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Abstract Endocrine therapy is standard for hormone receptor–positive (HR+) breast cancer treatment. However, current strategies targeting estrogen signaling pay little attention to estradiol metabolism in the liver and is usually challenged by treatment failure. In a previous study, we demonstrated that the natural compound naringenin (NAR) inhibited HR+ breast cancer growth by activating estrogen sulfotransferase (EST) expression in the liver. Nevertheless, the poor water solubility, low bio-barrier permeability, and non-specific distribution limited its clinical application, particularly for oral administration. Here, a novel nano endocrine drug NAR-cell penetrating peptide-galactose nanoparticles (NCG) is reported. We demonstrated that NCG presented specific liver targeting and increased intestinal barrier permeability in both cell and zebrafish xenotransplantation models. Furthermore, NCG showed liver targeting and enterohepatic circulation in mouse breast cancer xenografts following oral administration. Notably, the cancer inhibition efficacy of NCG was superior to that of both NAR and the positive control tamoxifen, and was accompanied by increased hepatic EST expression and reduced estradiol levels in the liver, blood, and tumor tissue. Moreover, few side effects were observed after NCG treatment. Our findings reveal NCG as a promising candidate for endocrine therapy and highlight hepatic EST targeting as a novel therapeutic strategy for HR+ breast cancer. Graphical Abstract

The ionospheric F2 critical frequency (foF2) is one of the most crucial application parameters in high-frequency communication, detection, and electronic warfare. To improve the accuracy of spatial reconstruction of the ionospheric foF2, we propose a high-accuracy surface (HAS) modeling method. This method converts difficult-to-solve differential equations into more manageable algebraic equations using direct difference approximation, significantly reducing algorithm complexity and computational load while exhibiting excellent convergence properties. We used seven stations in Brisbane, Canberra, Darwin, Hobart, Learmonth, Perth, and Townsville, with one station as a validation station and six as training stations (e.g., Brisbane as a validation station and the other stations—Canberra, Darwin, Hobart, Learmonth, Perth, and Townsville—as training stations). The training stations and the HAS method were used to train and reconstruct the validation stations at different solar activity periods, seasons, and local times. The predicted values of the validation stations were compared with the measured values, and the proposed method was analyzed and validated. The reconstruction results show the following. (1) The relative root mean square errors (RRMSEs) of HAS method prediction in different solar activity epochs were 13.67%, 7.74%, and 9.19%, respectively, which are 13.57%, 7.41%, and 6.41% higher than the prediction accuracy of the Kriging method, respectively. (2) In the four seasons, the RRMSEs of the HAS method prediction are 9.27%, 13.1%, 8.81%, and 8.09%, respectively, which are 10.83%, 11.73%, 4.25%, and 12.00% higher than the prediction accuracy of the Kriging method. (c) During the daytime and nighttime, the RRMSEs of HAS method prediction were 9.23% and 11.17%, which were 5.92% and 11.99% higher than the prediction accuracy of the Kriging method, respectively. (d) Under the validation dataset, the average predictive RRMSE of the HAS method was 10.29%, and the average predictive RRMSE of the IRI prediction model was 12.35%, with a 2.06% improvement in the predictive accuracy of the HAS method. In general, the prediction effect of the HAS method was better than that of the Kriging method, thus verifying the effectiveness and reliability of the proposed method. In summary, the proposed reconstruction method is of great significance for improving usable frequency prediction and enhancing communication performance.

Low-frequency communication constitutes a vital component of essential communication systems, serving a pivotal role in remote radio communication, navigation, timing, and seismic analysis. To enhance the predictive precision of low-frequency skywave propagation and address the demands of engineering applications, we propose a high-precision prediction method based on the ITU-R P.684 wave-hop theory and real-time environmental parameter forecasts. This method features several distinctive attributes. Firstly, it employs real-time ionospheric prediction data instead of relying on long-term ionospheric model predictions. Secondly, it utilizes a detailed map of land–sea surface electrical characteristics, surpassing the simplistic land–sea dichotomy previously employed. Compared with measured data, the findings demonstrate that we attained a reasonable propagation pattern and achieved high-precision field strength predictions. Comparatively, the improved method exhibits an improvement in the time and spatial domains over the ITU-R P.684 standard. Finally, the improved method balances computational efficiency with enhanced prediction accuracy, supporting the advancement of low-frequency communication system design and performance evaluation.

Depression is often associated with fatigue/energy loss. However, we lack a detailed understanding of the factors explaining this association. In this study, we uncovered that depressed mice have a defect in fat absorption, resulting in weight loss and reduced circulating lipid levels. Si-Ni-San (SNS), a basic formula of traditional Chinese medicine (TCM) for the treatment of depression, was found to not only alleviate depression-like behaviors, but also reverse the weight loss and dietary fat absorption of depressed mice. We found that SNS improved body weight and circulating lipid levels of depressed mice by up-regulating proteins [such as FFA uptake protein (CD36), TAG synthesis proteins (GPAT3, MOGAT2, DGAT1 and DGAT2) and chylomicron packaging proteins (MTP and APOB)] in the fat absorption pathway. Furthermore, cell-based results conducted with LPS-stimulated mouse MODE-K and human Caco-2 cells support that SNS, as well as Sinensetin (SIN) and Nobiletin (NOB), the two active components of the formula, have a role in regulating lipid absorption. Mechanistic studies revealed that SNS reverses body weight and fat absorption defects of depressed mice in part through the NR1D1/BMAL1/DGAT2 axis. These findings advance our understanding of the crosstalk between depression and energy loss, highlight the importance of gut function in disease management, and provide a basis for the application of SNS in the clinical treatment of depression and related disorders.

Abstract Policy analysis provides multiple methods and tools for generating and transforming policy-relevant information and supporting policy evolution to address emerging social problems. In this study, a bibliometric analysis of a large number of studies on historical policy analysis was performed to provide a comprehensive understanding of the distribution and evolution of policy problems in different fields among countries. The analysis indicates that policy analysis has been a great concern for scholars in recent two decades, and is involved in multiple disciplines, among which the dominant ones are medicine, environment, energy and economy. The major concerns of policy analysts and scholars are human health needs, environmental pressures, energy consumption caused by economic growth and urbanization, and the resulting demand for sustainable development. The multidisciplinary dialog implies the complicated real-world social problems that calls for more endeavors to develop a harmonious society. A global profiling for policy analysis demonstrates that the central policy problems and the corresponding options align with national development, for example, developing countries represented by China are faced with greater environmental pressures after experiencing extensive economic growth, while developed countries such as the USA and the UK pay more attention to the social issues of health and economic transformation. Exploring the differences in policy priorities among countries can provide a new inspiration for further dialog and cooperation on the development of the international community in the future.

This paper proposes a short-term forecasting method for high-frequency broadcast Maximum Usable Frequency (MUF) based on Long Short-Term Memory (LSTM) to meet the demand for refined and precise high-frequency broadcast coverage. Based on the existing infrastructure of broadcast and television stations, we established an experimental verification system to collect data for approximately three years. Two links were selected based on data quality: Urumqi to Lhasa and Lanzhou to Lhasa. A short-term forecast of MUF was conducted using the data from these two links. Comparison and analysis were conducted between the forecasting results of our model and those of the REC533 model. Our proposed method outperforms the REC533 forecasting results overall, with a reduction in root mean square error (RMSE) of 0.66 MHz and an improvement in forecast accuracy of 14.77%. The comparison result demonstrates the feasibility and accuracy of our model.

