average accuracy of over 93% in both two datasets and achieved the highest accuracy in all tasks of the ablation experiment.

The increasing penetration of renewable energy resources with highly fluctuating outputs has placed increasing concern on the accuracy and timeliness of electric power system state estimation (SE). Meanwhile, we note that only a fraction of system states fluctuate at the millisecond level and require to be updated. As such, refreshing only those states with significant variation would enhance the computational efficiency of SE and make fast-continuous update of states possible. However, this is difficult to achieve with conventional SE methods, which generally refresh states of the entire system every 4–5 s. In this context, we propose a local hybrid linear SE framework using stream processing, in which synchronized measurements received from phasor measurement units (PMUs), and trigger/timing-mode measurements received from remote terminal units (RTUs) are used to update the associated local states. Moreover, the measurement update process efficiency and timeliness are enhanced by proposing a trigger measurement-based fast dynamic partitioning algorithm for determining the areas of the system with states requiring recalculation. In particular, non-iterative hybrid linear formulations with both RTUs and PMUs are employed to solve the local SE problem. The timeliness, accuracy, and computational efficiency of the proposed method are demonstrated by extensive simulations based on IEEE 118-, 300-, and 2383- bus systems.

Abstract Feedstock properties play a crucial role in thermal conversion processes, where understanding the influence of these properties on treatment performance is essential for optimizing both feedstock selection and the overall process. In this study, a series of van Krevelen diagrams were generated to illustrate the impact of H/C and O/C ratios of feedstock on the products obtained from six commonly used thermal conversion techniques: torrefaction, hydrothermal carbonization, hydrothermal liquefaction, hydrothermal gasification, pyrolysis, and gasification. Machine learning methods were employed, utilizing data, methods, and results from corresponding studies in this field. Furthermore, the reliability of the constructed van Krevelen diagrams was analyzed to assess their dependability. The van Krevelen diagrams developed in this work systematically provide visual representations of the relationships between feedstock and products in thermal conversion processes, thereby aiding in optimizing the selection of feedstock and the choice of thermal conversion technique.

Background And Objectives: Chronic active Epstein-Barr virus infection (CAEBV) is a lymphoproliferative disorder characterized by the increased numbers of EBV-infected T/natural killer (NK) cells and ongoing symptoms resembling infectious mononucleosis. Nonetheless, the exact correlation between peripheral lymphocyte subsets and the development of CAEBV remains uncertain. Methods: Consequently, we examined the levels of programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1) expression, the status of EBV infection, and the frequencies of peripheral lymphocyte subpopulations in 24 patients with CAEBV and 15 EBV-seronegative donors using flow cytometry. Results: Patients with CAEBV showed a notable rise in the expression levels of PD-1 and PD-L1 in peripheral T and NK cells compared to healthy donors (P < 0.05). The induction of PD-L1 expression was attributed to EBV infection. Moreover, most of the T cells infected with EBV displayed a memory phenotype characterized by the presence of CD45RO+. Additionally, patients with CAEBV showed markedly decreased frequency of helper T cells 1 (Th1) and naïve T (Tn) cells, and significantly elevated frequency of Th2 and effector-memory T (Tem) cells. Conclusions: To summarize, EBV might evade the immune system by inducing PD-1/PD-L1 expression in peripheral T and NK cells, and promoting Th2 immune response dominance. Additionally, it may establish long-term persistence by infecting memory T cells in CAEBV.

Abstract Expanding the application scenarios of wood-derived biochar guided by the conversion of traditional energy to new energy shows great promise as a field. As thrilling energy conversion apparatus, zinc-air batteries (ZABs) require cathode catalysts with high oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) activities and stability. Herein, two-dimensional nickel-iron hydroxide nanosheets were creatively assembled in N-doped wood-derived biochar (NiFe-LDH@NC) by an in-situ growth method. The categorized porous organization in wood-derived biochar facilitates the rapid seepage of electrolytes and rapid diffusion of reaction gases. The unique interfacial structure of biochar and NiFe-LDH accelerates electron transfer during oxygen electrocatalysis, and endows NiFe-LDH@NC with first-class catalytic activity and durability for ORR and OER. The ZAB derived from NiFe-LDH@NC showed elevated discharge productivity and cycle endurance, making it promising for viable applications. This work provided a convenient way for the conversion of wood-derived biochar to high-value added electrocatalysts. Graphical Abstract

Abstract The structural reconstruction mechanism of lignin and cellulose-derived biochars during direct graphitization under ultra-high temperatures was intensively investigated. It was demonstrated that cellulose-derived char was almost composed of carbon microcrystallites, whereas lignin-derived char reserved some of its skeleton structures, and such structural difference played a vital role in the morphology of formed graphitic layers. The results illustrated that the graphitized lignin-derived sample under 2800 ℃ had graphitic degree of 89.53%, interlayer spacing of 0.3363 nm and electronic conductivity of 104.6 S cm−1, while cellulose-derived sample had graphitic degree of 76.74%, layer distance of 0.3374 nm, and electronic conductivity of only 48.8 S cm−1. Combined with the results of structural analysis of the chars derived from lignin and cellulose, it was inferred that the stable and aromatic ring containing skeleton structure in lignin was beneficial to the ring-enlarging reconstruction and the formation of large areas of continuous graphitic layers during graphitizing process, leading to high electronic conductivity. Meanwhile, the interwoven microcrystallites in cellulose-derived char strongly restricted the expanding of continuous lamellar graphitic areas even at such ultra-high temperature, causing the formation of turbostratic structure with numerous structural defects as well, and finally resulting in relatively lower electronic conductivity. This work is expected to provide theoretical guidance for preparing high-performance functional carbon materials from lignocellulosic biomass. Graphical Abstract

Abstract The neutron capture cross section of $$ ^{181} $$ 181 Ta is relevant to s-process of nuclear astrophysics, extraterrestrial samples analysis in planetary geology and new generation nuclear energy system design. The $$^{181}$$ 181 Ta( $$n,\gamma $$ n , γ ) cross section had been measured between 1 eV and 800 keV at the back-streaming white neutron facility (Back-n) of China spallation neutron source(CSNS) using the time-of-flight (TOF) technique and $$\hbox {C}_{6}\,\hbox {D}_{6}$$ C 6 D 6 liquid scintillator detectors. The experimental results are compared with the data of several evaluated libraries and previous experiments in the resolved and unresolved resonance region. Resonance parameters are extracted using the R-Matrix code SAMMY in the 1–700 eV region. The astrophysical Maxwell average cross section(MACS) from kT = 5 to 100 keV is calculated over a sufficiently wide range of neutron energies. For the characteristic thermal energy of an astrophysical site, at kT = 30keV the MACS value of $$^{181}$$ 181 Ta is 834 ± 75 mb, which shows an obvious discrepancy with the Karlsruhe Astrophysical Database of Nucleosynthesis in Stars (KADoNiS) recommended value 766 ± 15 mb. The new measurements strongly constrain the MACS of $$^{181}$$ 181 Ta( $$n,\gamma $$ n , γ ) reaction in the stellar s-process temperatures.

