Regulation mechanism of endochondral ossification in Rana zhenhaiensis during metamorphosis based on histomorphology and transcriptome analyses.

Endochondral ossification plays a crucial role in the limb development of amphibians. This study explored the ossification sequence in the hindlimb of Rana zhenhaiensis tadpoles and the correlation between thyroid hormones (THs) and endochondral ossification via histomorphology and transcriptional analyses. Our results suggest that ossification of the femur and tibiofibula was initiated during the period of high THs activity (metamorphosis climax). In addition, the results of differentially expressed gene analyses in the hindlimb and tail showed that systemic factors, transcription factors, and locally secreted factors interacted with each other during the metamorphosis climax to regulate the occurrence of endochondral ossification. These results will enrich the morphological data of anurans and provide scientific reference for the evolutionary history of vertebrates.

Variation in the sensitivity of intestine and skin of Bufo gargarizans and Rana chensinensis tadpoles in relation to zinc exposure.

Zinc (Zn) contaminants in the aquatic environment have an intricate impact on amphibians. Amphibian gut and skin microbiota are participated in regulating their normal physiological functions. Here, we investigated the effects of Zn on the gut and skin tissues and microbiota of Bufo gargarizans and Rana chensinensis tadpoles using histological methods and 16S rRNA sequencing technology. Our results showed a decrease in the height of enterocytes and skin epithelial cells after Zn treatment. Furthermore, Zn exposure elicited alterations in the composition and structure of the gut and skin microbiota at the phylum and genus levels in Bufo gargarizans and Rana chensinensis tadpoles. The feature predictions revealed an elevation in the abundance of potentially pathogenic bacteria and stress-tolerant bacteria in the gut and skin of both tadpoles after zinc exposure. We also speculated that microbiota from various species and organs exhibit varying degrees of sensitivity to zinc based on the functional predictions results. In the context of increasing environmental pollution and the global amphibians decline, our research enriches the current understanding of effects of zinc on amphibian microbiota and provides new framework for artificial breeding and amphibian conservation.

Gut microbiota-bile acid crosstalk contributes to intestinal damage after nitrate exposure in Bufo gargarizans tadpoles.

Bile acids (BAs) are amphipathic steroid acids whose production and diversity depend on both host and microbial metabolism. Nitrate (NO3-) is a widespread pollutant in aquatic ecosystems, which can cause rapid changes in microbial community structure and function. However, the effect of gut microbiota reshaped by nitrate­nitrogen (NO3-N) on BAs profiles remains unclarified. To test this, intestinal targeted BAs metabolomics and fecal metagenomic sequencing were performed on Bufo gargarizans tadpoles treated with different concentrations of NO3-N. NO3-N exposure induced a reduction in the abundance of microbiota with bile acid-inducible enzymes (BAIs) and/or hydroxysteroid dehydrogenases (HSDHs), thus inhibiting the conversion of primary BAs to secondary BAs. Inhibition of BAs biotransformation decreased protective hydrophilic BAs (UDCA) and increased toxic hydrophobic BAs (CA and CDCA), which may contribute to intestinal histopathological damage. Moreover, we found that NO3-N treatment increased microbial virulence factors and decreased Glycoside hydrolases, further highlighting the deleterious risk of NO3-N. Overall, this study shed light on the complex interactions of NO3-N, gut microbiota, and BAs, and emphasized the hazardous effects of NO3-N pollution on the health of amphibians.

Effects of ciprofloxacin and levofloxacin on initial colonization of intestinal microbiota in Bufo gargarizans at embryonic stages.

Ciprofloxacin (CIP) and levofloxacin (LEV) are broad-spectrum antibiotics with potent antibacterial activity. Although many studies have shown that antibiotics can lead to gut microbiota disruption, the effects of CIP and LEV on gut microbial colonization at the embryonic stage remain poorly characterized. Here, we evaluated the response of Bufo gargarizans embryos in terms of gut microbiota colonization, growth and developmental stages to CIP and LEV exposure. Embryos treated with 100 µg/L CIP and LEV exhibited significantly reduced diversity and richness of the gut microbiota, as well as altered community structure. Both CIP and LEV treatments resulted in an increase in the pathogenic bacteria Bosea and Aeromonas, and they appeared to be more resistant to CIP than LEV. Additionally, CIP exposure caused reduced total length and delayed the development in B. gargarizans embryos, while LEV increased the total length and promoted embryonic development. The present study revealed the adverse effects of CIP and LEV exposure on host gut microbiota, growth and development during the embryonic stage, and contributed new perspectives to the evaluation of early aquatic ecological risk under CIP and LEV exposure.