BackgroundGlobally, the burden of breast cancer has increased significantly in recent decades. Emerging evidence suggested that endocrine-disrupting chemicals (EDCs), which have the potential to interfere with the function of normal hormones, may play a crucial role in this trend. However, the potential relationships were inconsistent in various studies.Objective and search methodsIn our study, we sought to fully evaluate the currently available epidemiological evidence to ascertain whether certain EDC congeners and their metabolites are related to breast cancer risk. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we conducted a comprehensive literature search of original peer-reviewed publications in three electronic databases: PubMed, Web of Science, and Embase. Publications that covered xenobiotic EDC exposures and breast cancer–confirmed histological results or antecedent medical records or reporting to health registers were taken into consideration.OutcomesThe final result of the literature search was 6,498 references, out which we found 67 publications that matched the requirements for meta-analysis and eight publications for qualitative trend synthesis. In this meta-analysis, statistically significant associations revealed that (i) 1-chloro-4-[2,2,2-trichloro-1-(4-chlorophenyl)ethyl]benzene (p,p'-DDT) and its major metabolite 2,2-bis(4-chlorophenyl)-1,1-dichloroethylene (p,p'-DDE) were somewhat related to a greater risk of breast cancer. However, this relationship only existed in blood serum but not in adipose tissue. (ii) Breast cancer risk was increased by exposure to chlordane and hexachlorocyclohexane. (iii) Five polychlorinated biphenyls (PCB 99, PCB 105, PCB 118, PCB 138, and PCB 183) can increase the risk of breast cancer. (iv) One phthalate congener (BBP) and one per- and polyfluoroalkyl substance congener (PFDoDA) were negatively associated with breast cancer risk. Unfortunately, heterogeneity was not well explained in our review, and a limited number of available prospective studies investigating the associations between EDC exposure and breast cancer were included in our meta-analysis. To elucidate the overall associations, future large, longitudinal epidemiological investigations are needed.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD 42023420927.

Background: Early life stress (ELS) is a major risk factor for depression in adolescents. The nucleus accumbens (NAc) is a key center of the reward system, and spine remodeling in the NAc contributes to the development of depression. The Si-Ni-San formula (SNS) is a fundamental prescription for treating depression in traditional Chinese medicine. However, little is known about the effects of SNS on behavioral abnormalities and spine plasticity in the NAc induced by ELS.Purpose: This study aimed to investigate the therapeutic effect and the modulatory mechanism of SNS on abnormal behaviors and spine plasticity in the NAc caused by ELS.Methods: We utilized a model of ELS that involved maternal separation with early weaning to explore the protective effects of SNS on adolescent depression. Depressive-like behaviors were evaluated by the sucrose preference test, the tail suspension test, and the forced swimming test; anxiety-like behaviors were monitored by the open field test and the elevated plus maze. A laser scanning confocal microscope was used to analyze dendritic spine remodeling in the NAc. The activity of Rac1 was detected by pull-down and Western blot tests. Viral-mediated gene transfer of Rac1 was used to investigate its role in ELS-induced depression-like behaviors in adolescence.Results: ELS induced depression-like behaviors but not anxiety-like behaviors in adolescent mice, accompanied by an increase in stubby spine density, a decrease in mushroom spine density, and decreased Rac1 activity in the NAc. Overexpression of constitutively active Rac1 in the NAc reversed depression-related behaviors, leading to a decrease in stubby spine density and an increase in mushroom spine density. Moreover, SNS attenuated depression-like behavior in adolescent mice and counteracted the spine abnormalities in the NAc induced by ELS. Additionally, SNS increased NAc Rac1 activity, and the inhibition of Rac1 activity weakened the antidepressant effect of SNS.Conclusion: These results suggest that SNS may exert its antidepressant effects by modulating Rac1 activity and associated spine plasticity in the NAc.

IntroductionLymph node metastasis in patients with papillary thyroid carcinoma (PTC) is associated with postoperative recurrence. Recently, most studies have focused on the evaluation of recurrence in patients with late-stage PTC, with limited data on those with early-stage PTC. We aimed to assess the relationship between lymph node ratio (LNR) and recurrence in low-to-intermediate-risk patients and validate its diagnostic efficiency in both structural (STR) and biochemical recurrence (BIR).MethodsClinical data of patients with PTC diagnosed at the Affiliated Hospital of Jining Medical University were retrospectively collected. The optimal LNR cut-off values for disease-free survival (DFS) were determined using X-tile software. Predictors were validated using univariate and multivariate Cox regression analyses.ResultsLNR had a higher diagnostic effectiveness than metastatic lymph nodes in patients with low-to-intermediate recurrence risk N1a PTC. The optimal LNR cutoff values for STR and BIR were 0.75 and 0.80, respectively. Multivariate Cox regression analysis showed that LNR≥0.75 and LNR≥0.80 were independent factors for STR and BIR, respectively. The 5-year DFS was 90.5% in the high LNR (≥0.75) and 96.8% in low LNR (

A bench–scale experiment was performed to assess whether union use of ferrate (Fe(VI)) and ferric (Fe(III)) addition in real surface water (reservoir and river water) resulted in better water remediation. The results indicated that increased Fe dosage improved the treatment performance, the removals of total coliform, turbidity and DOC were better when the mass ratio of Fe(VI): Fe(III) was 1:2 and pH was 8, regardless of the water source. Alkalescency condition benefits Fe(III) coagulation and Fe(VI) disinfection efficiency due to the better stability and greater exposure to Fe(VI). Union use of Fe(VI) and Fe(III), as a coagulant and oxidant to enhance flocculation precipitation, can simultaneously remove turbidity, degraded natural organic matter (NOM) degradation, and destroy bacterial activity. At optimized dosage and pH, chemical oxidation plays the dominant role in the disinfection performance and secondary removal of DOC for Fe(VI) treatment, while for the mechanisms of Fe(III), coagulation and adsorption make the dominant contribution to the removal of turbidity and DOC. The application of the optimal ratio can maximize the advantages of both Fe(VI) and Fe(III), and enables the maximum purification effectiveness at minimum dosage and cost, so it will be a simple and efficient treatment for different drinking water. HIGHLIGHTS Alkalescency condition benefits Fe(III) coagulation and Fe(VI) disinfection efficiency due to the better stability and greater exposure to Fe(VI).; The application of the optimal ratio can maximize the advantages of both Fe(VI) and Fe(III), and enables the maximum purification effectiveness at minimum dosage and cost.;

The height of the F2 peak electron density (hmF2) is an essential parameter in studying ionospheric electrodynamics and high-frequency wireless communication. Based on ionosphere ray propagation theory, the physical relationship between M3000F2 and hmF2 is derived and visualized. Furthermore, based on the above physical theory and the machine learning method, this paper proposes a new model for determining hmF2 using propagation factor at a distance of 3000 km from the ionospheric F2 layer, time, and season. This proposed model is easy to understand and has the characteristics of clear principles, simple structure, and easy application. Furthermore, we used six stations in east Asia to verify this model and compare it with the other three models of the International Reference Ionosphere (IRI) model. The results show that the proposed model (PRO) has minor error and higher accuracy. Specifically the RMSE of the BSE, AMTB, SHU, and the PRO models were 20.35 km, 31.51 km, 13.59 km, and 5.68 km, respectively, and the RRMSE of the BSE, AMTB, SHU, and PRO models were 8.17%, 11.88%, 4.96%, and 2.12%, respectively. In addition, the experimental results show that the PRO model can better predict the trend of the hmF2 inflection point. This method can be further extended to add data sources and provide new ideas for studying the hmF2 over global regions.

Utilizing triethylenediamine (DA), 1,3-propanesultone (PS), whose ring opens during the formation of the dizwiterion-intermediate DA-2PS, and the metal chlorides XCly, where X = Sn(IV), Zn(II),Al(III), Fe(III) and Mn(II), are used for the synthesis of five kinds of acidic metal-based functionalized ionic liquid catalysts ([DA-2PS][XCly]2). Their chemical structures, thermal stability and dual acidic active site were analyzed. We investigated the performance of [DA-2PS][XCly]2 in catalyzing the esterification reaction between 2,5-furandicarboxylic acid (FDCA) and ethylene glycol (EG) to synthesize poly (ethylene 2,5-furandicarboxylate)(PEF). Among the catalysts tested, [DA-2PS][SnCl5]2 exhibited the best catalytic performance under identical process parameters, and the optimal catalyst dosage was determined to be 0.05 mol% based on FDCA. The optimal conditions for the reaction were predicted using response surface methodology: a feed ratio of EG:FDCA = 1.96:1, an esterification temperature of 219.86 °C, a polycondensation temperature of 240.04 °C and a polycondensation time of 6.3 h, with a intrinsic viscosity of 0.67 dL·g−1. The resulting PEF was experimentally verified to exhibit an intrinsic viscosity of 0.68 dL·g−1 and a number average molecular weight of 28,820 g·mol−1. Finally, the structure and thermal properties of PEF were characterized. The results confirmed that PEF possessed the correct structure, exhibited high thermal stability and demonstrated excellent thermal properties.