Abstract Biochar with a highly accessible specific surface area can display a higher performance when it is used as the cathode of lithium-ion capacitors. Facing the complex composition and diversity of biomass precursors, there is a lack of a universally applicable method to construct hierarchical porous biochar controllably. In this work, a multi-stage activation strategy combining the feature of different activation methods is proposed for this target. To confirm the porous characteristic in prepared samples, N2 adsorption–desorption and transmission electron microscope were used. As the optimal sample, BC-P3K4S had the highest specific surface area of 3583.3 m2 g−1. Evaluated as the electrode for a lithium-ion capacitor, BC-P3K4S displayed a capacity of 139.1 mAh g−1 at 0.1 A g−1. After coupling it with pre-lithiated hard carbon, the full device exhibited a high energy density of 129.3 W h kg−1 at 153 W kg−1. The work outlined herein offers some insights into the preparation of hierarchical porous biochar from complex biomass by multistep activation method. Graphical Abstract

Abstract Knowledge gaps that limit the development of therapies for polycystic ovary syndrome (PCOS) concern various environmental factors that impact clinical characteristics. Circadian dysrhythmia contributes to glycometabolic and reproductive hallmarks of PCOS. Here, we illustrated the amelioration of Limosilactobacillus reuteri (L. reuteri) on biorhythm disorder-ignited dyslipidemia of PCOS via a microbiota-metabolite-liver axis. A rat model of long-term (8 weeks) darkness treatment was used to mimic circadian dysrhythmia-induced PCOS. Hepatic transcriptomics certified by in vitro experiments demonstrated that increased hepatic galanin receptor 1 (GALR1) due to darkness exposure functioned as a critical upstream factor in the phosphoinositide 3-kinase (PI3K)/protein kinase B pathway to suppress nuclear receptors subfamily 1, group D, member 1 (NR1D1) and promoted sterol regulatory element binding protein 1 (SREBP1), inducing lipid accumulation in the liver. Further investigations figured out a restructured microbiome-metabolome network following L. reuteri administration to protect darkness rats against dyslipidemia. Notably, L. reuteri intervention resulted in the decrease of Clostridium sensu stricto 1 and Ruminococcaceae UCG-010 as well as gut microbiota-derived metabolite capric acid, which could further inhibit GALR1-NR1D1-SREBP1 pathway in the liver. In addition, GALR antagonist M40 reproduced similar ameliorative effects as L. reuteri to protect against dyslipidemia. While exogenous treatment of capric acid restrained the protective effects of L. reuteri in circadian disruption-induced PCOS through inhibiting GALR1-dependent hepatic lipid metabolism. These findings purport that L. reuteri could serve for circadian disruption-associated dyslipidemia. Manipulation of L. reuteri–capric acid–GALR1 axis paves way for clinical therapeutic strategies to prevent biorhythm disorder-ignited dyslipidemia in PCOS women.

Abstract Background Inflammation of the fetal membranes is an indispensable event of labor onset at both term and preterm birth. Interleukin-33 (IL-33) is known to participate in inflammation via ST2 (suppression of tumorigenicity 2) receptor as an inflammatory cytokine. However, it remains unknown whether IL-33/ST2 axis exists in human fetal membranes to promote inflammatory reactions in parturition. Methods The presence of IL-33 and ST2 and their changes at parturition were examined with transcriptomic sequencing, quantitative real-time polymerase chain reaction, Western blotting or immunohistochemistry in human amnion obtained from term and preterm birth with or without labor. Cultured primary human amnion fibroblasts were utilized to investigate the regulation and the role of IL-33/ST2 axis in the inflammation reactions. A mouse model was used to further study the role of IL-33 in parturition. Results Although IL-33 and ST2 expression were detected in both epithelial and fibroblast cells of human amnion, they are more abundant in amnion fibroblasts. Their abundance increased significantly in the amnion at both term and preterm birth with labor. Lipopolysaccharide, serum amyloid A1 and IL-1β, the inflammatory mediators pertinent to labor onset, could all induce IL-33 expression through NF-κB activation in human amnion fibroblasts. In turn, via ST2 receptor, IL-33 induced the production of IL-1β, IL-6 and PGE2 in human amnion fibroblasts via the MAPKs-NF-κB pathway. Moreover, IL-33 administration induced preterm birth in mice. Conclusion IL-33/ST2 axis is present in human amnion fibroblasts, which is activated in both term and preterm labor. Activation of this axis leads to increased production of inflammatory factors pertinent to parturition, and results in preterm birth. Targeting the IL-33/ST2 axis may have potential value in the treatment of preterm birth.

The neutron capture measurement of natural rhenium was performed with the time-of-flight technique at the Back-n facility of the China Spallation Neutron Source in the energy range from 1 to 500 eV of the resolved resonance region (RRR) and from 5 to 400 keV in the unresolved resonance region (URR). Prompt γ-rays originating from neutron-induced capture events were detected by four C_{6}D_{6} detectors. The pulse height weighting technique and the double-bunch unfolding method based on the Bayesian theory were used in the data analysis. To obtain reliable measurement results, background subtraction, normalization, and corrections were carefully considered. The multilevel R-matrix Bayesian code SAMMY was used to extract the resonance parameters in the RRR. An absence of resonance near 392 eV is observed in our measurement, which has been observed in previous works. The average cross sections in the URR of natural rhenium relative to ^{197}Au were obtained in logarithmical equidistant energy bins with 20 bins per energy decade. The talys code was used to describe the average cross sections in the URR; the Maxwellian-averaged cross sections (MACSs) of ^{185}Re and ^{187}Re are given from kT=5 to 100 keV. At a thermal energy of kT=30 keV, the MACS value for ^{185}Re (1469±127 mb) is in good agreement with the Karlsruhe Astrophysical Database of Nucleosynthesis in Stars (KADoNIS) recommended value (1535±62 mb) within the error bars. By contrast, the value of 1361±118 mb for ^{187}Re shows a discrepancy with the KADoNiS recommended value (1160±57 mb).