Five-year Treatment with Tenofovir Alafenamide Achieves High Rates of Viral Suppression, Alanine Aminotransferase Normalization, and Favorable Bone and Renal Safety in Chinese Chronic Hepatitis B Patients.

Background and Aims: After 3-years (144 week) of double-blind treatment in Chinese chronic hepatitis B patients in two ongoing phase 3 studies, tenofovir alafenamide (TAF) showed similar efficacy to tenofovir disoproxil fumarate (TDF), with improved renal and bone safety. In this study, we aimed to report the 5-year results from 2 years into the open-label TAF treatment phase. Methods: All participants completing the 144-week double-blind treatment were eligible to receive open-label TAF 25 mg once daily up to week 384. Serial analysis of viral suppression (hepatitis B virus DNA <29 IU/mL), alanine aminotransferase normalization, serological responses, and safety outcomes at year 5 (week 240) was performed. Results: The open-label phase included 93% (311/334) of the enrolled participants, which included 212 who switched from double-blind TAF to open-label TAF (TAF-TAF) and 99 who switched from double-blind TDF to open-label TAF (TDF-TAF). Baseline characteristics were comparable. Week 240 viral suppression rates were similar between groups [93.4% vs. 93.9%; difference: -1.5%, (95% CI: -6.4 to -3.5), p=0.857]. Alanine aminotransferase normalization and serological response rates were higher in the TAF-TAF group than in the TDF-TAF group. The frequencies of adverse events and laboratory abnormalities were low and similar between groups. Both groups had similar small numerical declines from baseline in estimated glomerular filtration rate at year 5 (week 240, -2.85 mL/min vs. -3.29 mL/min, p=0.910). The greater declines in renal and bone parameters in the TDF-TAF group through week 144 improved after switching to TAF. Conclusions: The 5-year TAF treatment efficacy was high and similar to that of 3-year TDF followed by 2-year TAF in Chinese chronic hepatitis B patients. Favorable effects on bone and renal parameters were sustained with TAF treatment alone and were observed following the switch from TDF to TAF.

Morphological and Transcriptomic Analyses Reveal the Toxicological Mechanism and Risk of Nitrate Exposure in Bufo gargarizans Embryos.

In recent years, nitrate (NO3-N) pollution in water bodies has been increasing due to the excessive use of nitrogen-based fertilizers. Exposure to NO3-N during the development of amphibian embryos may have lasting effects on the growth and development of individuals and even threaten their survival, but the toxicity mechanism of NO3-N in amphibian embryos prior to thyroid morphogenesis remains unclear. In the present study, Bufo gargarizans was selected as the model organism to investigate the toxic effects of 10 mg/L and 100 mg/L NO3-N exposure (N10 and N100) on amphibian embryos using methimazole (MMI) and exogenous thyroxine (T4) as the reference groups. We found that T4, MMI, N10 and N100 inhibited B. gargarizans embryo growth and development, with MMI and N100 showing the earliest and strongest effects. Transcriptome analysis revealed that MMI and NO3-N (especially N100) significantly downregulated genes related to thyroid morphogenesis and cholesterol metabolism, while upregulating genes related to inflammation and apoptosis. Together, these results contribute to a deeper understanding of the complex mechanisms by which NO3-N disrupts B. gargarizans embryonic development, reveal the potential risks of NO3-N pollution to other aquatic organisms, and provide insights into the conservation of a broader ecosystem.

Pollution characteristics and release mechanism of microplastics in a typical end-of-life vehicle (ELV) recycling base, East China.

Microplastics (MPs) is a novel and significant pollution due to its eco-environmental hazards and ubiquity. In end-of-life vehicle (ELV) recycling base, MPs are widely distributed but have rare reported in scientific literature. In this study, a comprehensive analysis of MPs was conducted in a typical ELV recycling base. MPs were found in all samples at different sampling sites and environmental mediums. A total of 34 polymer types were detected by µ-FTIR, and the main polymers include PE-PP, ABS, polyester resin, nylon, and PEU plastic. MPs were released from the crushing, tearing, and breaking of plastic parts in ELVs. They were in high content in ground dust, with the abundance of 737-29,021 p/5 g D (the average abundance of 5552 ± 6435 p/5 g D). The abundance, shape, color, and size of MPs are related with functional areas of ELV recycling. Heavy metals could be adsorbed on MPs, and their contents on MPs have a significant correlation with those in the corresponding dust samples. At last, some specific MPs control measures, such as changing transportation mode, using dust-proof cloths, and equipping dust removal equipment, have been put forward.