In the field of electronic communication warfare, accurately predicting the range and intensity of shortwave interference signals presents a significant challenge due to the complex interplay between the ionospheric parameters and the electromagnetic environment. To address this challenge, we designed a novel tool to assess the interference impact area of shortwave interference signals in a dynamically changing ionospheric environment. Considering sophisticated ionospheric radio wave propagation models and innovative spatial grid methods, this tool finishes the comprehensive spatial distribution of the interference impact area and delivers grid-based insights into the interference intensity. Furthermore, the test verification of the tool demonstrated a mean error of 8.42 dB between the measured and simulated results, underscoring the efficacy and reliability of this tool. This pioneering work is poised to make substantial contributions to the field of communication electronic warfare and holds significant promise for guiding the development of interference countermeasures.

To improve the accuracy of predicting the ionospheric critical frequency of the F2 layer (foF2), a reconstruction method for the spatial map of the ionospheric foF2 based on modified geomagnetic dip coordinates is proposed. Based on the strong correlation between the ionospheric foF2 and geomagnetic coordinates, the variation function of ionospheric distance is built. In the end, the spatial map of the ionospheric foF2 is predicted by solving the Kriging equation. The results show that the regional characteristics of the ionospheric foF2 analyzed by the proposed method are consistent with the observations. Compared with the reconstructed value of foF2 using traditional geographic coordinates, the root-mean-square error (RMSE) in high solar activity years decreased by 0.43 MHz, and the relative RMSE decreased by 5.48%; The RMSE decreased by 0.35 MHz during low solar activity which is 5.99% lower to relative RMSE. The research results provide support for high-frequency communication frequency selection.

To fully grasp the characteristics and provide a basis for establishing an evaporation duct communication system for the South China Sea (SCS), we constructed a regional statistical database based on remote sensing meteorological parameters and a numerical model. This database has the advantage of extensive spatiotemporal coverage and high resolution, which can provide accessibility and as a supplementary means for the maritime sixth Generation communication network. Specifically, work has been completed in three areas. First, the overall evaporation duct height (EDH) in the central SCS varies periodically and remains intense throughout the day, decreasing only just before sunrise during 04:00–08:00. Moreover, a 20.0 m high channel appears at the “Golden edge” in the northern coastal area, which can expand as far as 300 km from the coast during May–July. Second, the characteristics of specific regions were analyzed, and the highest average EDH was determined as 18.4 m in the Taiwan Strait. The height in the central SCS fluctuates little with monthly and annual variation, and it is maintained between 10.0 and 12.0 m. Third, based on the evaporation duct formation principle, we analyzed the spatiotemporal distributions of meteorological parameters. The Taiwan Strait maintains the highest EDH over the SCS, owing to the influence of the Kuroshio Current, and the average sea surface temperature (SST) reaches 28.41°C in June and 19.58°C in January. To the central SCS, high SST, low wind speed, and relative humidity of approximately 80% provide excellent conditions for maintaining an evaporation duct over the long term.

BackgroundThe frequency of thyroid cancer has rapidly increased in recent years globally. Thus, more papillary thyroid microcarcinoma (PTMC) patients are being diagnosed, including clinical lymph node-negative (cN0) patients. Our study attempted to develop a prediction model for assessing the probability of central lymph node metastasis (CLNM) in cN0 PTMC patients.MethodsA total of 595 patients from the Affiliated Hospital of Qingdao University (training cohort: 456 patients) and the Affiliated Hospital of Jining Medical University (verification cohort: 139 patients) who underwent thyroid surgery between January 2020 and May 2022 were enrolled in this study. Their clinical and molecular pathology data were analyzed with multivariate logistic regression to identify independent factors, and then we established a prediction model to assess the risk of CLNM in cN0 PTMC patients.ResultsMultivariate logistic regression analysis revealed that sex, Hashimoto’s thyroiditis (HT), tumor size, extrathyroidal extension, TERT promoter mutations and NRAS mutation were independent factors of CLNM. The prediction model demonstrated good discrimination ability (C-index: 0.757 and 0.753 in the derivation and validation cohorts, respectively). The calibration curve of the model was near the optimum diagonal line, and decision curve analysis (DCA) showed a noticeably better benefit.ConclusionCLNM in cN0 PTMC patients is associated with male sex, tumor size, extrathyroidal extension, HT, TERT promoter mutations and NRAS mutation. The prediction model exhibits good discrimination, calibration and clinical usefulness. This model will help to assess CLNM risk and make clinical decisions in cN0 PTMC patients.

Abstract Background A lot of medical mentions can be extracted from a huge amount of medical texts. In order to make use of these medical mentions, a prerequisite step is to link those medical mentions to a medical domain knowledge base (KB). This linkage of mention to a well-defined, unambiguous KB is a necessary part of the downstream application such as disease diagnosis and prescription of drugs. Such demand becomes more urgent in colloquial and informal situations like online medical consultation, where the medical language is more casual and vaguer. In this article, we propose an unsupervised method to link the Chinese medical symptom mentions to the ICD10 classification in a colloquial background. Methods We propose an unsupervised entity linking model using multi-instance learning (MIL). Our approach builds on a basic unsupervised entity linking method (named BEL), which is an embedding similarity-based EL model in this paper, and uses MIL training paradigm to boost the performance of BEL. First, we construct a dataset from an unlabeled large-scale Chinese medical consultation corpus with the help of BEL. Subsequently, we use a variety of encoders to obtain the representations of mention-context and the ICD10 entities. Then the representations are fed into a ranking network to score candidate entities. Results We evaluate the proposed model on the test dataset annotated by professional doctors. The evaluation results show that our method achieves 60.34% accuracy, exceeding the fundamental BEL by 1.72%. Conclusions We propose an unsupervised entity linking method to the entity linking in the medical domain, using MIL training manner. We annotate a test set for evaluation. The experimental results show that our model behaves better than the fundamental model BEL, and provides an insight for future research.

The authors demonstrate a sensing approach for effectively monitoring organic micropollutants in water. They first use mesoporous nanosponge and magnetic nanoparticles for fast enrichment of micropollutants, and demonstrate SERS-based sensing with 2-3 orders of magnitude improvement in detection limits.

Desert shrubs play important roles in desertification control and vegetation restoration, which are particularly affected by droughts caused by climate change. However, the hydraulic strategies associated with hydraulic functional traits of desert shrubs remain unclear. Here, eight desert shrub species with different life forms and morphologies were selected for a common garden experiment at the southeast edge of the Tengger Desert in northern China to study the hydraulic strategies mediated by leaf hydraulic functional traits. Diurnal leaf water potential change, leaf hydraulic efficiency and safety, hydraulic safety margin, hydraulic capacitance, and water potential and relative water content at the turgor loss point were observed to significantly differ among species, suggesting that leaf hydraulic functional traits were strongly associated with species even when living in the same environment. Additionally, shrubs with greater leaf hydraulic efficiency had lower midday leaf water potential and leaf hydraulic safety, suggesting that leaf hydraulic efficiency had a strong trade-off with hydraulic safety and minimum leaf water potential, whereas there was also a coordination between leaf hydraulic safety and the leaf minimal water potential. Moreover, shrubs with higher leaf hydraulic capacitance had greater hydraulic safety margins, indicating coordination between leaf hydraulic capacitance and hydraulic safety margin. Overall, this study indicated that minimal daily leaf water potential, as an easily measured parameter, may be used preliminarily to predict leaf hydraulic conductivity and the resistance to embolism of desert shrubs, providing critical insights into hydraulic trade-off and coordination strategies for native shrubs as priority species in desert vegetation restoration and reconstruction.

Early-life stress (ELS) was found to increase the risk of adolescent depression, and clinical evidence indicated that eicosapentaenoic acid (EPA) was decreased in patients with adolescent depression, but the underlying mechanisms are unclear. Here, we utilized an ELS model of maternal separation with early weaning to explore the protective role of EPA in adolescent depression. We found that that ELS induced depression-like behavior rather than anxiety-like behavior in adolescent mice. RNA-sequencing results showed that ELS changed the transcription pattern in the liver, including 863 upregulated genes and 971 downregulated genes, especially those related to the biosynthesis of unsaturated fatty acids metabolism in the liver. Moreover, ELS decreased the expression of the rate-limiting enzymes, fatty acid desaturases 1/2 (FADS1/2), involved in the biosynthesis of EPA in the liver. Additionally, ELS reduced the levels of EPA in the liver, serum, and hippocampus, and EPA administration improved depression-like behavior-induced by ELS. Our results provide transcriptomic evidence that ELS increases the risk of adolescent depression by reducing the synthesis of unsaturated fatty acids in the liver, especially EPA, and suggest that supplementation with EPA should be investigated as a potential treatment for adolescent depression.