Abstract Lung adenocarcinoma is still cancer with the highest mortality. Hypoxia and immunity play an essential role in the occurrence and development of tumors. Therefore, this study is mainly to find new early diagnosis and prognosis markers and explore the relationship among the markers and immunity and hypoxia, to improve the prognosis of patients. Firstly, based on the clinical database in TCGA, we determined the most critical clinicopathological parameters affecting the prognosis of patients through a variety of analysis methods. According to pathological parameters, logistic most minor absolute contraction selection operator (lasso), univariate and multivariate regression analysis, the risk genes related to early prognosis were screened, and the risk model was established. Then, in different risk groups, GSEA and CIBERSORT algorithms were used to analyze the distribution and enrichment of the immune cells and hypoxia, to study the effects of early prognostic indicators on hypoxia and immunity. At the same time, we analyzed the different levels of risk genes in normal cells (BSEA-2B) and tumor cells (H1299, A549, PC9, and H1975). Finally, A549 and PC9 cells were induced by CoCl2 to establish a hypoxic environment, and the correlation between risk genes and HIF1A was analyzed. The risk model based on risk genes (CYP4B1, KRT6A, and FAM83A) was accurate and stable for the prognosis of patients. It is closely related to immunity and hypoxia. In BSEA-2B cells, the mRNA and protein expression of CYP4B1 was higher, while the expression of KRT6A and FAM83A was lower. Finally, we found that FAM83A and HIF1A showed a significant positive correlation when A549 and PC9 cells were exposed to hypoxia. The discovery of early diagnostic markers related to immunity, hypoxia, and prognosis, provides a new idea for early screening and prognostic treatment of lung adenocarcinoma.

The low yield strength of the equiatomic CoCrFeMnNi high-entropy alloy (HEA) at ambient temperature severely limits its future application as engineering materials. Here, a CoCrFeMnNi HEA with a fully recrystallized structure and an excellent strength-ductility combination was prepared by post-deformation annealing (PDA) process (i.e., 773–1173 K for 2 h) after selective laser melting. The evolution of the microstructures and mechanical properties of the as-printed and PDA-processed samples were systemically studied, while the strengthening mechanism of PDA-processed samples was clarified. The high density of dislocations and anisotropic columnar grains in the as-printed samples improved the rate of stored deformation energy, thus effectively promoting grain refinement during the PDA process. Compared to the average grain size of 21.26 μm of the as-printed sample, the average grain size of the PDA-873 sample was decreased to 1.20 μm after full recrystallization. Especially in the PDA-873 sample, we found a large amount of high angle grain boundaries (HAGBs) (∼98.3%) and twin boundaries (TBs) (∼46.6%). Besides, some Cr and Mn-rich oxide particles also precipitated in the PDA-processed samples. The main strengthening mechanisms of PDA-processed samples can be attributed to grain boundary strengthening. The PDA-873 sample exhibits a high yield strength, which is twice as large as that of the as-printed samples, without sacrificing ductility significantly. The present work provides an effective way to manipulate grain size and precipitates in HEAs.

Background: Efficacy of ruxolitinib cream, a topical Jak1/Jak2 inhibitor, was demonstrated in a phase 2 trial in patients with vitiligo. Objective: This study aimed to characterize circulating inflammatory biomarker profiles in patients who demonstrated ≥50% improvement in facial Vitiligo Area Scoring Index scores by week 24 (group 1) and those who did not (group 2). Design: This was a posthoc analysis of a multicenter, randomized, double-blind, vehicle-controlled, phase 2 study in which screening was conducted between June 7, 2017 and March 21, 2018. Population: Patients aged between 18 and 75 years with vitiligo, including depigmentation affecting ≥0.5% of body surface area on the face and ≥3% of body surface area on nonfacial areas, were eligible. Intervention: Patients applied 1.5% ruxolitinib cream to lesions once or twice daily for 52 weeks. Main outcomes and measures: Patients were grouped by achievement of ≥50% improvement in facial Vitiligo Area Scoring Index at week 24. Proteomic analysis was performed on baseline serum samples. Results: Mean ± standard error facial Vitiligo Area Scoring Index in group 1 (n = 30) versus group 2 (n = 27) improved by 79.9 ± 4.0% versus 1.1 ± 7.3% and 91.9 ± 1.5% versus 25.1 ± 13.4% at weeks 24 and 52, respectively. Broad proteomic analysis revealed 76 proteins (of 1,104 tested) that were differentially expressed between groups 1 and 2 at baseline (P < 0.05). Ten distinct proteins were upregulated in group 1; 64 were elevated in group 2. Conclusion: This analysis identified potential differences between patients who achieved ≥50% improvement in facial Vitiligo Area Scoring Index at 24 weeks and those who did not that require deeper scientific interrogation and may be important in stratifying therapeutic benefit for patients with vitiligo. Trial Registration: The original study was registered at ClinicalTrials.gov, NCT03099304.

IntroductionThis study aimed to investigate the daily sound exposure of hearing aid (HA) users during the COVID-19 pandemic, with a specific focus on the impact of different governance intervention levels.MethodsModern HA technology was employed to measure and compare the sound exposure of HA users in three distinct periods: pre-pandemic, and two 14-day periods during the pandemic, corresponding to varying levels of governance interventions. The study sample comprised a total of 386 HA users in Europe during the pandemic, with daily sound exposure data collected as part of the main dataset.ResultsThe results revealed that, during the pandemic, the equivalent continuous sound pressure level (SPL) experienced by HA users decreased, while the signal-to-noise ratio (SNR) increased compared to the pre-pandemic period. Notably, this impact was found to be more pronounced (p

Little is known about whether doctors’ recommendations encourage healthy behaviors among individuals with hypertension in Brazil. This study examined the biological, social, and health factors related to doctor’s recommendations and the associations between doctor’s recommendations and healthy behaviors. The sample consisted of individuals with hypertension (N = 18,260) from Brazil’s 2019 National Health Survey. The outcomes examined included smoking, drinking, diet, salt intake, physical activity, and doctor visits. Study findings indicated that more than 80% of people with hypertension in Brazil received doctors’ recommendations to adhere to medical care and engage in healthy behaviors. Those who received recommendations were more likely to practice healthy eating and exercise regularly but also to be obese/overweight, smoke, and drink excessively. Nonetheless, the findings concerning diet and exercise suggest the value of doctors’ recommendations for individuals with hypertension in Brazil.

