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Bupleurum is a kind of medicinal plant that has made a great contribution to human health because of the presence of bioactive metabolites: Bupleurum saikosaponins and flavonoids. Despite their importance, it has been a challenge to visually characterize the spatial distribution of these metabolites in situ within the plant tissue, which is essential for assessing the quality of Bupleurum. The development of a new technology to identify and evaluate the quality of medicinal plants is therefore necessary. Here, the spatial distribution and quality characteristics of metabolites of three Bupleurum species: Bupleurum smithii (BS), Bupleurum marginatum var. stenophyllum (BM), and Bupleurum chinense (BC) were characterized by Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI). Twenty-nine metabolites, including saikosaponins, non-saikosaponins, and compounds from the saikosaponin synthesis pathway, were characterized. Some of these were successfully localized and visualized in the transverse section of roots. In these Bupleurum species, twelve saikosaponins, five non-saikosaponins, and five saikosaponin synthesis pathway compounds were detected. Twenty-two major influencing components, which exhibit higher ion intensities in higher quality samples, were identified as potential quality markers of Bupleurum. The final outcome indicates that BC has superior quality compared to BS and BM. MALDI-MSI has effectively distinguished the quality of these Bupleurum species, providing an intuitive and effective marker for the quality control of medicinal plants.

Objectives: The present study was conducted to explore the performance of micronutrients in the prediction and prevention of coronavirus disease 2019 (COVID-19). Methods: This is an observational case-control study. 149 normal controls (NCs) and 214 COVID-19 patients were included in this study. Fat-soluble and water-soluble vitamins were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis, and inorganic elements were detected by inductively coupled plasma-mass spectrometry (ICP-MS) analysis. A logistic regression model based on six micronutrients were constructed using DxAI platform. Results: Many micronutrients were dysregulated in COVID-19 compared to normal control (NC). 25-Hydroxyvitamin D3 [25(OH)D3], magnesium (Mg), copper (Cu), calcium (Ca) and vitamin B6 (pyridoxic acid, PA) were significantly independent risk factors for COVID-19. The logistic regression model consisted of 25(OH)D3, Mg, Cu, Ca, vitamin B5 (VB5) and PA was developed, and displayed a strong discriminative capability to differentiate COVID-19 patients from NC individuals [area under the receiver operating characteristic curve (AUROC) = 0.901]. In addition, the model had great predictive ability in discriminating mild/normal COVID-19 patients from NC individuals (AUROC = 0.883). Conclusions: Our study showed that micronutrients were associated with COVID-19, and our logistic regression model based on six micronutrients has potential in clinical management of COVID-19, and will be useful for prediction of COVID-19 and screening of high-risk population.

Introduction: Acori Tatarinowii Rhizoma (ATR) is a well-known traditional Chinese medicine that is used for treating neuropathic diseases. However, there is little information about the safety of ATR.Methods: The present study evaluated the acute and subacute oral toxicity of a water extract of ATR in Institute of Cancer Research (ICR) mice. In acute trials, a single administration of extract at a dose 5,000 mg/kg body weight led to no clinical signs of toxicity or mortality, indicating that the lethal dose (LD50) exceeded 5,000 mg/kg. A subacute toxicity test was done using daily doses of 1,250, 2,500, and 5,000 mg/kg of the ATR extract for 28 days, which did not show any adverse clinical symptoms or mortality. However, the male renal organ index and urea level in mice given 5,000 mg/kg was obviously abnormal, which was consistent with pathological results and suggested that this dose might cause kidney injury.Results: Doses of ATR lower than 2,500 mg/kg could be regarded as safe, although the potential cumulative effects of long-term use of high doses of ATR need to be considered.Discussion: The study highlights the function of ATR in reducing blood lipids and provides a new idea for its widespread clinical use in the future.

