A Rapid, Sensitive, and High-throughput Method for the Simultaneous Determination of Antihypertensive Drug Combinations in Dog Plasma by UHPLC-MS/MS: The Assessment of Predicable Bioequivalence of In-vitro Dissolution Condition.

BACKGROUND: Essential hypertension is a common clinical disease and a risk factor for cardiovascular and cerebrovascular diseases. Olmesartan medoxomil, amlodipine, and hydrochlorothiazide are commonly used antihypertensive drugs. The aim of this study was to establish a robust UPLC-MS/MS method for the simultaneous determination of olmesartan medoxomil, amlodipine, and hydrochlorothiazide in dog plasma. At the same time, the release in vivo and in vitro studies were conducted, and a preliminary in vitro-in vivo correlation (IVIVC) evaluation was performed. METHODS: The bioequivalence experiment was conducted with a double-crossed design. Three major components were extracted and analyzed by UHPLC-MS/MS. With the MRM scan, olmesartan and amlodipine were quantified by fragment conversion (m/z 447.10→190.10) and (m/z 408.95→294.00) under positive ESI mode, while hydrochlorothiazide was quantified with fragment conversion (m/z 295.90→268.90) under negative ESI mode. The in vitro release studies were performed using a USP paddle, and the dissolution medium was chosen from pH 6.0 to pH 6.8 according to the BCS classification of compounds. The IVIVC was calculated using the Wagner-Nelson equation. RESULTS: The linear ranges of olmesartan, amlodipine, and hydrochlorothiazide in the plasma were 5.0-2500, 0.1-50, and 3.0-1500 ng/mL, respectively. All accuracies were within 3.8% of the target values, and the findings revealed that intra-day and inter-day accuracy was less than 12.1%. Moreover, the recoveries exceeded 88.3%, the matrix effect tests were positive, and the stability tests were positive. With the establishment of correlation, the distinguishable dissolution condition (pH 6.8) was selected as the predictable condition. CONCLUSION: The established method was suitable for the preclinical pharmacokinetic study of tripartite drugs with strong specificity and high sensitivity. Through the evaluation of IVIVC, the connection between in vivo and in vitro drug testing was initially established.

Diagnosis and Vulnerability Risk Assessment of Atherosclerotic Plaques Using an Amino Acid-Assembled Near-Infrared Ratiometric Nanoprobe.

To reduce the risk of atherosclerotic disease, it is necessary to not only diagnose the presence of atherosclerotic plaques but also assess the vulnerability risk of plaques. Accurate detection of the reactive oxygen species (ROS) level at plaque sites represents a reliable way to assess the plaque vulnerability. Herein, through a simple one-pot reaction, two near-infrared (NIR) fluorescent dyes, one is ROS responsive and the other is inert to ROS, are coassembled in an amphiphilic amino acid-assembled nanoparticle. In the prepared NIR fluorescent amino acid nanoparticle (named FANP), the fluorescent properties and ROS-responsive behaviors of the two fluorescent dyes are well maintained. Surface camouflage through red blood cell membrane (RBCM) encapsulation endows the finally obtained FANP@RBCM nanoprobe with not only further reduced cytotoxicity and improved biocompatibility but also increased immune escape capability, prolonged blood circulation time, and thus enhanced accumulation at atherosclerotic plaque sites. In vitro and in vivo experiments demonstrate that FANP@RBCM not only works well in probing the occurrence of atherosclerotic plaques but also enables plaque vulnerability assessment through the accurate detection of the ROS level at plaque sites in a reliable ratiometric mode, thereby holding great promise as a versatile tool for the diagnosis and risk assessment of atherosclerotic disease.

Assessment of the sacroiliac joint in patients with axial spondyloarthritis via three-dimensional ultrashort echo time magnetic resonance imaging.