In photography, accurate exposure is the key to taking high-quality photos, particularly images with uneven exposure levels. Global exposure operations are usually difficult to effectively strengthen the various regions of the image. To achieve a balanced exposure level in different regions of the image, we propose a novel algorithm inspired by the luminance masking frequently employed by professional photographers. We use reinforcement learning to adaptively generate guiding regions and adjusting parameters as a basis for multi-step exposure fusion, to enhance the overall quality of the image. Firstly, reinforcement learning is employed to automatically segment the single image to be enhanced into multiple sub-images, with corresponding appropriate adjusting parameters for each sub-image generated. Then, the input image is enhanced using the local adjusting parameters, yielding a set of images with varying enhancing degrees. Finally, these images are fused in an exposure process to obtain the final result. Experimental results show that our method not only generates intuitive and interpretable guiding regions, but also its performance is comparable to that of other contemporaneous methods.

China's fishing moratorium policy has been implemented since 1995, and its scope, time and type of moratorium have been continuously expanded and improved. The implementation and implementation of this policy have made great contributions to the sustainable development of China's fishery resources. Fishermen, as the core carrier of the implementation of the moratorium policy, their satisfaction with the moratorium policy is the key component of the implementation of the moratorium policy. Based on the survey of 541 fishermen in Dalian, Liaoning Province, the logistic model was applied to study fishermen’ satisfaction of the fishing moratorium policy, and the results showed that: (1) Fishermen's overall satisfaction with the fishing moratorium policy was relatively high, with 77.4% of fishermen holding a satisfactory attitude. (2) Fishermen with poor health condition were less satisfied with the fishing moratorium policy. (3) Fishermen with a high proportion of fishery income were less satisfied with the fishing moratorium policy. (4) Satisfaction with the work of government departments was significantly and positively correlated with satisfaction with the fishing moratorium policy. Based on the above findings, this paper put forward corresponding policy recommendations for the fishing moratorium system.

Based on mixed lubrication analysis, considering the influence of rough interface contact stiffness, contact damping, and interface friction on the gear transmission system, the relationship between interface contact and the overall performance of the gear transmission system has been established. First, the surface topography is characterized using statistical parameters of rough surfaces, and the contact stiffness and damping for tooth surfaces with different roughnesses are calculated. Subsequently, a six degree of freedom gear tribo-dynamics coupling model is developed. Finally, the established tribo-dynamics model is employed to investigate the relationship between surface roughness and the overall performance of the gear transmission system. This study provides a more intimate connection between the contact interface and the general behavior of the gear transmission system, enabling a better representation of real-world engineering problems. The research findings reveal that contact stiffness and damping decrease with increasing surface roughness. Higher roughness leads to greater gear vibration amplitude. Moreover, elevated surface roughness results in intensified meshing force and more significant energy loss. Surprisingly, when the roughness is appropriate, gears with rough surfaces lose less energy than those with smooth surfaces.

A low-cost efficient electrocatalyst for both oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) is urgently required for the commercialization of Zn-air batteries. Herein, CoMn nanoalloys encapsulated in nitrogen-doped hollow carbon architectures (CoMn@NHC) as dual electrocatalysts for Zn-air batteries were developed successfully. The obtained CoMn@NHC nanohybrid expresses excellent electrocatalytic performances for ORR (E1/2 = 0.87 V) and OER (Ei=10 = 1.51 V). More encouragingly, a homemade aqueous Zn-air battery using CoMn@NHC catalyst delivers a larger peak power density of 92.3 mW cm−2 and excellent stability of nearly 300 h, outperforming the commercial Pt/C + RuO2. The remarkable electrocatalytic performances are owing to the unique microstructure and the synergistic effect between CoMn alloy and N-doped carbon substrate. This study opens a new way for designing high-efficient bifunctional electrocatalysts for application in renewable energy facilities.

Abstract Canine hip dysplasia (HD) is a multifactorial disease caused by interactions between genetic and environmental factors. HD, which mainly occurs in medium- to large-sized dogs, is a disease that causes severe pain and requires surgical intervention. However, the procedure is not straight-forward, and the only way to ameliorate the situation is to exclude individual dogs with HD from breeding programs. Recently, prime editing (PE), a novel genome editing tool based on the CRISPR-Cas9 system, has been developed and validated in plants and mice. In this study, we successfully corrected a mutation related to HD in Labrador retriever dogs for the first time. We collected cells from a dog diagnosed with HD, corrected the mutation using PE, and generated mutation-corrected dogs by somatic cell nuclear transfer. The results indicate that PE technology can potentially be used as a platform to correct genetic defects in dogs.

Abstract Compared with the traditional heteroatom doping, employing heterostructure is a new modulating approach for carbon‐based electrocatalysts. Herein, a facile ball milling‐assisted route is proposed to synthesize porous carbon materials composed of abundant graphene/hexagonal boron nitride (G/h‐BN) heterostructures. Metal Ni powder and nanoscale h‐BN sheets are used as a catalytic substrate/hard template and “nucleation seed” for the formation of the heterostructure, respectively. As‐prepared G/h‐BN heterostructures exhibit enhanced electrocatalytic activity toward H2O2 generation with 86%–95% selectivity at the range of 0.45–0.75 V versus reversible hydrogen electrode (RHE) and a positive onset potential of 0.79 versus RHE (defined at a ring current density of 0.3 mA cm−2) in the alkaline solution. In a flow cell, G/h‐BN heterostructured electrocatalyst has a H2O2 production rate of up to 762 mmol gcatalyst−1 h−1 and Faradaic efficiency of over 75% during 12 h testing, superior to the reported carbon‐based electrocatalysts. The density functional theory simulation suggests that the B atoms at the interface of the G/h‐BN heterostructure are the key active sites. This research provides a new route to activate carbon catalysts toward highly active and selective O2‐to‐H2O2 conversion.