ObjectiveThis study aims to investigate the relationship between taste dysfunction and depression among patients with schizophrenia, to achieve early detection of depression in clinical practice.MethodsFollowing PRISMA guidance, a comprehensive literature search was conducted globally, covering papers published from 1961 to June 2023. A total of 17 manuscripts were selected through meta-analysis and sensitivity analysis after examining available materials from seven databases to determine the correlation between depression and taste dysfunction.ResultsThe comparison of the 17 selected manuscripts revealed that individuals with gustatory dysfunction may be more likely to experience depressive symptoms (SMD, 0.51, 95% CI, 0.08 to 0.93, p = 0.02). Depression is associated with taste dysfunction in certain aspects, as indicated by the pleasantness ratings of sucrose solutions (SMD, -0.53, 95% confidence interval [CI] -1.11 to 0.05, p = 0.08), gustatory identification ability (SMD, 0.96, 95% CI, 0.03 to 1.89, p = 0.04), and the perception threshold of sweet taste (MD, 0.80, 95% CI, 0.79 to 0.81, p < 0.00001).ConclusionsDue to variations in the methods, designs, and selection criteria employed in the included studies, it is necessary to establish a feasible framework. Future research using detailed and targeted approaches can provide clearer and more unified conclusions on the relationship between taste dysfunction and depression. Moreover, further high-quality research is needed to obtain clearer conclusions and explore the potential of taste dysfunction as an effective tool for early screening of depression.Trial registrationThis review has been registered in the PROSPERO on April 2022 with the identifier CRD42023400172.

This study utilizes China’s records of non-accidental mortality along with twenty-five simulations from the NASA Earth Exchange Global Daily Downscaled Projections to evaluate forthcoming heat stress and heat-related mortality across China across four distinct scenarios (SSP1-2.6, SSP2-4.5, SSP3-7.0, and SSP5-8.5). The findings demonstrate a projected escalation in the heat stress index (HSI) throughout China from 2031 to 2100. The most substantial increments compared to the baseline (1995–2014) are observed under SSP5-8.5, indicating a rise of 7.96°C by the year 2100, while under SSP1-2.6, the increase is relatively modest at 1.54°C. Disparities in HSI growth are evident among different subregions, with South China encountering the most significant elevation, whereas Northwest China exhibits the lowest increment. Projected future temperatures align closely with HSI patterns, while relative humidity is anticipated to decrease across the majority of areas. The study’s projections indicate that China’s heat-related mortality is poised to surpass present levels over the forthcoming decades, spanning a range from 215% to 380% from 2031 to 2100. Notably, higher emission scenarios correspond to heightened heat-related mortality. Additionally, the investigation delves into the respective contributions of humidity and temperature to shifts in heat-related mortality. At present, humidity exerts a greater impact on fluctuations in heat-related mortality within China and its subregions. However, with the projected increase in emissions and global warming, temperature is expected to assume a dominant role in shaping these outcomes. In summary, this study underscores the anticipated escalation of heat stress and heat-related mortality across China in the future. It highlights the imperative of emission reduction as a means to mitigate these risks and underscores the variances in susceptibility to heat stress across different regions.

While it is recognised that the numbers of students needing accessibility supports and accommodations are increasing exponentially, research on accommodations during the COVID-19 pandemic is still sparse. The purpose of the current study was to explore special education teachers’ accommodation practices at secondary schools before and during the unprecedented time of COVID-19. To better understand the experiences of participating teachers, we engaged seven teachers from a prairie province in Canada with one-on-one online semi-structured interviews. Teachers who offered accommodations to students before COVID-19 used a range of accommodations such as general technologies and assistive technology that fall into major categories of accommodations as defined by research. Evidence from this study indicates that some teachers delivered learning packages to homes or taught online classes during school closures, while some teachers did not. Teachers who taught remotely changed some of their accommodation practices during the school closures because in-person classes were switched to online learning. The implications for professional development are also discussed in this paper.