Atherosclerotic cardiovascular disease risk profile of patients with chronic hepatitis B treated with tenofovir alafenamide or tenofovir disoproxil fumarate for 96 weeks.

BACKGROUND: Patients with chronic hepatitis B (CHB) who switch from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) show changes in lipid profiles. AIM: To evaluate how these changes affect cardiovascular risk. METHODS: This pooled analysis, based on two large prospective studies, evaluated fasting lipid profiles of patients with CHB who were treated with TAF 25 mg/day or TDF 300 mg/day for 96 weeks. Patients who fulfilled the American College of Cardiology criteria (age 40-79 years, high-density lipoprotein [HDL] 20-100 mg/dL, total cholesterol [TC] 130-320 mg/dL and systolic blood pressure 90-200 mmHg) required to assess 10-year atherosclerotic cardiovascular disease (ASCVD) risk with baseline lipid data and at least one post-baseline measurement were included in the ASCVD-risk population. The 10-year ASCVD risk was calculated for patients in this population, and changes from baseline to Week 96 were assessed using intermediate- (≥7.5%) and high-risk (≥20%) cut-offs. RESULTS: Among 1632 patients, 620 (38%) met the criteria for the ASCVD-risk population. At Week 96, fasting levels of all lipids, except TC:HDL ratio, were lower with TDF than TAF. No significant increase was observed in overall ASCVD risk or in any ASCVD-risk categories during the 96-week treatment period compared with baseline. A similar proportion of patients in the TAF and TDF treatment groups (1.3% and 2.3%, respectively; p = 0.34) reported cardiovascular events. CONCLUSION: Despite on-treatment differences in lipid profiles with TAF and TDF, predicted cardiovascular risk and clinical events were similar for both groups after 96 weeks.

Effects of perchlorate and exogenous T4 exposures on body condition and endochondral ossification of Rana chensinensis tadpoles.

Perchlorate, as an endocrine-disrupting chemical (EDC), is largely produced and used in the military, fireworks, fertilizers, and other industries and widely exists in water. Although perchlorate is known to destroy the normal function of thyroid hormones (THs) in amphibians and interfere with their growth and development, the impact of TH levels caused by sodium perchlorate (NaClO4) on endochondral ossification and skeletal development is poorly investigated, and the underlying molecular mechanism has not been clarified. The present study aimed to explore the potential effects of NaClO4 and exogenous thyroxine (T4) on the skeletal development of Rana chensinensis tadpoles and elucidate the related molecular mechanisms. Our results showed that histological changes occurred to the femur and tibia-fibula of tadpoles raised in 250 µg/L NaClO4 and 5 µg/L exogenous T4, and the length of their hindlimbs was significantly reduced. In addition, exogenous T4 exposure significantly interfered with the expression of Dio3, TRß, MMP9, MMP13, and Runx2, inhibiting the endochondral ossification process. Therefore, we provide robust evidence that the changes in TH levels caused by NaClO4 and exogenous T4 will adversely affect the endochondral ossification and skeletal development of R. chensinensis tadpoles.

Construction of a backpropagation starlight atmospheric refraction model based on ray tracing.

The atmospheric refraction model is a vital part of the refraction navigation system. A more accurate model needs to be constructed for the navigation algorithm design and simulation verification. Based on the Thermosphere, Ionosphere, Mesosphere Energetics and Dynamics/Sounding of the Atmosphere using Broadband Emission Radiometry (TIMED/SABER) dataset and the geometrical ray propagation law, a ray tracing algorithm is proposed to calculate the atmospheric refraction angles. Moreover, a neural network starlight atmospheric refraction model (BP model) is constructed to better describe the relationship between time, location, and refraction angle. Compared with the experimental data, the bias error of the backpropagation (BP) model is 1.06 ' ' , which is better than the 3.75 ' ' of the traditional model. It indicates that the BP model is exact and has important guiding significance for the starlight refraction navigation technology.