Abstract We describe new publicly available, multi‐year formaldehyde (HCHO) data records from the Ozone Mapping and Profiler Suite (OMPS) nadir mapper (NM) instruments on the Suomi NPP and NOAA‐20 satellites. The OMPS‐NM instruments measure backscattered UV light over the globe once per day, with spatial resolutions close to nadir of 50 × 50 km2 (OMPS/Suomi‐NPP) and 17 × 17 km2 or 12 × 17 km2 (OMPS/NOAA‐20). After a preliminary instrument line shape and wavelength calibration using on‐orbit observations, we use the backscatter measurements in a direct spectral fit of radiances, in combination with a nadir reference spectrum collected over a clean area, to determine slant columns of HCHO. The slant columns are converted to vertical columns using air mass factors (AMFs) derived through scene‐by‐scene radiative transfer calculations. Finally, a correction is applied to account for background HCHO in the reference spectrum, as well as any remaining high‐latitude biases. We investigate the consistency of the OMPS products from Suomi NPP and NOAA‐20 using long‐term monthly means over 12 geographic regions, and also compare the products with publicly available TROPOMI HCHO observations. OMPS/Suomi‐NPP and OMPS/NOAA‐20 monthly mean HCHO vertical columns are highly consistent (r = 0.98), with low proportional (2%) and offset (2 × 1014 molecules cm−2) biases. OMPS HCHO monthly means are also well‐correlated with those from TROPOMI (r = 0.92), although they are consistently 10% ± 16% larger in polluted regions (columns >8 × 1015 molecules cm−2). These differences result primarily from differences in AMFs.

Abstract For a “Carbon Neutrality” society, electrochemical energy storage and conversion (EESC) devices are urgently needed to facilitate the smooth utilization of renewable and sustainable energy where the electrode materials and catalysts play a decisive role. However, the efficiency of the current trial‐and‐error research paradigm largely lags behind the imminent demands of EESC requiring increasingly improved performance. The emerged machine learning (ML), a subfield of artificial intelligence, is capable of evaluating and analyzing big data for hidden rules. In this regard, the relationships between the structure and performance of the key materials can be more efficiently revealed, which fundamentally revolutionizes the material research manner of the current EESC devices. In this review, the typical ML algorithms utilized in EESC development are first introduced. Then, focused attention has been paid to multiple aspects of applying ML to reshape the materials research for EESC. In addition to highlighting the emerging prospect, the challenges which are still hindering the further development of this emerging field are also discussed.

Intermittent fasting (IF) could not work well in females indicating that additional interventions might be necessary to improve outcomes. We here investigated whether Pu-erh tea extract (PTE) intake could enhance anti-obesity effect of IF in female mice and explored the underlying mechanisms. The combination of PTE and IF treated obesity by reducing lipogenesis and enhancing adipose thermogenesis. This combination might decrease follicle-stimulating hormone (FSH) to reduce FSH-mediated UCP1 inhibition by AMPK/PGC1α/UCP1 pathways, finally promoting adipose thermogenesis. Based on this, we speculated increase of FSH might be a key reason for poor anti-obesity effect in female mice under IF. Besides, this combination modulated the composition of gut microbes (restored Firmicutes/Bacteroidetes and improved Akkermansia abundance) by protecting the intestinal barrier, and further promoted the production of SCFAs especially butyrate which might finally induce thermogenesis in adipose. Our results suggested this combination could be an effective strategy to combating obesity for females.

Abstract Superplastic metals that exhibit exceptional ductility (>300%) are appealing for use in high‐quality engineering components with complex shapes. However, the wide application of most superplastic alloys has been constrained due to their poor strength, the relatively long superplastic deformation period, and the complex and high‐cost grain refinement processes. Here these issues are addressed by the coarse‐grained superplasticity of high‐strength lightweight medium entropy alloy (Ti43.3V28Zr14Nb14Mo0.7, at.%) with a microstructure of ultrafine particles embedded in the body‐centered‐cubic matrix. The results demonstrate that the alloy reached a high coarse‐grained superplasticity greater than ≈440% at a high strain rate of 10−2 s−1 at 1173 K and with a gigapascal residual strength. A consecutively triggered deformation mechanism that sequences of dislocation slip, dynamic recrystallization, and grain boundary sliding in such alloy differs from conventional grain‐boundary sliding in fine‐grained materials. The present results open a pathway for highly efficient superplastic forming, broaden superplastic materials to the high‐strength field, and guide the development of new alloys.

232Th/233U fuel cycle is an alternate candidate for future nuclear energy. Neutron-induced fission cross section of 232Th is one of the important nuclear data if using thorium as the fuel in the future. 232Th(n, f) cross sections from 1 to 300 MeV were measured at China Spallation Neutron Source (CSNS) Back-streaming neutron facility (Back-n) relative to 235U(n, f) and n-p scattering. A fast ionization chamber for fission cross section measurement (FIXM) and a proton recoil telescope (PRT) were used to perform the measurement. The neutron energy in this measurement reaches up to 300 MeV which is supposed to be the highest among the current Experimental Nuclear Reaction Data (EXFOR) library. It stands as the only experimental data in the region of 200-300 MeV in EXFOR as well. The experimental and evaluated data of 232Th(n, f) cross section above 60 MeV are scarce, the measurement data of this work will be valuable references for future evaluation in high energy. For the data below 60 MeV, most of our data are more consistent with ENDF/B-VIII.0, excepting in the region of 1-2 MeV where our data are more in favor of CENDL-3.2.

Background: The prognosis of lung adenocarcinoma (LUAD) is poor. Infection with coronavirus disease 2019 (COVID-19) may further worsen the outcome of LUAD. This study utilized the immune model and the COVID-19 receptor signal to identify the potential immune structure affecting the prognosis of COVID-19 and LUAD. Methods: A prognostic model was established and verified. The correlation between immune cells and risk score was examined through a variety of immune calculation methods. Gene set variation analysis (GSVA) was used to explore the correlation between the immune signaling pathway, risk model, COVID-19 binding receptor (CO19ORS) signal, and different clinicopathological factors. Results: The analysis showed that the prognosis of patients was better in the low-risk group versus the high-risk group. The tertiary lymphoid structure dominated by T and B cells (TLS1) can improve the prognosis of patients in the low-risk group. Interestingly, the CO19ORS was enriched only in females and aged >65 years. The age group >65 years is closely related to the tertiary lymphatic structure of the newborn (TLS2), while the female sex is closely related to the TLS2 and TLS1 signature. The two groups exhibited a high level of inflammation-related signal distribution. In the near future, I will collect LUAD and COVID-19 related organizations to verify the changes of 8 risk protein. Conclusion: TLS1 structure may improve the prognosis of patients with LUAD and SARS-COV-2 (Severe acute respiratory syndrome coronavirus 2). This unexpected discovery provides new insight into the comprehensive treatment of patients with LUAD and SARS-COV-2.