Surface ozone (O3), one of the harmful air pollutants, generated significantly negative effects on human health and plants. Existing O3 datasets with coarse spatiotemporal resolution and limited coverage, and the uncertainties of O3 influential factors seriously restrain related epidemiology and air pollution studies. To tackle above issues, we proposed a novel scheme to estimate daily O3 concentrations on a fine grid scale (1 km × 1 km) from 2018 to 2020 across China based on machine learning methods using hourly observed ground-level pollutant concentrations data, meteorological data, satellite data, and auxiliary data including digital elevation model (DEM), land use data (LUD), normalized difference vegetation index (NDVI), population (POP), and nighttime light images (NTL), and to identify the difference of influential factors of O3 on diverse urbanization and topography conditions. Some findings were achieved. The correlation coefficients (R2) between O3 concentrations and surface net solar radiation (SNSR), boundary layer height (BLH), 2 m temperature (T2M), 10 m v-component (MVW), and NDVI were 0.80, 0.40, 0.35, 0.30, and 0.20, respectively. The random forest (RF) demonstrated the highest validation R2 (0.86) and lowest validation RMSE (13.74 μg/m3) in estimating O3 concentrations, followed by support vector machine (SVM) (R2 = 0.75, RMSE = 18.39 μg/m3), backpropagation neural network (BP) (R2 = 0.74, RMSE = 19.26 μg/m3), and multiple linear regression (MLR) (R2 = 0.52, RMSE = 25.99 μg/m3). Our China High-Resolution O3 Dataset (CHROD) exhibited an acceptable accuracy at different spatial–temporal scales. Additionally, O3 concentrations showed decreasing trend and represented obviously spatiotemporal heterogeneity across China from 2018 to 2020. Overall, O3 was mainly affected by human activities in higher urbanization regions, while O3 was mainly controlled by meteorological factors, vegetation coverage, and elevation in lower urbanization regions. The scheme of this study is useful and valuable in understanding the mechanism of O3 formation and improving the quality of the O3 dataset.

Abstract As the unique rotating component, the impeller is the core component of a nuclear reactor coolant pump (RCP), the dynamic properties of the impeller are critical for the safe operation of the whole reactor. The purpose of this study was to shed comprehensive light on the pressure pulsation and modal properties of a scaled RCP impeller via experimental and numerical methods. The numerical model was validated by an experiment connecting the pressure pulsation signals at the diffuser inlet, and a good agreement was obtained between the numerical and experimental results. Pressure pulsation acting on the impeller's blade is mainly dominated by the impeller rotating frequency, the vane passing frequency, and the double blade‐passing frequency, and the pressure pulsation acting on the blade's pressure surface is more intense than on the suction surface. The modal properties were obtained via the modal test and numerical methods with the impeller suspended as a free body in the air and submerged inside water. The reduction in the impeller natural frequencies was between 31.63% and 37.77% for the corresponding mode shape due to the added mass effect of the fluid. Based on the pressure pulsation characteristics acting on the impeller and the natural frequency of the impeller, it is considered there is no risk of resonance in the impeller. Finally, it is expected that the present work can provide scientific guidance to avoid hydraulic resonance in nuclear reactor coolant pumps.

The nuclear reactor coolant pump transferring heat energy inherently brings with it the unsteady flow and inevitably threatens to the safe operation of the pump unit, especially with the pressure pulsation induced by the rotor-stator interaction. In this paper, the characteristics of pressure pulsation of the diffuser in a nuclear reactor coolant pump were investigated by the numerical simulation with experimental validation. Pressure pulsation signals measured synchronously from sensors mounted on the radial diffuser of a model pump were analyzed via Welch’s method. Frequency components induced by the rotor-stator interaction can be revealed by the diameter mode analysis method. The pressure pulsation of the diffuser is dominated by the blade passing frequency and its harmonics, which are free from the effect of flow rate and rotational speed while the corresponding amplitudes are easily affected by different operational conditions and measuring positions. The non-uniformity is much more affected by the rotational speed than the flow rate. This research is helpful for further work to reduce the pressure pulsation for the reactor coolant pump.

Hyperkalemia is a critical condition requiring careful evaluation and timely intervention. Many conditions could manifest as pseudohyperkalemia and it's important to differentiate them as inappropriate potassium-lowering therapy might lead to detrimental outcomes. A 56-year-old female was admitted for hyperkalemia (5.62–8.55 mmol/L). She had no symptoms or signs of hyperkalemia. A comprehensive work-up of hyperkalemia retrieved no valuable findings. Her blood samples underwent incubation tests at different temperatures and revealed temperature-dependent potassium leaks from red blood cells. Based on all test results, a diagnosis of hyperkalemia caused by red blood cell membrane defects was suspected. Whole-genome sequencing revealed a heterozygous c.1123C>T (p. R375W) mutation in the ABCB6 gene and confirmed the diagnosis of familial pseudohyperkalemia (FP). FP is an inherited benign condition in which red blood cells have increased cold-induced permeability to potassium. The patient was discharged with no additional treatment and she was suggested avoiding blood donation.