Background: Bone erosion in the sacroiliac joint (SIJ) is highly specific for the diagnosis of axial spondyloarthritis (axSpA) and may indicate early disease progression. The 3D ultrashort echo time (3D-UTE) technique excels in providing clear contrast between the articular cartilage and the bone cortex interface. Additionally, it is emerging as a promising quantitative tool for detecting early cartilage changes. Therefore, this study aimed to evaluate the diagnostic performance of 3D-UTE sequences in identifying bone erosion in the SIJ of patients with axSpA and to clarify the potential of cartilage T2* values as a quantitative biomarker for axSpA. Methods: This prospective study employed convenience and consecutive sampling methods to recruit patients diagnosed with axSpA in Peking University Third Hospital who met the Assessment of Spondyloarthritis International Society (ASAS) criteria and also an equal number of healthy volunteers. After providing informed consent, all participants underwent 3D-UTE sequences and conventional T2* mapping of the SIJs. Two radiologists separately interpreted the bone erosion of each SIJ on 3D-UTE sequences. Erosion detection of SIJs via computed tomography (CT) served as the standard of reference. The T2* values of the cartilage were measured and compared, and the diagnostic efficacy of the T2* value for axSpA diagnosis was evaluated. Results: A total of 32 patients and 32 healthy volunteers were included. The 3D-UTE sequence, as separately assessed by two reviewers in terms of its ability to detect erosions, exhibited a notable level of accuracy. For the two reviewers, the respective diagnostic sensitivities were 94.7% and 92.9%, the specificities were 97.4% and 96.5%, positive predictive values were 96.7% and 95.4%, the negative predictive values were 95.9% and 94.5%, the accuracies were 96.2% and 94.9%, and the areas under the curve (AUCs) were 96.1% and 94.7%. For the detection of erosions, the interreader κ value was 0.949. The T2* values of the SIJ cartilage were significantly higher in patients with axSpA than in healthy volunteers. The intraobserver intraclass correlation coefficients (ICCs) for T2* measurements ranged between 80.5% and 82.2%. Meanwhile, the interobserver ICCs for UTE-T2* and gradient echo T2* measurements were 81.5% and 80.8%, respectively. The AUCs of the UTE-T2* values for discriminating patients with axSpA from the healthy volunteers of the two readers were 73.3% and 71.6%, respectively. Conclusions: 3D-UTE sequences can be used as a reliable morphological imaging technique for detecting bone erosion in the SIJ. Additionally, UTE-T2* values of the cartilage may offer a quantitative method for identifying patients with axSpA.

Toxicity assessment of dioxins and their transformation by-products from inferred degradation pathways.

Due to the significant POPs characteristics, dioxins caused concern in public health and environmental protection. Evaluating the toxicity risk of dioxin degradation pathways is critical. OCDD, 1,2,3,4,6,7,8-HpCDD, and 1,2,3,4,6,7,8-HpCDF, which are highly abundant in the environment and have strong biodegradation capabilities, were selected as precursor molecules in this study. Firstly, their transformation pathways were deduced during the metabolism of biometabolism, microbial aerobic, microbial anaerobic, and photodegradation pathways, and density function theory (DFT) was used to calculate the Gibbs free energy to infer the possibility of the occurrence of the transformation pathway. Secondly, the carcinogenic potential of the precursors and their degradation products was evaluated using the TOPKAT modeling method. With the help of the positive indicator (0-1) normalization method and heat map analysis, a significant increase in the toxic effect of some of the transformation products was found, and it was inferred that it was related to the structure of the transformation products. Meanwhile, the strength of the endocrine disrupting effect of dioxin transformation products was quantitatively assessed using molecular docking and subjective assignment methods, and it was found that dioxin transformation products with a higher content of chlorine atoms and molecules similar to those of thyroid hormones exhibited a higher risk of endocrine disruption. Finally, the environmental health risks caused by each degradation pathway were comprehensively assessed with the help of the negative indicator (1-2) standardization method, which provides a theoretical basis for avoiding the toxicity risks caused by dioxin degradation transformation. In addition, the 3D-QSAR model was used to verify the necessity and rationality of this study. This paper provides theoretical support and reference significance for the toxicity assessment of dioxin degradation by-products from inferred degradation pathways.