AIM: To explore the clinical efficacy of the myopic with moderate to high astigmatism correction between corneal topography-guided femtosecond laser in situ keratomileusis(FS-LAISK)and Toric implantable collamer lens(TICL).METHODS: A total of 60 patients(115 eyes)with moderate to high astigmatism in myopia(115 eyes)from June 2019 to June 2021 and treated in the refractive center of Heyuan Aier Eye Hospital were enrolled in the study, then were divided into Group A and Group B according to the operations they would accept. There were 32 patients(62 eyes)in the Group A treated with corneal topography-guided FS-LASIK and 28 patients(53 eyes)in the Group B treated with TICL implantation. Uncorrected visual acuity(UCVA), best corrected visual acuity(BCVA), spherical diopter and residual astigmatism were recorded preoperatively and postoperatively at 3mo, surgical safety and efficacy were evaluated, and the Alpins vector analysis was used to evaluate the astigmatism.RESULTS: The postoperative at 3mo, there were no differences in the safety index(1.163±0.167 vs 1.136±0.194)and the efficacy index(1.145±0.159 vs 1.123±0.196)between the patients of the two groups(P>0.05). However, the astigmatism vector analysis showed that there were statistically differences in the index of success index [0.125(0.091, 0.200)vs 0.200(0.167, 0.250)], the correction index [1.000(0.902, 1.066)vs 0.834(0.783, 0.869)] and the flattening index [1.000(0.922, 1.079)vs 0.835(0.795, 0.870)](P

Abstract Background Enhancer of zeste homolog 2 (EZH2)-mediated histone 3 lysine 27 trimethylation (H3K27me3) is a transcription silencing mark, which is indispensable for cell lineage specification at the early blastocyst stage. This epigenetic repression is maintained in placental cytotrophoblasts but is lifted when cytotrophoblasts differentiate into syncytiotrophoblasts. However, the physiological impact of this lift remains elusive. Here, we investigated whether lifting EZH2-mediated H3K27me3 during syncytialization upregulates the expression of a short secretory isoform of a disintegrin and metalloprotease 12 (ADAM12-S), a well-recognized placenta-derived protease that cleaves insulin-like growth factor binding protein 3 to increase insulin-like growth factor (IGF) bioavailability for the stimulation of fetoplacental growth. The transcription factor and the upstream signal involved were also explored. Methods Human placenta tissue and cultured primary human placental cytotrophoblasts were utilized to investigate the role of EZH2-mediated H3K27me3 in ADAM12-S expression and the associated transcription factor and upstream signal during syncytialization. A mouse model was used to examine whether inhibition of EZH2-mediated H3K27me3 regulates placental ADAM12-S expression and fetoplacental growth. Results EZH2 and ADAM12 are distributed primarily in villous cytotrophoblasts and syncytiotrophoblasts, respectively. Increased ADAM12-S expression, decreased EZH2 expression, and decreased EZH2/H3K27me3 enrichment at the ADAM12 promoter were observed during syncytialization. Knock-down of EZH2 further increased ADAM12-S expression in trophoblasts. Syncytialization was also accompanied by increased STAT5B expression and phosphorylation as well as its enrichment at the ADAM12 promoter. Knock-down of STAT5B attenuated ADAM12-S expression during syncytialization. Epidermal growth factor (EGF) was capable of inducing ADAM12-S expression via stimulation of STAT5B expression and phosphorylation during syncytialization. Mouse studies revealed that administration of an EZH2 inhibitor significantly increased ADAM12-S levels in maternal blood and fetoplacental weights along with decreased H3K27me3 abundance and increased ADAM12-S expression in the placenta. Conclusions Lifting EZH2-mediated H3K27me3 increases ADAM12-S expression during syncytialization with the participation of EGF-activated STAT5B, which may lead to elevation of ADAM12-S level in maternal blood resulting in increased IGF bioavailability for the stimulation of fetoplacental growth in pregnancy. Our studies suggest that the role of EZH2-mediated H3K27me3 may switch from cell lineage specification at the early blastocyst stage to regulation of fetoplacental growth in later gestation.

Abstract Integrated electrochemical sensing platforms in wearable devices have great prospects in biomedical applications. However, traditional electrochemical platforms are generally fabricated on airtight printed circuit boards, which lack sufficient flexibility, air permeability, and conformability. Liquid metals at room temperature with excellent mobility and electrical conductivity show high promise in flexible electronics. This paper presents a miniaturized liquid metal-based flexible electrochemical detection system on fabric, which is intrinsically flexible, air-permeable, and conformable to the body. Taking advantage of the excellent fluidity and electrical connectivity of liquid metal, a double-layer circuit is fabricated that significantly miniaturizes the size of the whole system. The linear response, time stability, and repeatability of this system are verified by resistance, stability, image characterization, and potassium ferricyanide tests. Finally, glucose in sweat can be detected at the millimolar level using this sensing system, which demonstrates its great potential for wearable and portable detection in biomedical fields, such as health monitoring and point-of-care testing.