Tenofovir alafenamide and tenofovir disoproxil fumarate reduce incidence of hepatocellular carcinoma in patients with chronic hepatitis B.

Background & Aims: Antiviral therapy may attenuate the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). We aimed to explore how tenofovir alafenamide (TAF) and tenofovir disoproxil fumarate (TDF) affect HCC risk in patients with CHB. Methods: The REACH-B, aMAP, and mPAGE-B models were utilized to assess HCC risk in patients with CHB from two global randomized-controlled trials evaluating the impact of TAF vs. TDF treatment. Standard incidence ratios (SIRs) were calculated using data from the REACH-B model as a ratio of observed HCC cases in the TAF- or TDF-treated patients vs. predicted HCC cases for untreated historical controls. Proportions of treated patients shifting aMAP and mPAGE-B risk categories between baseline and Week 240 were calculated. Results: Of the 1,632 patients (TAF, n = 1,093; TDF, n = 539) followed for up to 300 weeks, 22 HCC cases developed. Those receiving TAF had an SIR that was lower compared to the SIR of individuals receiving TDF: 0.32 (p <0.001) vs. 0.56 (p = 0.06). In the general study population, individuals without cirrhosis at baseline had an SIR that was lower compared to the SIR of individuals with cirrhosis at baseline: 0.37 (p <0.001) vs. 0.58 (p = 0.15). Of the patients at low risk of HCC at baseline, the majority (97%) remained low risk by mPAGE-B and aMAP scoring at Week 240. Among those at medium or high risk at baseline, substantial portions shifted to a lower risk category by Week 240 (mPAGE-B: 22% and 42%; aMAP: 39% and 63%, respectively). Conclusions: This evaluation provides evidence that treatment with TAF or TDF can reduce HCC risk in patients with CHB, particularly in patients without cirrhosis. Impact and implications: Despite the substantial impact of HCC on long-term outcomes of patients with CHB, the differential risk of HCC development among those receiving treatment with TAF vs. TDF has not been well elucidated. Using three validated risk prediction models, we found that TAF is at least as effective as TDF in reducing HCC risk in patients with CHB. While TDF is well-studied in the context of HCC risk reduction, our novel findings underscore the effectiveness of TAF as a treatment option for patients with CHB. Clinical trial numbers: NCT01940341; NCT02836249; NCT01940471; NCT02836236.

Electrodeposited copper enhanced removal of 2,4-dichlorophenol in batch and flow reaction in Cu@CC-PS-MFC system.

Combination of microbial fuel cell (MFC) and advanced oxidation process (AOP) is promising for pollutant removal. In this paper, Cu0-loaded carbon cloth cathode by electrodeposition (Cu@CC-PS-MFC) was applied to enhance 2,4-dichlorophenol (2,4-DCP) degradation based on persulfate (PS) activation in microbial fuel cell. Cu0 exhibited a typical structure of face-centered cubic metal polyhedron on carbon cloth. The removal of 2,4-DCP by Cu@CC-PS-MFC (75.6%) was enhanced by more than 50% compared to CC-PS-MFC (49.2%) after 1 h of reaction. 30 mg/L 2,4-DCP in Cu@CC-PS-MFC was completely removed and achieved a high mineralization (80.6%) after 9 h of reaction under optimized condition with low dissolved copper ion concentration (0.615 mg/L). Meanwhile, more than 90% removal of 2,4-DCP was stably achieved with flow operation condition (hydraulic residence time of 7.2 h). The change of copper valent state Cu0/Cu2O/CuO was the main mechanism of PS activation with main reactive species of O•H and O21. The bioanode of MFC enhanced the in-situ regeneration of ≡Cu+ and ≡Cu0 on the catalyst surface by transporting electrons, which was believed to contribute to good catalyst lifetime and excellent 2,4-DCP removal. Electrodeposited copper contributes to the enhanced degradation of 2,4-DCP with energy recovery at the same time which can further broaden the application MFC.

Long-term Treatment With Tenofovir Alafenamide for Chronic Hepatitis B Results in High Rates of Viral Suppression and Favorable Renal and Bone Safety.