Acute vascular injury provokes an inflammatory response, resulting in neointimal hyperplasia (NIH) and downstream pathologies. The resolution of inflammation is an active process in which specialized proresolving lipid mediators (SPM) and their receptors play a central role. We sought to examine the acute phase response of SPM and their receptors in both circulating blood and the arterial wall in a rat angioplasty model. We found that the ratio of proresolving to pro-inflammatory lipid mediators (LM) in plasma decreased sharply 1 day after vascular injury, then increased slightly by day 7, while that in arteries remained depressed. Granulocyte expression of SPM receptors ALX/FPR2 and DRV2/GPR18, and a leukotriene B4 receptor BLT1 increased postinjury, while ERV1/ChemR23 expression was reduced early and then recovered by day 7. Importantly, we show unique arterial expression patterns of SPM receptors in the acute setting, with generally low levels through day 7 that contrasted sharply with that of the pro-inflammatory CCR2 receptor. Overall, these data document acute, time-dependent changes of LM biosynthesis and SPM receptor expression in plasma, leukocytes, and artery walls following acute vascular injury. A biochemical imbalance between inflammation and resolution LM pathways appears persistent 7 days after angioplasty in this model. These findings may help guide therapeutic approaches to accelerate vascular healing and improve the outcomes of vascular interventions for patients with advanced atherosclerosis.

Objective This study offers meta-analytic data on the potential association between epilepsy and depression especially for the prevalence of depression in epilepsy or vice versa. Methods The relevant studies were searched and identified from nine electronic databases. Studies that mentioned the prevalence and/or incidence of epilepsy and depression were included. Hand searches were also included. The search language was English and the search time was through May 2022. Where feasible, random-effects models were used to generate pooled estimates. Results After screening electronic databases and other resources, 48 studies from 6,234 citations were included in this meta-analysis. The period prevalence of epilepsy ranged from 1% to 6% in patients with depression. In population-based settings, the pooled period prevalence of depression in patients with epilepsy was 27% (95% CI, 23–31) and 34% in clinical settings (95% CI, 30–39). Twenty studies reported that seizure frequency, low income, unemployment of the patients, perception of stigma, anxiety, being female, unmarried status, disease course, worse quality of life, higher disability scores, and focal-impaired awareness seizures were risk factors for depression. Conclusion Our study found that epilepsy was associated with an increased risk of depression. Depression was associated with the severity of epilepsy.

Metabolic syndrome (MetS) is an independent risk factor for hepatocellular cancer (HCC). Currently, there is no highly sensitive and specific biomarkers for HCC surveillance in MetS population. Metabolomics has been reported as a powerful technology for biomarker discovery. In the present study, we aimed to explore novel biomarkers with high sensitivity and specificity for MetS-positive [MetS(+)] HCC by metabolomic analysis. At first, many serum metabolites were found dysregulated in MetS(+) HCC individuals. Validation of the dysregulated metabolites by targeted metabolite analyses revealed that serum L-glutamic acid (L-glu), pipecolic acid (PA) and 7-methylguanine (7-mG) were increased in MetS(+) HCC compared to MetS group. Then a biomarker panel including L-glu, PA and alpha-fetoprotein (AFP) was identified as a novel biomarker for the diagnosis of MetS(+) HCC. Receiver operating characteristic (ROC) curve was drawn and the area under the ROC curve (AUC) was 0.87 for discriminating MetS(+) HCC from MetS group. The biomarker panel was capable of detecting small (AUC = 0.82) and early-stage (AUC = 0.78) tumors as well. Moreover, it exhibited great diagnostic performance (AUC = 0.93) for discriminating MetS(+) HCC from other MetS-associated cancers, including colorectal cancer and gastric cancer. Collectively, our study establishes a novel diagnostic tool for MetS(+) HCC.

Due to Indonesia’s geographical location within the Pacific Ring of Fire, it is susceptible to earthquake occurrences. Therefore, the implementation of an Earthquake Early Warning (EEW) System is crucial to mitigate the impact of earthquakes. This study focused on deploying an on-site EEW system on Bali Island, an Indonesian region known for its elevated seismic activity. The study evaluated the system’s performance over five months in 2023. Throughout this observation period, the AI-based on-site EEW system successfully detected the earthquake’s P-wave before the occurrence of stronger seismic waves, such as the peak ground acceleration (PGA). It provided a warning time of up to 75 seconds and accurately predicted the intensity of the impending earthquake. These outcomes meet the fundamental requirements for an effective EEW system. The results obtained from the deployed AI-based on-site EEW system demonstrate the potential for wider implementation of such systems across Indonesia.