Abstract Background The human amnion is an intrauterine tissue which is involved in the initiation of parturition. In-depth understanding of gene expression signatures of individual cell types in the amnion with respect to membrane rupture at parturition may help identify crucial initiators of parturition for the development of specific strategies to prevent preterm birth, a leading cause of perinatal mortality. Results Six major cell types were revealed in human amnion including epithelial cells, fibroblasts and immunocytes as well as three other cell types expressing dual cell markers including epithelial/fibroblast, immune/epithelial and immune/fibroblast markers. The existence of cell types expressing these dual cell markers indicates the presence of epithelial-mesenchymal (EMT), epithelial-immune (EIT) and mesenchymal-immune (MIT) transitions in amnion at parturition. We found that the rupture zone of amnion exhibited some specific increases in subcluster proportions of immune and EMT cells related to extracellular matrix remodeling and inflammation in labor. The non-rupture zone exhibited some common changes in subcluster compositions of epithelial and fibroblast cells with the rupture zone in labor, particularly those related to oxidative stress and apoptosis in epithelial cells and zinc ion transport in fibroblasts. Moreover, we identified that C–C motif chemokine ligand 20 (CCL20) was among the top up-regulated genes in amnion epithelial cells, fibroblasts and immunocytes in the rupture zone at parturition. Studies in pregnant mice showed that administration of CCL20 induced immunocytes infiltration to tissues at the maternal–fetal interface and led to preterm birth. Conclusions Apart from the conventional epithelial, fibroblast and immunocytes, human amnion cells may undergo EMT, EIT and FIT in preparation for parturition. Intense inflammation and ECM remodeling are present in the rupture zone, while enhanced apoptosis and oxidative stress in epithelial cells and zinc ion transport in fibroblasts are present in amnion regardless of the rupture zones at parturition. CCL20 derived from the major cell types of the amnion participates in labor onset.

Abstract With excellent electrical conductivity, fluidity, rheological property, and biocompatibility, gallium has been intensively studied in the fields of flexible electronics and devices, thermal management, and soft robotics. However, the large degree of supercooling of gallium presents a large limitation for phase transition‐related applications such as the very low temperature required for solidification, the impurities, and side effects brought in by nucleating agents. In this study, solidification process of liquid gallium by using solid gallium as a nucleating agent is discovered to be fast and facile at room temperature compared with other agent materials including copper, iron, and nickel. Quantificationally, solidified gallium as a nucleating agent, can effectively reduce the supercooling degree from about 66.3 to 14.8 °C. The freezing velocity can reach to 200 mm3 min−1. The possible mechanism is reducing the energy barrier via adding nucleation site, allowing rapid solidification at room temperature accompanying heat dissipation. Moreover, micromechanical properties are compared between raw solid Ga and the solidified Ga induced by Ga agent, which suggests a slight decrease in mechanical strength at room temperature with the nucleating agent. It will be beneficial to understand the phase change and also provide guidance for the application of gallium regarding its mechanical properties.

Background: Prelabor rupture of the fetal membranes (PROM) is a major contributor to adverse perinatal outcomes. Some epidemiologic studies explored the association between maternal PM2.5 exposure and PROM but failed to treat the labor induction and prelabor cesarean section as censored observations. Objective: We aimed to evaluated whether acute and chronic maternal ambient PM2.5 exposure may increase the risk of PROM in China. Methods: This study was based on the China Labor and Delivery Survey, a nationwide multicenter investigation. Included in the current analysis were 45,879 singleton spontaneous births in 96 hospitals in mainland China from 2015 to 2017. Outcomes were PROM, preterm PROM (

Abstract Background Insulin resistance (IR) contributes to ovarian dysfunctions in polycystic ovarian syndrome (PCOS) patients. Serum amyloid A1 (SAA1) is an acute phase protein produced primarily by the liver in response to inflammation. In addition to its role in inflammation, SAA1 may participate in IR development in peripheral tissues. Yet, expressional regulation of SAA1 in the ovary and its role in the pathogenesis of ovarian IR in PCOS remain elusive. Methods Follicular fluid, granulosa cells and peripheral venous blood were collected from PCOS and non-PCOS patients with and without IR to measure SAA1 abundance for analysis of its correlation with IR status. The effects of SAA1 on its own expression and insulin signaling pathway were investigated in cultured primary granulosa cells. Results Ovarian granulosa cells were capable of producing SAA1, which could be induced by SAA1 per se. Moreover, the abundance of SAA1 significantly increased in granulosa cells and follicular fluid in PCOS patients with IR. SAA1 treatment significantly attenuated insulin-stimulated membrane translocation of glucose transporter 4 and glucose uptake in granulosa cells through induction of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) expression with subsequent inhibition of Akt phosphorylation. These effects of SAA1 could be blocked by inhibitors for toll-like receptors 2/4 (TLR 2/4) and nuclear factor kappa light chain enhancer of activated B (NF-κB). Conclusions Human granulosa cells are capable of feedforward production of SAA1, which significantly increased in PCOS patients with IR. Excessive SAA1 reduces insulin sensitivity in granulosa cells via induction of PTEN and subsequent inhibition of Akt phosphorylation upon activation of TLR2/4 and NF-κB pathway. These findings highlight that elevation of SAA1 in the ovary promotes the development of IR in granulosa cells of PCOS patients.

Abstract Machine learning (ML) has demonstrated promise in predicting mortality; however, understanding spatial variation in risk factor contributions to mortality rate requires explainability. We applied explainable artificial intelligence (XAI) on a stack-ensemble machine learning model framework to explore and visualize the spatial distribution of the contributions of known risk factors to lung and bronchus cancer (LBC) mortality rates in the conterminous United States. We used five base-learners—generalized linear model (GLM), random forest (RF), Gradient boosting machine (GBM), extreme Gradient boosting machine (XGBoost), and Deep Neural Network (DNN) for developing stack-ensemble models. Then we applied several model-agnostic approaches to interpret and visualize the stack ensemble model's output in global and local scales (at the county level). The stack ensemble generally performs better than all the base learners and three spatial regression models. A permutation-based feature importance technique ranked smoking prevalence as the most important predictor, followed by poverty and elevation. However, the impact of these risk factors on LBC mortality rates varies spatially. This is the first study to use ensemble machine learning with explainable algorithms to explore and visualize the spatial heterogeneity of the relationships between LBC mortality and risk factors in the contiguous USA.

The effective utilization of charcoal and tar byproducts is a challenge for pyrolysis gasification of bamboo. Herein, the bamboo tar was modified via polymerization and acted as a new adhesive for the preparation of excellent bamboo-charcoal-derived molding activated carbon (MBAC). As compared with pristine tar and other adhesives, the aromatization of tar with phenol increased its molecular weight, oxygenic functional groups, and thermal stability, leading to the decreased blocking impact of charcoal pore and improved bonding and pyrolytic crosslinking effect between charcoal particles. These further contribute to the high mechanical strength, specific surface area, pore volume, and amount of oxygenic functional groups for fabricated MBAC. Owing to the high microporous volume of MBAC, it exhibited 385 mg·g−1 toluene and 75.2% tetrachloride gas adsorption performances. Moreover, the pseudo-first-order, pseudo-second-order, and Bangham models were used to evaluate the kinetic data. The toluene adsorption process conforms to the Bangham kinetic model, suggesting that the diffusion mechanism of toluene adsorption mainly followed intraparticle diffusion.