Preoperative assessment of fistula-in-ano using SonoVue enhancement during three-dimensional transperineal ultrasound.

Background: Accurate preoperative evaluation of fistula-in-ano can guide the choice of surgical procedure and may improve healing rates. This prospective study aimed to evaluate the accuracy of conventional 3D transperineal ultrasound (3D-TPUS) compared with SonoVue (SVE)-enhanced 3D-TPUS for the detection and classification of anal fistula. Methods: In this prospective study, 3D-TPUS reconstructions were performed before and after SVE enhancement in 60 patients with fistula-in-ano who intended to undergo surgery at the Department of Anorectal Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University (P. R. China) between January 2021 and October 2021. Accuracies of anal fistula classification, complexity classification, detection of anal fistula branches, and detection of internal opening between 3D-TPUS and SVE 3D-TPUS were compared based on a reference standard-intraoperative findings. Results: This study enrolled 60 patients (mean age, 37.1 ± 11.4 years; mean follow-up, 9 ± 3 months). Intraoperative findings showed that the fistula type was intersphincteric in 23 patients (38.3%), trans-sphincteric in 35 (58.3%; 12 high and 23 low), and suprasphincteric in 2 (3.3%). Moreover, 68 internal openings were found. Compared with the accuracy of 3D-TPUS, that of SVE 3D-TPUS was similar in fistula classification [95.0% (57/60) vs 96.7% (58/60), P = 0.392], but significantly higher in internal opening evaluation [80.9% (55/68) vs 97.1% (66/68), P = 0.001], complexity classification [85.0% (51/60) vs 98.3% (59/60), P = 0.018], and detection of fistula branches [70.4% (19/27) vs 92.6% (25/27), P = 0.031]. Conclusions: SVE 3D-TPUS may be a useful examination for patients with perianal fistulae because of its high accuracy and consistency with intraoperative findings, especially in complex fistula-in-ano and difficult cases.

Mental Telehealth Utilization Patterns Among High School Students from Racial and Ethnic Minority Backgrounds Affected by Violence and Substance Use.

BACKGROUND: Recent data show high school students from racial and ethnic minority (REM) backgrounds in the United States confront a twofold challenge, marked by the highest rates of firearm-related homicides since 1994 and increased youth substance use. The pandemic increased online and telehealth usage opportunities for at-risk REM youth. Therefore, this study investigated (1) the frequency and prevalence of co-occurring youth violence and substance use among REM adolescents, (2) racial/ethnic, age, and natal sex (as gender data was not collected) differences in patterns and trends in co-occurring youth violence and substance use among REM adolescents, and (3) the relationship between these syndemic issues and REM adolescent mental telehealth use during the pandemic. METHODS: Data was sourced from a nationally representative sample of U.S. 9th-12th students (n = 3241) who completed the CDC's 2021 Adolescent and Behavioral Experiences Survey (ABES). Using univariate (frequency distribution), bivariate (Pearson's chi-squared test), and multivariate logistic regression models, we examined seven violence victimization outcomes, four violence perpetration outcomes, two family violence outcomes, and six substance use outcomes and their associations with telehealth use for mental health (dependent variable) among REM adolescents. RESULTS: This sample was primarily female (50.7%), Black or African American (48.3%), Hispanic or Latinx (20.6%), and identified as straight or heterosexual (69.5%). The study found significant sex-based differences in violence perpetration/victimization, substance use, and telehealth use for mental health. In general, mental telehealth use was significantly associated with substance use among REM adolescents (cigarette smoking, vaping, alcohol, marijuana, prescription meds, and illicit drug use) (p-value = .001). Mental telehealth use was also significantly associated with all peer and family violence outcomes (p < 0.001). Controlling for covariates, gun carrying was associated with 4.8 times higher odds of using mental telehealth. Students in a physical fight or carrying a weapon (gun, knife, or club) on school property had 2.45 times and 8.09 times the odds of utilizing mental telehealth. Bullied students were 2.5 times more likely to use mental telehealth (p-value < 0.05). Illicit drug use (cocaine, heroin, methamphetamines, and ecstasy) was associated with a higher likelihood of mental telehealth use (AOR = 1.3, p-value = .05). CONCLUSION: Our results suggest crucial insights for shaping violence and substance use prevention strategies, with implications for the future of online and telehealth behavioral services. Mental telehealth help-seeking emerges as a crucial avenue for supporting adolescents affected by violence and substance use, especially when they face obstacles to accessing traditional services. It can work in tandem with in-person services to address these challenges.