The ionospheric F2 layer is the essential layer in the propagation of high-frequency radio waves, and the peak electron density height of the ionospheric F2 layer (hmF2) is one of the important parameters. To improve the predicted accuracy of hmF2 for further improving the ability of HF skywave propagation prediction and communication frequency selection, we present an interpretable long-term prediction model of hmF2 using the statistical machine learning (SML) method. Taking Moscow station as an example, this method has been tested using the ionospheric observation data from August 2011 to October 2016. Only by inputting sunspot number, month, and universal time into the proposed model can the predicted value of hmF2 be obtained for the corresponding time. Finally, we compare the predicted results of the proposed model with those of the International Reference Ionospheric (IRI) model to verify its stability and reliability. The result shows that, compared with the IRI model, the predicted average statistical RMSE decreased by 5.20 km, and RRMSE decreased by 1.78%. This method is expected to provide ionospheric parameter prediction accuracy on a global scale.

Plant root hydraulic redistribution (HR) has been widely recognized as a phenomenon that helps alleviate vegetation drought stress. However, a systematic assessment of the magnitude of HR and its drivers at the global scale are lacking. We collected 37 peer-reviewed papers (comprising 47 research sites) published in 1900–2018 and comprehensively analyzed the magnitude of HR and its underlying factors. We used a weighting method to analyze HR magnitude and its effect on plant transpiration. Machine learning algorithms (boosted regression trees) and structural equation modeling were used to determine the influence of each factor on HR magnitude. We found that the magnitude of HR was 0.249 mm H2O d−1 (95% CI, 0.113–0.384) and its contribution to plant transpiration was 27.4% (3–79%). HR varied significantly among different terrestrial biomes and mainly occurred in forests with drier conditions, such as temperate forest ecosystems (HR = 0.502 mm H2O d−1), where HR was significantly higher than in other ecosystems (p < 0.01). The magnitude of HR in angiosperms was significantly higher than that in gymnosperms (p < 0.05). The mean magnitude of HR first increased and then decreased with an increase in humidity index; conversely, the mean magnitude of HR decreased with an increase in water table depth. HR was significantly positively correlated with root length and transpiration. Plant characteristics and environmental factors jointly accounted for 61.0% of the variation in HR, and plant transpiration was the major factor that directly influenced HR (43.1% relative importance; p < 0.001), and soil texture was an important indirect driver of HR. Our synthesis offers a comprehensive perspective of how plant characteristics and environmental factors influence HR magnitude.

In this study, we aim to analyze the electromagnetic interference (EMI) regarding the Five-hundred-meter Aperture Spherical radio Telescope (FAST) caused by base stations in the International Mobile Telecommunications-2000 (IMT-2000) frequency band. By analyzing the frequency bands used by the transmitting and receiving devices and the surrounding environmental parameters and utilizing an approach to predicting radio wave propagation loss that is based on deterministic methods, we conclude by comparing the predicted received power at the FAST with its interference protection threshold. Our analysis demonstrates that, currently, only 55.31% of IMT-2000 base stations in the FAST radio quiet zone (RQZ) meet the protection threshold. Additionally, this article verifies the applicability and accuracy of the radio wave propagation model used in the research based on field strength measurements. Overall, this study provides valuable insights for improving the electromagnetic environment surrounding FAST and reducing the EMI caused by mobile communication base stations. It also provides corresponding analysis methods and useful suggestions for analyzing electromagnetic radiation interference in other radio telescopes.

Abstract Background Photosystem II (PSII) is a highly conserved integral-membrane multi-subunit pigment-protein complex. The proteins, pigments, lipids, and ions in PSII need to be assembled precisely to ensure a proper PSII biogenesis. D1 is the main subunit of PSII core reaction center (RC), and is usually synthesized as a precursor D1. D1 maturation by the C-terminal processing protease CtpA is essential for PSII assembly. However, the detailed mechanism about how D1 maturation affects PSII assembly is not clearly elucidated so far. In this study, Arabidopsis thaliana CtpA mutant (atctpa: SALK_056011), which lacks the D1 mature process, was used to investigate the function of this process on PSII assembly in more details. Results Without the C-terminal processing of precursor D1, PSII assembly, including PSII monomer, dimer, especially PSII supercomplexes (PSII SCs), was largely compromised as reported previously. Western blotting following the BN-2D-SDS PAGE revealed that although the assembly of PSII core proteins D2, CP43 and CP47 was affected by the loss of D1 mature process, the incorporation of CP43 was affected the most, indicated by its most reduced assembly efficiency into PSII SCs. Furthermore, the slower growth of yeast cells which were co-transformed with pD1 and CP43, when compared with the ones co-transformed with mature D1 and CP43, approved the existence of D1 C-terminal tail hindered the interaction efficiency between D1 and CP43, indicating the physiological importance of D1 mature process on the PSII assembly and the healthy growth of the organisms. Conclusions The knockout Arabidopsis atctpa mutant is a good material to study the unexpected link between D1 maturation and PSII SCs assembly. The loss of D1 maturation mainly affects the incorporation of PSII core protein CP43, an inner antenna binding protein, which functions in the association of LHCII complexes to PSII dimers during the formation of PSII SCs. Our findings here provide detailed supports of the role of D1 maturation during PSII SCs assembly in higher plants.

BackgroundChildhood maltreatment is known as a significant risk factor for later depression. However, there remains a lack of understanding about the mechanisms through which childhood maltreatment confers risk for depression. This study explores how Qi-stagnation constitution (QSC) and emotion regulation affect the link between childhood maltreatment and depressive symptoms in Chinese college students.MethodsWe recruited 2,108 college students aged 18–25 years between November 2020 and December 2021. Participants were required to complete four self-report questionnaires, including the Childhood Trauma Questionnaire-Short Form (CTQ-SF), Qi-Stagnation Constitution (QSC) subscale of the simplified Chinese Medicine Constitution Questionnaire, Difficulties in Emotion Regulation Scale (DERS), and the Beck Depression Inventory-II (BDI-II). Moderated mediation analyses were conducted.ResultsThere was a positive correlation between childhood maltreatment and QSC, while the QSC partially mediated the effect of childhood maltreatment on depressive scores in college students. In addition, emotion dysregulation moderated the association between QSC and depressive scores.ConclusionThese results enhance understanding of key factors influencing the link between childhood maltreatment and depressive symptoms among college students by combining the theory of TCM constitution with psychological processes. The development of strategies to prevent biased Qi-stagnation constitution and emotion dysregulation may help to improve college students’ mental health and strengthen the resilience of individuals to depression.

The dorsal raphe nucleus (DRN) is a major source of serotonin in the central nervous system, which is closely related to depression-like behaviors and is modulated by local GABAergic interneurons. Although serotonin neurons are known to be activated by struggling behavior in tail suspension test (TST), the exact electrophysiological characteristics are still unclear. Here, we combined in vivo electrode recording and behavioral test to explore the mice neuron electrophysiology in DRN during TST and observed that gamma oscillation was related to despair-like behaviors whereas burst fraction was crucial for survival-like behaviors. We reported the identification of a subpopulation of DRN neurons which change their firing rates when mice get into and during TST immobile states. Both increase (putative despair units, D units for short) and decrease (putative survival units, S units for short) in firing rate were observed. Furthermore, using optogenetics to identify parvalbumin-positive (PV+) and serotonin transporter-positive (SERT+) neurons, we found that SERT+ neurons were almost S units. Interestingly, those that have been identified PV+ neurons include ~20% of D units and ~50% of S units. These results suggest that electrophysiological characteristics incorporated in despair-like behavior studies can provide new insight into the study of anti-depression targets, and GABAergic interneuron is a complex key hub to the coding and regulation of local neural network.