Type 2 diabetes mellitus (T2DM) has been recognized as one of the most important and independent risk factors for hepatocellular cancer (HCC). However, there is still a lack of ideal tumor markers for HCC detection in the T2DM population. Serum lipids have been revealed as potential tumor markers for HCC. In this study, our objective was to develop a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to detect several lipids including 8,15-dihydroxy-5,9,11,13-eicosatetraenoic acid (8,15-DiHETE), hexadecanedioic acid (HDA), 15-keto-13,14-dihydroprostaglandin A2 (DHK-PGA2), ricinoleic acid (RCL), octadecanedioic acid (OA) and 16-hydroxy hexadecanoic acid (16OHHA) in serum and explore their diagnostic potential for T2DM-positive [T2DM(+)] HCC. A robust LC-MS/MS method was established for the measurement of 8,15-DiHETE, HDA, DHK-PGA2, RCL, OA, and 16OHHA. The methodology validation was conducted, and the results suggested the reliability of this LC-MS/MS method for targeted lipids. Several serum lipids, including 8,15-DiHETE, HDA, DHK-PGA2, and OA were increased in T2DM(+) HCC patients. A biomarker signature that incorporated HDA, DHK-PGA2, and AFP was established and showed good diagnostic potential for T2DM(+) HCC, and the area under the ROC curve (AUC) was 0.87 for diagnosing T2DM(+) HCC from T2DM individuals. Additionally, the biomarker signature diagnosed small-size (AUC = 0.88) and early-stage (AUC = 0.79) tumors with high efficacy. Moreover, the biomarker signature could differentiate T2DM(+) HCC from other T2DM(+) tumors, including pancreatic, gastric and colorectal cancer (AUC = 0.88) as well. In conclusion, our study develops a novel tool for early diagnosis of T2DM(+) HCC in T2DM patients.

Hepatitis B virus (HBV)-derived hepatocellular cancer (HCC) is a serious threat to human health, especially in China. There is no highly sensitive and specific HCC biomarker at present, which makes it difficult to detect HCC at the early stage. Serum exosomal circular RNAs (circRNAs) have been reported as novel diagnostic and prognostic biomarkers of cancers. In the present study, we aimed to explore the diagnostic performance of serum exosomal circRNAs for HBV-derived HCC screening. At first, many circRNAs were found to be differentially expressed in the serum exosomes of HCC individuals by microarray analysis. The validation of dysregulated circRNAs by qRT-PCR revealed that serum exosomal hsa_circ_0028861 was decreased in HCC compared to chronic HBV and cirrhosis. Then, hsa_circ_0028861 was identified as a novel biomarker for HCC diagnosis with an area under the ROC curve (AUC) of 0.79 for discriminating HCC from chronic HBV and cirrhosis individuals. Hsa_circ_0028861 was capable of detecting small (AUC = 0.81), early-stage (AUC = 0.82) and AFP-negative [AFP (−)] (AUC = 0.78) tumors as well. The combination of hsa_circ_0028861 and AFP exhibited better diagnostic ability (AUC = 0.86 for discriminating HCC from chronic HBV and cirrhosis). Moreover, bioinformatics prediction suggested that hsa_circ_0028861 might influence HCC progression by regulating its targeted microRNAs (miRNAs) and downstream tumor-related signaling pathways. Collectively, our study reveals a novel diagnostic tool for HBV-derived HCC.