COVID-19 pandemic impact on the potential exacerbation of screening mammography disparities: A population-based study in Ontario, Canada.

Strategies to ramp up breast cancer screening after COVID-19 require data on the influence of the pandemic on groups of women with historically low screening uptake. Using data from Ontario, Canada, our objectives were to 1) quantify the overall pandemic impact on weekly bilateral screening mammography rates (per 100,000) of average-risk women aged 50-74 and 2) examine if COVID-19 has shifted any mammography inequalities according to age, immigration status, rurality, and access to material resources. Using a segmented negative binomial regression model, we estimated the mean change in rate at the start of the pandemic (the week of March 15, 2020) and changes in weekly trend of rates during the pandemic period (March 15-December 26, 2020) compared to the pre-pandemic period (January 3, 2016-March 14, 2020) for all women and for each subgroup. A 3-way interaction term (COVID-19*week*subgroup variable) was added to the model to detect any pandemic impact on screening disparities. Of the 3,481,283 mammograms, 8.6 % (n = 300,064) occurred during the pandemic period. Overall, the mean weekly rate dropped by 93.4 % (95 % CI 91.7 % - 94.8 %) at the beginning of COVID-19, followed by a weekly increase of 8.4 % (95 % CI 7.4 % - 9.4 %) until December 26, 2020. The pandemic did not shift any disparities (all interactions p > 0.05) and that women who were under 60 or over 70, immigrants, or with a limited access to material resources had persistently low screening rate in both periods. Interventions should proactively target these underserved populations with the goals of reducing advanced-stage breast cancer presentations and mortality.

Research on the dynamic changes of China's agro-processing industry agglomeration and spatial impact of production factors on agglomeration.

Agglomeration is an important phenomenon that accompanies with a large concentration of various production factors. Since the agro-processing industry has become a vital bridge connecting the primary and secondary industries, agglomeration and distribution within this industry are arousing wide concern. Based on provincial panel data of China from 2001 to 2020, this study described the dynamic changes of China's agro-processing industry agglomeration using spatial Gini coefficient and average concentration ratio. A theoretical analysis framework was established and a dynamic spatial Durbin model was used to quantitatively explore the spatial effects of production factors on the agro-processing industry agglomeration, results showed that: first, the agglomerations of agro-processing industry and its sub-industries all have exhibited a fluctuating trend of "up-down-up-down", meanwhile the agro-processing industry shifted from the Eastern coastal region to the central and western regions. Second, in the short term, the capital, labor, and technology factors respectively have remarkably promoted the agro-processing industries agglomeration both in local and neighboring areas. Third, in the long term, these three production factors all had a crowding effect on industrial agglomeration. Therefore, it is necessary to continue optimizing the agro-processing industry spatial layout through adjusting production factor inputs to promote high-quality development of the agro-processing industry.

Pyrrolizidine Alkaloids in Tea (Camellia sinensis L.) from Weeds through Weed-Soil-Tea Transfer and Risk Assessment of Tea Intake.