OBJECTIVES: Results from two Phase 3 studies, through 2 years, in chronic hepatitis B infection (CHB) showed tenofovir alafenamide (TAF) had similar efficacy to tenofovir disoproxil fumarate (TDF) with superior renal and bone safety. Here, we report updated results through 5 years. METHODS: Patients with HBeAg-negative or -positive CHB with or without compensated cirrhosis were randomized (2:1) to TAF 25 mg or TDF 300 mg once daily in double-blind (DB) fashion for up to 3 years, followed by open-label (OL) TAF up to 8 years. Efficacy (antiviral, biochemical, serologic), resistance (deep sequencing of polymerase/reverse transcriptase and phenotyping), and safety, including renal and bone parameters, were evaluated by pooled analyses. RESULTS: Of 1298 randomized and treated patients, 866 receiving TAF (DB and OL) and 432 receiving TDF with rollover to OL TAF at year 2 (n = 180; TDF→TAF3y) or year 3 (n = 202; TDF→TAF2y) were included. Fifty (4%) TDF patients who discontinued during DB were excluded. At year 5, 85%, 83%, and 90% achieved HBV DNA < 29 IU/mL (missing = failure) in the TAF, TDF→TAF3y, and TDF→TAF2y groups, respectively; no patient developed TAF or TDF resistance. Median eGFR (by Cockcroft-Gault) declined < 2.5 mL/min, and mean declines of < 1% in hip and spine bone mineral density were seen at year 5 in the TAF group; patients in the TDF→TAF groups had improvements in these parameters at year 5 after switching to OL TAF. CONCLUSIONS: Long-term TAF treatment resulted in high rates of viral suppression, no resistance, and favorable renal and bone safety.

Effects of perchlorate and exogenous T4 on growth, development and tail resorption of Rana chensinensis.

Endocrine disruptors have been demonstrated to exert adverse effects on growth and development of amphibians by disrupting hormone levels. Tail resorption, which is one of the most remarkable events during amphibian metamorphosis, is closely associated with thyroid hormones levels. However, limited research has been conducted on the effects of endocrine disruptors on tail resorption in amphibians. This study explored the effects of NaClO4 and T4 on the growth, development and tail resorption during the metamorphosis of Rana Chensinensis. The results demonstrated that exposure to NaClO4 led to an increase in body size and a delay in metamorphosis of R. Chensinensis tadpoles. Histological analysis revealed that both NaClO4 and exogenous T4 exposure resulted in thyroid gland injury, and NaClO4 treatment delayed the degradation of notochord and muscles, thereby delaying tail resorption. Moreover, transcriptome sequencing results showed that apoptosis-related genes (APAF1, BAX and CASP6) and cell component degradation-related genes (MMP9 and MMP13) were highly expressed in the T4 exposure group, and the expression of oxidative stress-related genes (SOD and CAT) was higher in the NaClO4 exposure group. Taken together, both NaClO4 and exogenous T4 affect tail resorption in R. Chensinensis, thereby affecting their adaptation to terrestrial life. The present study will not only provide a reference for future experimental research on the effects of other endocrine disruptors on the growth, development and tail resorption of amphibians but will also provide insights into environmental protection and ecological risk assessment.

Bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir, emtricitabine, and tenofovir disoproxil fumarate for initial treatment of HIV-1 and hepatitis B coinfection (ALLIANCE): a double-blind, multicentre, randomised controlled, phase 3 non-inferiority trial.