Type 2 diabetes mellitus (T2DM) has been identified as an independent risk factor for hepatocellular cancer (HCC). However, there are no ideal biomarkers for the surveillance and early detection of HCC in the T2DM population at present. In this study, we aimed to explore novel metabolite biomarkers for T2DM-positive [T2DM(+)] HCC by metabolomic analysis. At first, many serum metabolites were found dysregulated in T2DM(+) HCC patients in untargeted metabolomic analyses. Targeted metabolite analyses confirmed that serum benzoic acid and citrulline were increased, and creatine was decreased in T2DM(+) HCC compared to the T2DM group. A metabolite classifier including benzoic acid, creatine, and citrulline was identified as a novel biomarker for the diagnosis of T2DM(+) HCC, with an area under the ROC curve (AUC) of 0.93 for discriminating T2DM(+) HCC patients from T2DM patients. In addition, the metabolite classifier detected small-size (AUC = 0.94), early-stage (AUC = 0.94), and AFP-negative (AUC = 0.96) tumors with high sensitivity and specificity. The combination of this metabolite classifier and AFP might be useful in the surveillance and early detection of HCC in the T2DM population. In conclusion, this study establishes a novel diagnostic tool for T2DM(+) HCC.

Atmospheric pressure hydrolysis without stirring and a combustion–calcination method were utilized to fabricate magnetic Fe _3 O _4 / α -Fe _2 O _3 heterogeneous nanorods. First, the β -FeOOH nanorods were fabricated via hydrolysis, and the concentration of Fe ^3+ , hydrolysis temperature, and hydrolysis time were optimized. The optimal fabrication conditions were as follows: a 0.1 M FeCl _3 solution was hydrolyzed at 90 °C for 2 h. The average length and diameter of the β -FeOOH nanorods fabricated under the optimal conditions were approximately 216 and 58 nm, respectively. Subsequently, Fe _3 O _4 / α -Fe _2 O _3 heterogeneous nanorods were fabricated via a combustion–calcination process. The volume of absolute ethanol, calcination temperature, and calcination time were investigated to optimize the fabrication conditions of Fe _3 O _4 / α -Fe _2 O _3 heterogeneous nanorods under the following conditions: absolute ethanol: 50 ml; calcination temperature: 300 °C; and calcination time: 2 h. Magnetic Fe _3 O _4 / α -Fe _2 O _3 heterogeneous nanorods fabricated under optimal conditions were characterized with an average length of 199 nm, an average diameter of 51 nm, a zeta potential of +17.2 mV, and a saturation magnetization of 13 emu·g ^–1 .

A systematic study of the phase composition and element occurrence characteristics of tellurides in tellurium-bearing gold deposits will be helpful for the genesis understanding of gold deposits of this type and for prospecting exploration. Tellurides in the Jinqingding gold deposit are too small and are difficult to identify. Previous research lacked the detailed studies of the element distribution characteristics of tellurides. In this study, the types, symbiotic relationship, chemical composition and element distribution characteristics of tellurides in the deposit were analyzed by electron probe using BSE, WDS, EDS and mapping modes. Results show that petzite is closely associated with hessite and intergrowths of these two minerals are common. Au and Ag are unevenly distributed in the intergrowths, and calaverite shows as a bright spot in the scanning map. Tellurium is always likely to combine with Ag to form hessite. With the consumption of Ag, petzite began to appear and Te combined with Au to form calaverite after exhausting Ag in magmatic hydrothermal fluids. The superfluous Au in the hydrothermal fluids at the later stage of mineralization reacted with hessite or petzit to produce unconventional tellurides, finally forming a native gold. The growth of gold-silver minerals follows the sequence, hessite, petzite, calaverite, and Au from early to late. This study provides technical support for the comprehensive utilization of tellurium-bearing gold deposits.

Background: Depression is a common disease that endangers people’s physical and mental health. Traditional Chinese medicine has advantages in treating the emotional and cognitive symptoms of depressive disorders. Objective: To study the effects of baicalin on the behavior and to clarify the underlying mechanism through evaluation of the Rac1-LIMK1-cofilin pathway. Methods: A chronic mild stress (CMS) model of depression was used. Baicalin was administered to the mice for the intervention, and the positive control group was treated with fluoxetine. Behavioral tests were conducted to observe the degree of depressive disorders. Synaptophysin (SYP), postsynaptic density protein-95 (PSD95), brain-derived neurotrophic factor (BDNF), tyrosine kinase receptors (TrkB), Rac1 and cofilin expression was determined using Western blot analysis, and mRNA was quantified using real-time PCR. Results: Mice in the CMS group showed an increase in depression-like behavior (p 0.05). Conclusion: Baicalin markedly alleviated depression-like behavioral changes, exerted effects on SYP, PSD95, BDNF, and TrkB expression, activated the Rac1-cofilin pathway, and subsequently improve synaptic plasticity.