Inflammation of the fetal membranes is an indispensable event of parturition, with increasing prostaglandin E2 (PGE2) synthesis as one of the ultimate products that prime labor onset. In addition to PGE2, the fetal membranes also boast a large capacity for cortisol regeneration. It is intriguing how increased PGE2 synthesis is achieved in the presence of increasing amounts of classical anti-inflammatory glucocorticoids in the fetal membranes at parturition. 15(S)-hydroxyeicosatetraenoic acid (15(S)-HETE) synthesized by lipoxygenase 15/15B (ALOX15/15B) has been shown to enhance inflammation-induced PGE2 synthesis in amnion fibroblasts. Here, we examined whether glucocorticoids could induce ALOX15/15B expression and 15(S)-HETE production to promote PGE2 synthesis in amnion fibroblasts at parturition. We found that cortisol and 15(S)-HETE abundance increased parallelly in the amnion at parturition. Cortisol induced ALOX15/15B expression and 15(S)-HETE production paradoxically in amnion fibroblasts. Mechanism study revealed that this paradoxical induction was mediated by p300-mediated histone acetylation and interaction of glucocorticoid receptor with transcription factors CREB and STAT3. Conclusively, cortisol regenerated in the fetal membranes can paradoxically induce ALOX15/15B expression and 15(S)-HETE production in human amnion fibroblasts, which may further assist in the induction of PGE2 synthesis in the inflammatory responses of the fetal membranes for parturition.

Human parturition is associated with massive arachidonic acid (AA) mobilization in the amnion, indicating that large amounts of AA-derived eicosanoids are required for parturition. Prostaglandin E2 (PGE2) synthesized from the cyclooxygenase (COX) pathway is the best characterized AA-derived eicosanoid in the amnion which plays a pivotal role in parturition. The existence of any other pivotal AA-derived eicosanoids involved in parturition remains elusive. Here, we screened such eicosanoids in human amnion tissue with AA-targeted metabolomics and studied their role and synthesis in parturition by using human amnion fibroblasts and a mouse model. We found that lipoxygenase (ALOX) pathway-derived 15(S)-hydroxyeicosatetraenoic acid (15(S)-HETE) and its synthetic enzymes ALOX15 and ALOX15B were significantly increased in human amnion at parturition. Although 15(S)-HETE is ineffective on its own, it potently potentiated the activation of NF-κB by inflammatory mediators including lipopolysaccharide, interleukin-1β, and serum amyloid A1, resulting in the amplification of COX-2 expression and PGE2 production in amnion fibroblasts. In turn, we determined that PGE2 induced ALOX15/15B expression and 15(S)-HETE production through its EP2 receptor-coupled PKA pathway, thereby forming a feed-forward loop between 15(S)-HETE and PGE2 production in the amnion at parturition. Our studies in pregnant mice showed that 15(S)-HETE injection induced preterm birth with increased COX-2 and PGE2 abundance in the fetal membranes and placenta. Conclusively, 15(S)-HETE is identified as another crucial parturition-pertinent AA-derived eicosanoid in the amnion, which may form a feed-forward loop with PGE2 in parturition. Interruption of this feed-forward loop may be of therapeutic value for the treatment of preterm birth.

BackgroundListening programs enable hearing aid (HA) users to change device settings for specific listening situations and thereby personalize their listening experience. However, investigations into real-world use of such listening programs to support clinical decisions and evaluate the success of HA treatment are lacking. ObjectiveWe aimed to investigate the provision of listening programs among a large group of in-market HA users and the context in which the programs are typically used. MethodsFirst, we analyzed how many and which programs were provided to 32,336 in-market HA users. Second, we explored 332,271 program selections from 1312 selected users to investigate the sound environments in which specific programs were used and whether such environments reflect the listening intent conveyed by the name of the used program. Our analysis was based on real-world longitudinal data logged by smartphone-connected HAs. ResultsIn our sample, 57.71% (18,663/32,336) of the HA users had programs for specific listening situations, which is a higher proportion than previously reported, most likely because of the inclusion criteria. On the basis of association rule mining, we identified a primary additional listening program, Speech in Noise, which is frequent among users and often provided when other additional programs are also provided. We also identified 2 secondary additional programs (Comfort and Music), which are frequent among users who get ≥3 programs and usually provided in combination with Speech in Noise. In addition, 2 programs (TV and Remote Mic) were related to the use of external accessories and not found to be associated with other programs. On average, users selected Speech in Noise, Comfort, and Music in louder, noisier, and less-modulated (all P

Serum amyloid A (SAA) is one of the acute phase proteins released primarily from the liver in response to infection, inflammation and trauma. Emerging evidence indicates that SAA may function as a host-derived damage-associated molecular pattern (DAMP) protein to sense danger signals in pregnancy. The plasma SAA levels in maternal circulation are significantly increased in normal parturition, particularly in postpartum, as well as in gestational disorders such as premature preterm rupture of membranes, pre-eclampsia, gestational diabetes, and recurrent spontaneous abortion. It is likely that SAA acts as a non-specific DAMP molecule in response to inflammation and trauma experienced under these conditions. Notably, SAA can also be synthesized locally in virtually all gestational tissues. Within these gestational tissues, under the induction by bacterial products, pro-inflammatory cytokines and stress hormone glucocorticoids, SAA may exert tissue-specific effects as a toll-like receptor 4 (TLR4)-sensed DAMP molecule. SAA may promote parturition through stimulation of inflammatory reactions via induction of pro-inflammatory cytokines, chemokines, adhesion molecules and prostaglandins in the uterus, fetal membranes and placenta. In the fetal membranes, SAA may also facilitate membrane rupture through induction of matrix metalloproteases (MMPs)- and autophagy-mediated collagen breakdown and attenuation of lysyl oxidase-mediated collagen cross-linking. SAA synthesized in extravillous trophoblasts may promote their invasiveness into the endometrium in placentation. Here, we summarized the current understanding of SAA in pregnancy with an aim to stimulate in-depth investigation of SAA in pregnancy, which may help better understand how inflammation is initiated in gestational tissues in both normal and abnormal pregnancies.