Pyrrolizidine alkaloids (PAs) have been detected in tea and can threaten human health. However, the specific source of PAs in tea is still unclear. Here, 88 dried tea products collected from six major tea-producing areas in Anhui Province, China, were analyzed. The detection frequency was 76%. The content of total PAs in dried tea was between 1.1 and 90.5 µg/kg, which was all below the MRL recommended by the European Union (150 µg/kg). In the Shexian tea garden, PAs in the weeds and weed rhizospheric soil around tea plants and the fresh tea leaves were analyzed. Intermedine (Im), intermedine-N-oxide (ImNO), and jacobine-N-oxide (JbNO) were transferred through the weed-to-soil-to-tea route into the fresh tea leaves; only Im and ImNO were detected in dried tea samples. Potential risk of the total PAs in the tea infusion was assessed according to the margin of exposure method, and it might be a low concern for public health.

[Potential Source Identification and Ecological Risk Assessment of Heavy Metals in Surface Soil of Heze Oil Peony Planting Area Based on PMF-PCA/APCS and PERI].

To study the sources and potential risks of heavy metals in soils of characteristic agricultural product producing areas is of great significance for the scientific management and safe utilization of soil and crop resources. The contents of heavy metals As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn in the 254 surface soil samples collected from the Heze oil peony planting area were determined. The content characteristics and correlation of heavy metals were analyzed using multivariate statistical methods. The sources of heavy metals in topsoil were analyzed using Igeo, PMF, and PCA/APCS. The ecological risks of the eight heavy metals were assessed through the potential ecological risk index (PERI). The results showed that the average contents of seven heavy metals in the soil were basically consistent with the background values of soil elements in Heze City, except that the average value of Cd was 1.44 times higher than the background value in Heze City. Correlation analysis and cluster analysis revealed that Pb, Hg, and Cd elements in the soil were greatly affected by human activities in the later period. The sources of eight heavy metals in the study area were natural sources, agricultural fertilizer sources, industrial coal sources, and domestic transportation sources, with the contribution rates of 81.31%, 15.45%, 2.74%, and 0.50%, respectively; 84.25% of the sites in the study area were at slight ecological risk, whereas the moderate risk and strong risk sites accounted for 14.96% and 0.79%, respectively. Among them, Cd and Hg were the dominant elements of ecological risk in the study area.

Enhanced biological activities of coumarin-functionalized polysaccharide derivatives: Chemical modification and activity assessment.

Natural polysaccharides are abundant and renewable resource, but their applications are hampered by limited biological activity. Chemical modification can overcome these drawbacks by altering their structure. Three series of polysaccharide derivatives with coumarins were synthesized to obtain polysaccharide derivatives with enhanced biological activity. The biological activities were tested, including antioxidant property, antifungal property, and antibacterial property. Based on the results, the inhibitory properties of the coumarin-polysaccharide derivatives were significantly improved over the raw polysaccharide. The IC50 of the inhibition of DPPH, ABTS•+, and superoxide (O2•-) radical-scavenging was 0.06-0.15 mg/mL, 2.3-15.9 µg/mL, and 0.03-0.25 mg/mL, respectively. Compared with the raw polysaccharides, coumarin- polysaccharide derivatives exhibited higher efficacy in inhibiting the growth of tested phytopathogens, showing inhibitory indices of 60.0-93.6 % at 1.0 mg/mL. Chitosan derivatives with methyl and chlorine (Compound 10B and 10C) exhibited significant antibacterial activity against S. aureus (MIC = 31.2 µg/mL), E. coli (MIC = 7.8 µg/mL), and V. harveyi (MIC = 15.6 µg/mL), respectively. The results of the cytotoxicity assay showed no observed cytotoxicity when the RAW 264.7 cells were incubated with the synthesized polysaccharide derivatives at the tested concentrations.

Impaired cardiac pump function assessment with normalized cardiac power using cardiac magnetic resonance in patients with hypertrophic cardiomyopathy.