Saline-alkali stress seriously restricts rice growth, development, and production in northern China. The damage of alkaline stress on rice is much greater than that of salt due to ion toxicity, osmotic stress, and especially high pH. As a signal molecule, melatonin (N-acetyl-5-methoxytryptamine, MT) mediates many physiological processes in rice and participates in protecting rice from abiotic stress. The potential mechanism of exogenous melatonin-mediated alkaline stress tolerance is still largely unknown. In this study, the effects of melatonin on the morphological change, physiological property, and corresponding genes expression in rice seedlings were analyzed under alkaline stress (20 mmol L−1, pH 9.55). The results showed that the expression levels of MT synthesis genes (TDC2, T5H, SNAT, ASMT1, and ASMT2) were induced by both exogenous MT and alkaline stress treatment. The cell membrane was protected by MT, and the MT furtherly play role in scavenging reactive oxygen species (ROS), reducing lipoxygenase (LOX) activity, and malondialdehyde (MDA) content. The scavenging of ROS by melatonin is attributed to the coupling of the improvement of redox homeostasis and the enhancement of antioxidant enzyme activity and antioxidant content by upregulating the transcriptional levels of antioxidase genes. In the meantime, MT pretreatment promoted the accumulation of free proline, sucrose, and fructose by regulating the OsP5CS, OsSUS7, and OsSPS1 gene expression level and increased chlorophyll content upregulating the expression of chlorophyll synthesis-related genes. Ultimately, the alleviating effect of exogenous melatonin on alkaline stress was reflected in increasing the leaf relative water content (RWC) and root-shoot ratio and reducing the leaf tip wilt index (TWI) through a series of physiological and biochemical changes. Melatonin pretreatment changed the expression level of MT synthesis genes which might contribute to MT synthesis in rice, consequently, activated the ROS scavenging system and alleviating the damage of alkaline stress on rice seedlings. Our study comprehensively understands the alleviating effect of exogenous melatonin on rice under alkaline stress.

Abstract Objective To clarify the distribution of lorlatinib in the brain and elucidate the molecular mechanisms of lorlatinib penetration across the blood‐brain barrier (BBB). Methods Cytological experiments were performed to investigate the growth inhibitory effect of lorlatinib on different cells (endothelial cells HUVEC, HMEC‐1, and HCMEC/D3) and to investigate the protective effect of lorlatinib on neuronal cells after SH‐SY5Y hypoxia/reoxygenation injury. Furthermore, rat brain tissue was sequenced, and the differentially expressed genes (secreted phosphoprotein 1 (SPP1), vascular endothelial growth factor (VEGF), transforming growth factor beta (TGF‐β), Claudin, ZO‐1 and P‐gp) in several different drug treatment groups were verified by Real‐Time PCR. Lorlatinib brain distribution was predicted by physiologically based pharmacokinetics (PBPK). Results Lorlatinib and crizotinib both had inhibitory effects on endothelial cells, however lorlatinib inhibited the growth of HCMEC/D3 more efficaciously than crizotinib. In the SH‐SY5Y hypoxia model, lorlatinib had a greater protective effect on nerve cell damage caused by hypoxia and reoxygenation than crizotinib. The expression of SPP1, VEGF, TGF‐β, and Claudin in brain tissue was significantly downregulated after lorlatinib administration, and the expression level of early growth transcription factor 1 (Egr‐1) was significantly increased. The PBPK model successfully described lorlatinib concentrations in blood and brain tissue in the mouse model and gave a brain tissue partition coefficient of 0.7. Conclusion Lorlatinib can increase the permeability of the blood‐brain barrier whereby we suggest its underlying working mechanism is related to downregulating SPP1, inhibiting VEGF, TGF‐β, and Claudin subsequently reducing the number of tight junctions between BBB cells. Lorlatinib plays a protective role on injured nerve cells and does not change the amount of P‐gp expression in brain tissue, which may be important for its ability to be efficacious across the BBB with a low incidence of resistance.

To further improve the prediction accuracy of the critical frequency of the ionospheric F2 layer (foF2), we use the machine learning method (ML) to establish an explanatory dynamic model to predict foF2. Firstly, according to the ML modeling process, the three elements of establishing a prediction model of foF2 and four problems to be solved are determined, and the idea and concrete steps of model building are determined. Then the data collection is explained in detail, and according to the modeling process, foF2 dynamic change mapping and its parameters are determined in turn. Finally, the established model is compared with the International Reference Ionospheric model (IRI-2016) and the Asian Regional foF2 Model (ARFM) to verify the validity and reliability. The results show that compared with the IRI-URSI, IRI-CCIR, and ARFM models, the statistical average error of the established model decreased by 0.316 MHz, 0.132 MHz, and 0.007 MHz, respectively. Further, the statistical average relative root-mean-square error decreased by 9.62%, 4.05%, and 0.15%, respectively.

A natural hybrid filler (silica carbon black, name as SiCB) containing biochar and silica, was prepared from pyrolytic rice husk, and incorporated into natural rubber matrix. SiCB product exhibited very unique natural hybrid interface structure, which endows SiCB multiple-functional roles. It can act as good reinforcing filler to enhance mechanical properties and provide strong interfacial polarizability and dipole polarizability. As a result, when the content of SiCB was enhanced to 20 phr (parts per hundred of rubber), the tensile strength of the natural rubber composites was largely increased up to 30.28 MPa, which was two time higher to that of pure NR (15MPa). The dielectric constant at 103 Hz of the composites filled with 60 phr SiCB reached 7.62, which was 2.4 times of that of pure NR, because of the simultaneously improved interfacial and dipole polarizability. Moreover, the dielectric loss of all these composites at 103 Hz remained lower than 0.05. This work provides a simple and nontoxic method to prepare a sustainable natural hybrid filler and explore its novel application. Comparing with the rice husk ash, it can enhance the mechanical and electrical properties of the rubber composites at the same time. This will greatly expand the application of such biomass-based composite materials and this renewable resource.

Chronic psychological stress is closely correlated with breast cancer growth and metastasis. Sini San (SNS) formula is a classical prescription for relieving depression-related symptoms in traditional Chinese medicine (TCM). Current researches have suggested that chronic psychological stress is closely correlated with cancer stem cells (CSCs) and endoplasmic reticulum (ER) stress. This study aimed to investigate the effects of chronic psychological stress on ER stress-mediated breast cancer stemness and the therapeutic implication of SNS. Chronic psychological stress promoted lung metastasis in 4T1 breast tumor-bearing mice and increased the stem cell-like populations and stemness-related gene expression. Meanwhile, GRP78, a marker of ER stress, was significantly increased in the breast tumors and lung metastases under chronic psychological stress. As a biochemical hallmark of chronic psychological stress, cortisol dramatically enhanced the stem cell-like populations and mammospheres formation by activating GRP78 transcriptionally. However, GRP78 inhibitors or shRNA attenuated the stemness enhancement mediated by cortisol. Similarly, SNS inhibited chronic psychological stress-induced lung metastasis and stemness of breast cancer cells, as well as reversed cortisol-induced stem cell-like populations and mammospheres formation by attenuating GRP78 expression. Co-localization and co-immunoprecipitation experiments showed that SNS interrupted the interaction between GRP78 and LRP5 on the cell surface, thus inhibiting the Wnt/β-catenin signaling of breast CSCs. Altogether, this study not only uncovers the biological influence and molecular mechanism of chronic psychological stress on breast CSCs but also highlights SNS as a promising strategy for relieving GRP78-induced breast cancer stemness via inhibiting GRP78 activation.

Abstract More and more evidence show that major depressive disorder (MDD) is closely related to inflammation caused by chronic stress, which seriously affects human physical and mental health. However, the inflammatory mechanism of depression and its effect on brain function have not been clarified. Based on resting‐state functional magnetic resonance imaging (rs‐fMRI), we investigated change of brain functional imaging and the inflammatory mechanism of damage‐related molecular patterns (DAMPs)—receptor of advanced glycation protein end product (RAGE) in MDD patients and depressive‐like cynomolgus monkeys and mice models induced by chronic stress. The regional homogeneity (ReHo) and functional connectivity (FC) were analyzed using MATLAB and SPM12 software. We detected the expression of DAMPs‐RAGE pathway‐related proteins and mRNA in MDD peripheral blood and in serum and brain tissue of cynomolgus monkeys and mice. Meanwhile, RAGE gene knockout mice, RAGE inhibitor, and overexpression of AVV9RAGE adeno‐associated virus were used to verify that RAGE is a reliable potential biomarker of depression. The results showed that the ReHo value of prefrontal cortex (PFC) in MDD patients and depressive‐like cynomolgus monkeys was decreased. Then, the PFC was used as a seed point, the FC of ipsilateral and contralateral PFC were weakened in depressive‐like mice. At the same time, qPCR showed that RAGE and HMGB1 mRNA were upregulated and S100β mRNA was downregulated. The expression of RAGE‐related inflammatory protein in PFC of depressive‐like monkeys and mice were consistent with that in peripheral blood of MDD patients. Moreover, the results were confirmed in RAGE–/– mice, injection of FPS‐ZM1, and overexpression of AAV9RAGE in mice. To sum up, our findings enhance the evidence that chronic stress‐PFC‐RAGE are associated with depression. These results attempt to establish the links between brain functional imaging, and molecular targets among different species will help to reveal the pathophysiological mechanism of depression from multiple perspectives.