During LA-ICP-MS analysis, the key factor influencing data accuracy of sample analysis is whether the sample can be uniformly delivered from the laser sample chamber to the torch of the ICP-MS.An external container between LA and ICP-MS and a multi-channel rotary sampling cell, which can effectively eliminate the sample position effect during the laser ablation was designed for the study reported in this paper.The pattern of aerosol delivered to ICP-MS is approximately continuous and at the same time, this can greatly improve the stability.Under optimal conditions, using 91500 as external standard, the standard zircons GJ-1, Ple ovice, TEMROA and QH yield U-Pb ages of 604±3 Ma(2δ, MSWD=1.2), 337±1 Ma(2δ, MSWD=1.18), 419±3 Ma(2δ, MSWD=0.15) and 161±1 Ma(2δ, MSWD=0.6), respectively, which agree well with the previously reported ID-TIMS and SHRIMP ages.For the same conditions, using NIST610 as external standard, most trace element results of the glass standards NIST612 and BHVO-2G fall within 10% range of the reference values.The 207Pb/206Pb weighted mean age of zircons from the Tianshan Orogen of Xinjiang is consistent with the previous SHRIMP U-Pb age within uncertainty.This method can effectively reduce the elemental fractionation effects and improve the reliability of the analytical data.

Beijing Haze has been phenomenal, especially for winter, and widely considered a result of the increasing anthropogenic emissions of atmospheric pollutants in the region. Since 2013, the pollutant emissions have been reduced with the help of a series of emission-control actions. However, severe haze events still occurred frequently in Beijing in recent winters, e.g., those of 2015 and 2016, implying that other factors such as meteorological conditions and interannual climate variability have also played an important role in forming the haze. Based on homogenized station observations, atmospheric circulation reanalysis and anthropogenic emissions data for the period 1980–2017, this paper attempts to quantify the relative importance of anthropogenic emissions and climatic conditions to the frequency and intensity of Beijing Haze in winter. It is found that the frequency (number) of hazy days exhibits large interannual variability and little trend, and its variations were mainly controlled by climate variability, with a correlation coefficient of 0.77. On the other hand, the intensity of haze displays strong interannual variability and a significant increasing trend during 1980–2012 and a notable decreasing trend during 2012–2017. The multiple linear regression model suggests that about half of the total variance of the haze intensity is explained by climate variability (mainly for interannual variations), and another half by the changing emissions (mainly for the trends).

Salmonella typhimurium is a highly transmissible pathogen in rabbits that causes significant losses. Danofloxacin shows excellent efficacy against S. typhimurium infections. However, there are few reports of the pharmacokinetic/pharmacodynamic (PK/PD) modeling of danofloxacin against this pathogen. The aim of this study was to evaluate the in vivo PK/PD relationship of danofloxacin in rabbits infected with S. typhimurium. We used the reduction of bacterial burden in the blood, liver, spleen, and lung as the target PD endpoints, and determined the PK/PD indexes that best correlated with the efficacy and its corresponding magnitude. Danofloxacin was administrated orally to experimentally S. typhimurium-infected rabbits once daily for three successive days. The concentrations of danofloxacin in the serum and the bacterial burden in the blood, liver, spleen, and lung were determined. The PK/PD relationships of danofloxacin against S. typhimurium were evaluated using a Sigmoid Emax model. The results showed that the area under the concentration-time curve from 0 to 24 h/minimum inhibitory concentration (AUC24 h/MIC) ratio correlated well with the in vivo antibacterial effectiveness in different organs, with an r2 of 0.8971, 0.9186, 0.9581, and 0.8708 in the blood, liver, spleen, and lung, respectively. The AUC24 h/MIC ratios for the bactericidal effect (3 × Log10 colony forming units/mL reductions) were 121.30, 354.28, 216.64, and 228.66 in the blood, liver, spleen, and lung, respectively, indicating that the in vivo effectiveness of danofloxacin against S. typhimurium using bacterial reduction in different organs as PD endpoints was not identical. This study illustrated that the selection of the target organ for bacterial reduction determination had little effect on best PK/PD parameter determination, but is critical for parameter magnitude calculation in antimicrobial PK/PD modeling, and furthermore, has an impact on the rational dosage optimization process.