Background: Cardiac power (CP; CP = 0.222 × cardiac output × mean blood pressure) output in patients with heart failure has been studied previously, but its importance in patients with hypertrophic cardiomyopathy (HCM) remains unclear. The present study aimed to explore the role of normalized CP (normalized CP = CP/ventricle mass) in assessing cardiac function in patients with HCM with normal ejection fraction using cardiac magnetic resonance (CMR). Methods: This cross-sectional study enrolled 99 patients with HCM who underwent CMR from December 2020 to January 2022 at Beijing Anzhen Hospital, and these patients were classified into heart failure or non-heart failure subgroups. Meanwhile, a control group comprising 65 gender- and age-matched healthy volunteers was also enrolled. The baseline clinical characteristics and cardiac functional parameters were compared between the patients with HCM and the controls, and multivariable linear regression analysis was performed to analyze the relationship between normalized CP and the relevant factors. Results: Significantly higher CP (1.19 vs. 1.01 W; P=0.03) but lower normalized CP (0.73 vs. 1.12 W/100 g; P<0.001) were found in patients with HCM as compared with the controls. Multivariable analysis showed that HCM correlated well with normalized CP [ß=-0.235; 95% confidence interval (CI): -0.341 to -0.129; P<0.001]. In the HCM group, there were 34 cases with heart failure and 65 with non-heart failure, and the patients with HCM with heart failure showed similar CP (1.14 vs. 1.24 W; P=0.06) but significantly lower normalized CP (0.54 vs. 0.78 W/100 g; P<0.001). The correlation analysis of normalized CP and functional parameters revealed that normalized CP was inversely correlated with left ventricle mass/body surface area (R=-0.509; 95% CI: -0.646 to -0.341; P<0.001) in patients with HCM. Conclusions: Normalized CP decreased significantly and was negatively correlated with ventricle mass, indicating impaired cardiac pump function in patients with HCM. Normalized CP might play a critical role in detecting and evaluating impaired cardiac pump function in patients with HCM with preserved ejection fraction.

CropQuant-Air: an AI-powered system to enable phenotypic analysis of yield- and performance-related traits using wheat canopy imagery collected by low-cost drones.

As one of the most consumed stable foods around the world, wheat plays a crucial role in ensuring global food security. The ability to quantify key yield components under complex field conditions can help breeders and researchers assess wheat's yield performance effectively. Nevertheless, it is still challenging to conduct large-scale phenotyping to analyse canopy-level wheat spikes and relevant performance traits, in the field and in an automated manner. Here, we present CropQuant-Air, an AI-powered software system that combines state-of-the-art deep learning (DL) models and image processing algorithms to enable the detection of wheat spikes and phenotypic analysis using wheat canopy images acquired by low-cost drones. The system includes the YOLACT-Plot model for plot segmentation, an optimised YOLOv7 model for quantifying the spike number per m2 (SNpM2) trait, and performance-related trait analysis using spectral and texture features at the canopy level. Besides using our labelled dataset for model training, we also employed the Global Wheat Head Detection dataset to incorporate varietal features into the DL models, facilitating us to perform reliable yield-based analysis from hundreds of varieties selected from main wheat production regions in China. Finally, we employed the SNpM2 and performance traits to develop a yield classification model using the Extreme Gradient Boosting (XGBoost) ensemble and obtained significant positive correlations between the computational analysis results and manual scoring, indicating the reliability of CropQuant-Air. To ensure that our work could reach wider researchers, we created a graphical user interface for CropQuant-Air, so that non-expert users could readily use our work. We believe that our work represents valuable advances in yield-based field phenotyping and phenotypic analysis, providing useful and reliable toolkits to enable breeders, researchers, growers, and farmers to assess crop-yield performance in a cost-effective approach.

Assessment of nucleus accumbens impairment in a rat model of postoperative cognitive dysfunction using diffusion tensor imaging.