Social isolation (SI) is a major risk factor for mood disorders in adolescents. The nucleus accumbens (NAc) is an important reward center implicated in psychiatric disorders. Resveratrol (RSV) is one of the most effective natural polyphenols with anti-anxiety and depression effects. However, little is known about the therapeutic effects and mechanisms of RSV on behavioral abnormality of adolescent social stress. Therefore, this study aimed to investigate the underlying mechanism of RSV on the amelioration of SI-induced behavioral abnormality. We found that SI induced anxiety-like behavior and social dysfunction in isolated female rats. Moreover, SI reduced mitochondrial number and ATP levels and increased thin spine density in the NAc. RNA sequencing results showed that SI changed the transcription pattern in the NAc, including 519 upregulated genes and 610 downregulated genes, especially those related to mitochondrial function. Importantly, RSV ameliorated behavioral and spine abnormalities induced by SI and increased NAc ATP levels and mitochondria number. Furthermore, RSV increased the activity of cytochrome C oxidase (COX) and upregulated mRNA levels of Cox5a, Cox6a1 and Cox7c. These results demonstrate that the modulation of spine plasticity and mitochondrial function in the NAc by RSV has a therapeutic effect on mood disorders induced by social isolation.

The evaporation duct height (EDH) can reflect the main characteristics of the near-surface meteorological environment, which is essential for designing a communication system under this propagation mechanism. This study proposes an EDH prediction network with multi-layer perception (MLP). Further, we construct a multi-dimensional EDH prediction model (multilayer-MLP-EDH) for the first time by adding spatial and temporal “extra data” derived from the meteorological measurements. The experimental results show that: (1) compared with the naval-postgraduate-school (NPS) model, the root-mean-square error (RMSE) of the meteorological-MLP-EDH model is reduced to 2.15 m, and the percentage improvement reached 54.00%; (2) spatial and temporal parameters can reduce the RMSE to 1.54 m with an improvement of 66.96%; (3) the multilayer-MLP- EDH model can match measurements well at both large and small scales by attaching meteorological parameters at extra height, the error is further reduced to 1.05 m, with 77.51% improvement compared with the NPS model. The proposed model can significantly improve the prediction accuracy of the EDH and has great potential to improve the communication quality, reliability, and efficiency of ducting in evaporation ducts.

Affected by the Taiwan Strait Warm Current, the evaporation intensity around the Taiwan Strait is significantly higher than in other southern and eastern coastal areas of China. To explore a new and effective method for maritime communication across the Taiwan Strait, we present a preliminary investigation of wireless microwave transmission in an evaporation duct. From 9 to 14 o’clock, the percentage of the evaporation duct height exceeding 10 m reached over 90% in 2020. With the favorable channel in this period, a “straight-through propagation channel” emerged, with a serviceable ratio of 99.00% at a 300 km transmission range. The high-quality transmission with BPSK modulation occurred 98.90% of the year from 12 to 13 o’clock, with 89.89% of the signal-to-noise ratio (SNR) exceeding 90 dB. Based on the effective use of the evaporation duct, the proposed method can provide favorable support for maritime applications across the Taiwan Strait.

Lung cancer ranks as a leading cause of death. Although targeted therapies usually trigger profound initial patient responses, these effects are transient due to drug resistance and severe side effects. Xihuang Pill (XHW) is a popular Chinese medicine formula that might benefit cancer patients when used as a complementary therapy. However, its underlying mechanism when combined with anticancer drugs is not clearly understood. Here, we used an integrated strategy to reveal the regulatory properties of XHW in increasing the antitumor activity of anlotinib in lung cancer. We evaluated the anti-lung cancer effect of XHW combined with anlotinib in mice bearing Lewis lung carcinoma (LLC). We applied untargeted metabolomics to identify the differences metabolism and found that XHW improved the effects of anlotinib on lung cancer. The components and targets related to the effects of XHW treatment on lung cancer were obtained through network pharmacology. Then, by integrating the biologically active components of XHW and anlotinib as well as the treatment-responsive metabolites and their related targets, an interaction network was constructed to evaluate the combination therapy. Finally, important protein candidates for this response were verified by immunohistochemistry of tumor tissues. The results showed that XHW significantly improved the inhibitory effect of anlotinib on tumor growth in LLC-bearing mice. Additionally, 12 differentially-abundant metabolites were identified by untargeted metabolomics in the XHW/anlotinib group compared with the XHW or anlotinib groups, and they were mainly enriched in fatty acid metabolism, lipid metabolism and amino acid metabolism pathways. Anlotinib, 23 components in Shexiang, 2 components in Niuhuang, 30 components in Ruxiang and 60 components in Moyao work together to act on 30 targets to regulate hexadecanoic acid (also named palmitic acid), linoleic acid, lactosylceramide, adrenaline, arachidonic acid and lysoPC(18:1(9Z)). The results of immunohistochemistry showed that XHW combined with anlotinib reduced the expression of PDGFRA in tumors. Overall, the key metabolites of XHW that enhances the efficacy of anlotinib were regulated by a multicomponent and multitarget interaction network. Our results suggested that anlotinib combined with XHW may be a promising strategy for the treatment of lung cancer.

Of late, lorlatinib has played an increasingly pivotal role in the treatment of brain metastasis from non-small cell lung cancer. However, its pharmacokinetics in the brain and the mechanism of entry are still controversial. The purpose of this study was to explore the mechanisms of brain penetration by lorlatinib and identify potential biomarkers for the prediction of lorlatinib concentration in the brain. Detection of lorlatinib in lorlatinib-administered mice and control mice was performed using liquid chromatography and mass spectrometry. Metabolomics and transcriptomics were combined to investigate the pathway and relationships between metabolites and genes. Multilayer perceptron was applied to construct an artificial neural network model for prediction of the distribution of lorlatinib in the brain. Nine biomarkers related to lorlatinib concentration in the brain were identified. A metabolite-reaction-enzyme-gene interaction network was built to reveal the mechanism of lorlatinib. A multilayer perceptron model based on the identified biomarkers provides a prediction accuracy rate of greater than 85%. The identified biomarkers and the neural network constructed with these metabolites will be valuable for predicting the concentration of drugs in the brain. The model provides a lorlatinib to treat tumor brain metastases in the clinic.

Lung cancer remains the leading cause of cancer death worldwide, and the current therapy seems to have reached a plateau due to toxicities and acquired resistance. Therefore, exploration of novel therapeutic avenues may be useful. Si Jun Zi Tang (SJZ), a four-herb Chinese medicine formula first described approximately one thousand years, is often prescribed for cancer patients as a complementary therapy. However, whether SJZ benefits cancer patients as well as the main active constituents and its regulatory mechanism in combination with anticancer drugs remains unknown. Here, we investigated the anti-lung cancer potency and underlying mechanisms of the combination of gefitinib plus SJZ in mice with Lewis lung carcinoma (LLC), using histopathology and an integrated strategy of metabolomics and network pharmacology. The results showed that SJZ significantly enhanced gefitinib suppressing tumor growth and inhibiting LLC metastasis in LLC-bearing mice. Furthermore, 9 potential metabolomics biomarkers that differentially expressed in the SJZ/gefitinib group compared to the SJZ group or gefitinib group were identified by untargeted metabolomics, mainly involved three pathways: tricarboxylic acid cycle, tyrosine and tryptophan biosynthesis metabolism and linoleic acid metabolism. Five active ingredients, kaempferol, ginsenoside Rf, caprylic acid, lauric acid and naringenin, acted directly on 9 targets and regulated 4 out of 9 metabolites. Our results indicated that SJZ enhanced the anti-lung cancer effects of gefitinib via the key targets ABCG2, ABCC1, ABAT, GSR, CYP1A2, ALOX5, CYP3A4, PLA2G1B and PLA2G2A and the key metabolites 2-oxoglutarate, taurocholic acid, oxidized glutathione and linoleic acid. This work illustrated the modulatory properties of SJZ, which enhanced the anticancer effects of gefitinib, using metabolomics and network pharmacology analyses, and provided insights into underlying the mechanism the active ingredients of SJZfor the treatment of lung cancer in combination with gefitinib.

As one of the key technologies of HF communication, the maximum usable frequency (MUF) prediction method has been widely discussed. To experimentally confirm the reliability of commonly used MUFs prediction models for high-frequency communication, we have compared maximum observed frequencies (MOFs) and predicted MUFs to assess the accuracy of two typical prediction models. The root-mean-square error (RMSE) and relative RMSE (RRMSE) between oblique sounding MOFs and the predicted MUFs were used to assess the model’s accuracy. The oblique sounding path was from Changchun to Jinyang, and the vertical-sounding ionosonde was located in Beijing, which was approximately the midpoint of the oblique sounding circuit. The statistical analysis results show that: (a) the trend of prediction results from the Lockwood and the Istituto Nazionale di Geofisica e Vulcanologia (INGV) model are in good agreement with the observations: the mean RMSE and RRMSE of the INGV model are less than those of the Lockwood model; (b) in the four different periods (sunrise, daytime, sunset, and nighttime) of the whole day, the maximum difference of RMSE between the Lockwood and INGV model is 0.14 MHz (the INGV performs better than the LWM), with the corresponding differences of RRMSE being 0.31% at sunrise and 0.68% at daytime; (c) in the four seasons of spring, summer, autumn, and winter, the minimum RMSE values of the Lockwood and INGV models are 1.51 MHz and 1.37 MHz, respectively, which are obtained in winter, and the corresponding RRMSEs are 11.47% and 11.79%, respectively; (d) in the high and low solar activity epochs, the mean RMSEs of the Lockwood and INGV models are 1.63 MHz, and 1.54 MHz, with corresponding mean RRMSE values of 11.47% and 11.55%. In conclusion, the INGV model is more suitable for MUF prediction over Beijing and its adjacent mid-latitude regions from the RMSE comparison of the two models.

Our aims were to evaluate the depression model of early maternal separation (MS) combined with adolescent chronic unpredictable mild stress (CUMS) in female adult SD rats to observe the behavior and the expressions of synaptic proteins in rats and to provide a reference for the screening of antidepressant drug activity. In our study, MS and CUMS were conducted to establish a dual stress model on female rats. Behavioral tests, including the sucrose preference test, open field test, and zero maze test, were used to detect depression-like and anxiety-like behavior of animals. Nissl staining was used to detect the number of neuronal cells in the hippocampus CA1 and DG regions of rats from each group. Synaptophysin (SYN), postsynaptic density-95 (PSD-95), and growth-associated protein-43 (GAP-43) expressions in the hippocampus were detected by western blot. Expression of the hippocampus SYN protein was further detected by immunohistochemistry. Rats in the MS+CUMS group presented more serious depression-like and anxiety-like behavior than in the MS group. Also, few Nissl bodies in the hippocampus CA1 and DG regions, less percentage of SYN-positive cells, and downregulated expressions of SYN, PSD-95, and GAP43 were found in the hippocampus of rats in MS+CUMS group. In conclusion, adult female rats that underwent MS and CUMS performed more critical depression-like and anxiety-like behaviors, and this process may be resulted from synaptic plasticity impairment.

Mitochondrial transcription termination factors (mTERFs) are highly conserved proteins in metazoans. Plants have many more mTERF proteins than animals. The functions and the underlying mechanisms of plants’ mTERFs remain largely unknown. In plants, mTERF family proteins are present in both mitochondria and plastids and are involved in gene expression in these organelles through different mechanisms. In this study, we screened Arabidopsis mutants with pigment-defective phenotypes and isolated a T-DNA insertion mutant exhibiting seedling-lethal and albino phenotypes [seedling lethal 1 (sl1)]. The SL1 gene encodes an mTERF protein localized in the chloroplast stroma. The sl1 mutant showed severe defects in chloroplast development, photosystem assembly, and the accumulation of photosynthetic proteins. Furthermore, the transcript levels of some plastid-encoded proteins were significantly reduced in the mutant, suggesting that SL1/mTERF3 may function in the chloroplast gene expression. Indeed, SL1/mTERF3 interacted with PAP12/PTAC7, PAP5/PTAC12, and PAP7/PTAC14 in the subgroup of DNA/RNA metabolism in the plastid-encoded RNA polymerase (PEP) complex. Taken together, the characterization of the plant chloroplast mTERF protein, SL1/mTERF3, that associated with PEP complex proteins provided new insights into RNA transcription in the chloroplast.

Rice husk ash (RHA)-reinforced composites are now used in many tribological applications. We prepared two kinds of RHAs using different pretreatment and the same pyrolysis process, namely water-treated RHA (WRHA) and acid-treated RHA (ARHA). Comparing the two RHAs, the RHA pretreated with hydrochloric acid (HCl) was found to have a smaller particle size and a more uniform dispersion. Accordingly, the two kinds of RHAs were used as fillers and added to the high-density polyethylene (HDPE) matrix by an extrusion process. The results showed that the friction coefficient (COF) value of the composites with ARHA was reduced to 0.12 when an additional amount of 0.75 wt.% or 1.5 wt.%. WRHA was used as a filler to the amount of 1.5 wt.%, but the COF value was raised to about 0.21. The reason for this phenomenon may be due to its larger particle size and more severe abrasive wear. This work provides a method for making natural biomass fillers that can effectively reduce the COF of HDPE composites with slight decreases in mechanical properties.

Photosynthesis uses sunlight and carbon dioxide to produce biomass that is vital to all life on earth. In seed plants, leaf is the main organ for photosynthesis and production of organic nutrients. The seeds are mobilized to fuel post-germination seedling growth until seedling photosynthesis can be efficiently established. However, the photosynthesis and metabolism in the early growth and development have not been studied systematically and are still largely unknown. In this study, we used two model plants, rice (Oryza sativa L.; monocotyledonous) and Arabidopsis (Arabidopsis thaliana; dicotyledonous) to determine the similarities and differences in photosynthesis in cotyledons and true leaves during the early developmental stages. The photosynthesis-related genes and proteins, and chloroplast functions were determined through RNA-seq, real-time PCR, western blotting and chlorophyll fluorescence analysis. We found that in rice, the photosynthesis established gradually from coleoptile (cpt), incomplete leaf (icl) to first complete leaf (fcl); whereas, in Arabidopsis, photosynthesis well-developed in cotyledon, and the photosynthesis-related genes and proteins expressed comparably in cotyledon (cot), first true leaf (ftl) and second true leaf (stl). Additionally, we attempted to establish an mRNA-lncRNA signature to explore the similarities and differences in photosynthesis establishment between the two species, and found that DEGs, including encoding mRNAs and novel lncRNAs, related to photosynthesis in three stages have considerable differences between rice and Arabidopsis. Further GO and KEGG analysis systematically revealed the similarities and differences of expression styles of photosystem subunits and assembly factors, and starch and sucrose metabolisms between cotyledons and true leaves in the two species. Our results help to elucidate the gene functions of mRNA-lncRNA signatures.