BACKGROUND: Postoperative cognitive dysfunction (POCD) often occurs in elderly patients, causing depression and other symptoms. Nucleus accumbens (NAc) is involved in depression. We investigate the diffusion tensor imaging (DTI) parameters of NAc in a POCD model of depression. METHODS: Twenty-month-old male Sprague-Dawley (SD) rats were randomly divided into the POCD and Sham groups. The POCD group underwent exploratory laparotomy to establish a POCD depression model, while the Sham group underwent a sham operation. The fractional anisotropy (FA) and mean diffusivity (MD) values of the bilateral NAc, behavioural changes of forced swimming test and sucrose preference rate, and pathological changes of glial fibrillary acidic protein (GFAP) fluorescent intensity were observed at 15 days (D15 ) and 30 days (D30 ) after the operation. RESULTS: The FA value of the bilateral NAc area in the POCD group was lower than that in the Sham group at the two time periods after the operation (P < 0.05). However, the MD value at D30 was higher in the POCD group than in the Sham group (P < 0.05). The FA value in the POCD group was lower at D30 than at D15 (P < 0.05). The floating time was prolonged while the sucrose preference rate was decreased in the POCD group compared with the Sham group (P < 0.05). The floating time in the POCD group was longer at D30 than at D15 . However, the sucrose preference rate in the POCD was lower at D30 than at D15 . The GFAP fluorescent intensity in the bilateral NAc region in the POCD group was higher than in the Sham group (P < 0.05). CONCLUSION: Microstructural changes of the NAc area are associated with POCD related depression. In addition, FA and MD were demonstrated to be effective in diagnosing and monitoring postoperative depression and its severity.

Assessment of combined algal toxicity of TiO2 nanoparticles and organochlorines in karst surface waters.

The widespread use of nanoparticles (NPs) and organic pollutants increases the risk of their coexistence in the aquatic environments. It is uncertain how the combined toxicities of NPs and OCs affect aquatic organisms in surface waters. In this study, the binary combined toxicities of TiO2 NPs with three different organochlorines (OCs)-pentachlorobenzene (PeCB), 3,3,4,4-tetrachlorobiphenyl (PCB-77), and atrazine on Chlorella pyrenoidosa in three karst surface water bodies were investigated. The correlation analysis results indicated that the toxicities of TiO2 NPs and OCs to algae were mainly related to the total organic carbon (TOC) and ionic strength of surface water. Surface water relieved the growth inhibition of the pollutants on algae as compared with ultrapure water (UW). The combined toxic effect caused by the co-exposure of TiO2 NPs-atrazine was synergistic and had an antagonistic effect for TiO2 NPs-PCB-77 in four types of water bodies. However, the co-exposure of TiO2 NPs-PeCB had an additive effect in the Huaxi Reservoir (HX) and synergistic effects in Baihua Lake (BH), Hongfeng Lake (HF), and UW. TiO2 NPs increased the bioaccumulation of OCs by algae. Both PeCB and atrazine significantly increased the bioaccumulation of TiO2 NPs by algae, except for PeCB in HX; however, PCB-77 reduced the bioaccumulation of TiO2 NPs by algae. The toxic effects of TiO2 NPs and OCs on algae in different water bodies were the result of the nature of the pollutants, bioaccumulation, hydrochemical properties, and other factors.

Impact of government subsidies on innovation of Chinese biopharmaceutical firms: Based on kink threshold model.

Do government subsidies achieve the goals of stimulating firm innovation and macro-regulation? Existing studies have not reached a consistent conclusion. We will study the incentive effect of government subsidies on innovation of biopharmaceutical firms, analyze the optimal interval of government subsidies, and improve the efficiency of government subsidies. Thus, based on kink threshold model using data from Chinese biopharmaceutical listed companies from 2013-2019, this study analyzes the impact of government subsidies on innovation inputs and outputs. Government subsidies can stimulate innovation inputs and outputs of biopharmaceutical firms. Meanwhile, such subsidies have a significant threshold effect on innovation inputs and outputs, and there is an optimal interval effect. Additionally, concerning enterprise ownership, government subsidies have a more significant role in promoting innovation of non-state biopharmaceutical firms. Regarding regional differences, such subsidies have a more significant role in promoting innovation of firms in the less economically developed central and western regions. This study reveals the influence pattern of government subsidies, and provides insights and suggestions to formulate subsidy policies and enhance innovation.