Background: Adverse stress in early life negatively influences psychiatric health by increasing the risk of developing depression and suicide in adulthood. Clinical antidepressants, such as fluoxetine, exhibit unsatisfactory results due to their low efficacy or intolerable side effects. SiNiSan (SNS), a traditional Chinese herbal formula, has been proven to have affirmatory antidepressive effects. However, the underlying mechanism remains poorly understood. Therefore, this study aimed to explore the impact and molecular mechanism of SNS treatment in rats exposed to neonatal maternal separation (MS)-combined young–adult chronic unpredictable mild stress (CUMS). Method: Seventy-two neonatal male Sprague–Dawley rats were randomly divided into six groups of 12 rats each: control + ddH2O, model + ddH2O, positive (fluoxetine: 5 mg/kg), SNS-low dose (2.5 g/kg), SNS-medium dose (5 g/kg), and SNS-high dose (10 g/kg). Behavioral tests included sucrose preference test, open-field test, and forced swimming test. Calcium sensitive receptor (CaSR), protein kinase C (PKC), ERK1/2, and synapse-associated proteins (PSD-95, GAP-43, and synaptophysin [Syn]) in the hippocampus (HIP) and prefrontal cortex (PFC) were assayed using Western blot. CaSR and Syn protein expression was measured by immunohistochemistry. Results: MS-combined CUMS rats exhibited depression-like behavior. SNS exerted antidepressant effects on stress-induced depression-like behavior. The levels of CaSR, PKC, and p-ERK1/2 in the HIP and PFC decreased in stressed rats. SNS treatment significantly upregulated the expression of CaSR, PKC, and p-ERK1/2 in the HIP and PFC of adult stressed rats. Conclusion: MS-combined CUMS could develop depression-like behavior in adult. SNS exhibited antidepressive effects accompanied by improving synaptic plasticity by activation of the CaSR-PKC-ERK signaling pathway.

More than 300 million people suffer from depressive disorders globally. People under early-life stress (ELS) are reportedly vulnerable to depression in their adulthood, and synaptic plasticity can be the molecular mechanism underlying such depression. Herein, we simulated ELS by using a maternal separation (MS) model and evaluated the behavior of Sprague–Dawley (SD) rats in adulthood through behavioral examination, including sucrose preference, forced swimming, and open-field tests. The behavior tests showed that SD rats in the MS group were more susceptible to depression- and anxiety-like behaviors than did the non-MS (NMS) group. Nissl staining analysis indicated a significant reduction in the number of neurons at the prefrontal cortex and hippocampus, including the CA1, CA2, CA3, and DG regions of SD rats in the MS group. Immunohistochemistry results showed that the percentages of synaptophysin-positive area in the prefrontal cortex and hippocampus (including the CA1, CA2, CA3, and DG regions) slice of the MS group significantly decreased compared with those of the NMS group. Western blot analysis was used to assess synaptic-plasticity protein markers, including postsynaptic density 95, synaptophysin, and growth-associated binding protein 43 protein expression in the cortex and hippocampus. Results showed that the expression levels of these three proteins in the MS group were significantly lower than those in the NMS group. LC–MS/MS analysis revealed no significant differences in the peak areas of sex hormones and their metabolites, including estradiol, testosterone, androstenedione, estrone, estriol, and 5β-dihydrotestosterone. Through the application of nontargeted metabolomics to the overall analysis of differential metabolites, pathway-enrichment results showed the importance of arginine and proline metabolism; pantothenate and CoA biosyntheses; glutathione metabolism; and the phenylalanine, tyrosine, and tryptophan biosynthesis pathways. In summary, the MS model caused adult SD rats to be susceptible to depression, which may regulate synaptic plasticity through arginine and proline metabolism; pantothenate and CoA biosyntheses; glutathione metabolism; and phenylalanine, tyrosine, and tryptophan biosyntheses.

Cu+-activated aluminosilicate oxyfluoride glasses were successfully synthesized by melt-quenching method in air by adding Al powder as a reducing agent. Their luminescent properties were studied systematically via optical absorption, excitation, and emission spectra. Upon UV irradiation, a blue-emitting band of Cu+ was observed in glass with relatively low optical basicity. By increasing the optical basicity of glass, obvious redshifts of excitation (290 → 313 nm) and emission (435 → 470 nm) peaks were obtained. Through enhancing Cu+ content, the excitation and emission bands presented further redshifts, which shifted from 313 to 338 nm and 470 to 560 nm, respectively. It is proposed that the absorption band and emitting color of Cu+-doped glass can be tuned by changing the optical basicity of glass and Cu+ concentration. The highest quantum yield can reach 62.5%. More importantly, an investigation of the thermal stability showed that over 85% of the room temperature luminescent intensity is preserved at 200°C. These results imply that Cu+-activated aluminosilicate oxyfluoride glasses may be utilized for UV-converted W-LEDs.

Background: Early adverse life stress is an important dangerous factor in the development of psychiatric disorders, particularly depression. Available clinical antidepressant agents, such as fluoxetine, [a selective serotonin reuptake inhibitor (SSRI)], are unsatisfactory because of their side effects. SiNiSan (SNS) is a classic Chinese medicine prescription regarded to disperse stagnated liver qi to relieve qi stagnation. Therefore, this study was designed to detect the effects and molecular mechanism of SNS treatment in rats subjected to maternal separation (MS).Method: Male neonatal Wistar rats were divided into six groups including control + ddH2O, MS + ddH2O, MS + fluoxetine (5 g/kg), MS + SNS -low dose (2.5 g/kg), MS + SNS -medium dose (5 g/kg), MS + SNS -high dose (10 g/kg). The volume of drugs and ddH2O in each group are according to the weight of rats every day (10 mL/kg). Each group comprised 16 pups with 8 young and 8 adult pups. Except for the control group, all MS groups were separated from their mothers for 4 h/day from 9:00 to 13:00 during postnatal days (PNDs) 1 to 21. After MS, the six groups were intragastrically administered with ddH2O, fluoxetine, and different doses of SNS until PND 28 (for young pups) and PND 56 (for adult pups). The pups were weighed every day, and depression-like behavior was assessed by sucrose preference test, open field test, and forced swimming test. Serotonin 1A (5-HT1A) receptor, phosphorylated protein kinase A (p-PKA) substrate, cAMP response element-binding protein (CREB), p-CREB and brain-derived neurotrophic factor (BDNF) in the hippocampus were examined by Western blot, and in situ 5-HT1A receptor expression was measured by IHC.Results: Young and adult MS rats exhibited depression-like behavior. However, the depression-like behavior was ameliorated by SNS in both age groups. The levels of 5-HT1A receptor, p-CREB, and BDNF in the hippocampus were reduced in young and adult MS rats. SNS treatment significantly up-regulated the expression of 5-HT1A receptor, p-CREB, and BDNF in the hippocampus of adult MS rats. However, few significant effects on the protein expression were observed in the young MS rats.Conclusion: MS in infancy could develop depression-like behavior in young and adult. SNS treatment may perform antidepressant effects on young and adult MS rats through the BDNF/PKA/CREB pathway.

In the present study, we developed and validated a rapid and simple liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of lorlatinib in mouse serum and tissue samples, and such a method was successfully applied to investigate the pharmacokinetic study and tissue distribution of lorlatinib after oral administration. Samples were processed with methanol to precipitate protein and extract drugs, and Afatinib-d6 was used as the internal standard (IS). For LC-MS/MS analysis, compounds were separated on a C18 column by gradient elution (0.1% of formic acid and methanol) at 0.5 mL/min in the positive-ion mode with m/z 407.28 [M + H]+ for lorlatinib and m/z 492.10 [M + H]+ for IS. Good linearity was observed within the calibration ranges. Selectivity, accuracy (−6.42% to 8.84%), precision (1.69% to 10.98%), recoveries (91.4% to 115.0%), and matrix effect (84.2% to 110.6%) were all within the acceptable ranges. After oral administration, serum concentration of lorlatinib quickly achieved the maximal concentration (2,705.683 ± 539.779 μg/L) at 0.625 ± 0.231 h. The highest concentration was detected in the liver (3,153.93 ng/100 mg), followed by the stomach (2,159.92 ng/100 mg) and the kidney (548.83 ng/100 mg). In conclusion, a simple and rapid detection method was established and validated for determination of lorlatinib in blood and tissue samples of mouse. The pharmacokinetic study and tissue distribution of lorlatinib were successfully investigated using this method.

Stress corrosion cracking behavior of 4340 steel in oxygen-containing or chloride containing aqueous solution was researched, the tensile experiment results indicated 100°C deaerated distilled water, the rupture of 4340 steel mainly belongs to ductile fracture, the addition of oxygen or chloride would increase the SCC tendency of 4340 steel and transformed the rupture mechanism from ductile fracture to brittle rupture, the existence of oxygen or chloride would decrease KISCC of 4340 steel in 100°C aqueous solution slightly, the simultaneous action of oxygen and chloride existed, and the simultaneous action would further increase the SCC tendency of 4340 steel in aqueous solution.