BACKGROUND: For most adults with HIV-1 and hepatitis B virus (HBV) coinfection, initial recommended treatment is a tenofovir-containing antiretroviral regimen, but no randomised studies have compared tenofovir disoproxil fumarate with tenofovir alafenamide. We aimed to investigate whether bictegravir, emtricitabine, and tenofovir alafenamide is non-inferior to dolutegravir, emtricitabine, and tenofovir disoproxil fumarate for viral suppression in individuals with HIV-1 and HBV coinfection at 48 and 96 weeks. METHODS: We did this randomised, double-blind, active-controlled, phase 3, non-inferiority trial at 46 outpatient centres in China, Dominican Republic, Hong Kong, Japan, Malaysia, South Korea, Spain, Taiwan, Thailand, Turkey, and the USA. Eligible participants were treatment-naive adults (aged ≥18 years) with plasma HIV-1 RNA of at least 500 copies per mL and plasma HBV DNA of at least 2000 IU/mL. Participants were randomly assigned (1:1) to receive daily oral bictegravir 50 mg, emtricitabine 200 mg, and tenofovir alafenamide 25 mg, or dolutegravir 50 mg, emtricitabine 200 mg, and tenofovir disoproxil fumarate 300 mg, each with corresponding matching placebo. Randomisation was stratified by hepatitis B e antigen (HBeAg) status (positive vs negative), HBV DNA (<8 vs ≥8 log10 IU/mL), and CD4 count (<50 vs ≥50 cells per µL) at screening. All investigators, participants, and staff providing treatment, assessing outcomes, and collecting data were masked to study treatment for 96 weeks. Coprimary endpoints were the proportion of participants with plasma HIV-1 RNA less than 50 copies per mL (defined by the US Food and Drug Administration snapshot algorithm) and plasma HBV DNA less than 29 IU/mL (using the missing-equals-failure approach) at week 48, with a prespecified non-inferiority margin of -12%. Coprimary endpoints were assessed in the full analysis set, which included all randomly assigned participants who received at least one dose of study drug and had at least one post-baseline HIV-1 RNA or HBV DNA result while on study drug. Safety endpoints were assessed in all randomly assigned participants who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, NCT03547908. FINDINGS: Between May 30, 2018 and March 16, 2021, 381 participants were screened, of whom 243 initiated treatment (121 in the receive bictegravir, emtricitabine, and tenofovir alafenamide group; 122 in the dolutegravir, emtricitabine, and tenofovir disoproxil fumarate group). At week 48, both endpoints met the criteria for non-inferiority: 113 (95%) of 119 participants in the bictegravir, emtricitabine, and tenofovir alafenamide group and 111 (91%) of 122 participants in the dolutegravir, emtricitabine, and tenofovir disoproxil fumarate group had HIV-1 RNA less than 50 copies per mL (difference 4·1, 95% CI -2·5 to 10·8; p=0·21), and 75 (63%) of 119 participants in the bictegravir, emtricitabine, and tenofovir alafenamide group versus 53 (43%) of 122 participants in the dolutegravir, emtricitabine, and tenofovir disoproxil fumarate group had HBV DNA suppression (difference 16·6, 5·9 to 27·3; nominal p=0·0023). Drug-related adverse events up to week 96 occurred in 35 (29%) of 121 participants in the bictegravir, emtricitabine, and tenofovir alafenamide group and 34 (28%) of 122 participants in the dolutegravir, emtricitabine, and tenofovir disoproxil fumarate group. One (1%) of 121 participants in the bictegravir, emtricitabine, and tenofovir alafenamide group reported a serious adverse event (cryptococcal meningitis attributed to immune reconstitution inflammatory syndrome) that was deemed to be treatment-related. INTERPRETATION: Coformulated bictegravir, emtricitabine, and tenofovir alafenamide is an effective therapy for adults with HIV-1 and HBV coinfection starting antiviral therapy. FUNDING: Gilead Sciences.

Regulation mechanisms underlying tail resorption in Bufo gargarizans metamorphosis.

Anurans have been excellent organisms for studying amphibian metamorphosis. Tail resorption is a remarkable event that occurs during amphibian metamorphosis. Although tail resorption has been previously studied in other anurans like Xenopus laevis and Rana chensinensis, there is no report on Bufo gargarizans. This paper thus explored the mechanism of tail resorption during metamorphosis in Bufo gargarizans tadpoles through some biological research methods. Histological results showed that the tail tissues of tadpoles gradually degraded as metamorphosis progressed. RNA sequencing analysis was performed to examine the expression level and functional enrichment of differentially expressed genes in the tail. In addition, we analyzed the mRNA expression levels of genes related to tail resorption by quantitative real-time polymerase chain reaction. We also speculated on three pathways that participate in the regulation of tail resorption based on the above results. The present study might provide a theoretical basis and novel insights for further research of complex molecular mechanisms of tail resorption in amphibians.

Impairment of bile acid metabolism and altered composition by lead and copper in Bufo gargarizans tadpoles.

Lead (Pb) and copper (Cu) are two common heavy metal contaminants in environments, and liver is recognized as one of the main target organs for toxicity of Pb and Cu in animal organisms. Bile acids play a critical role in regulating hepatic metabolic homeostasis by activating farnesoid X receptor (Fxr). However, there were few studies on the interactions between bile acids and liver pathology caused by heavy metals. In this work, the histopathological changes, targeted metabolome and transcriptome responses in the liver of Bufo gargarizans tadpoles to Pb and/or Cu were examined. We found that exposure to Pb and/or Cu altered the hepatic bile acid profile, resulting in increased hydrophobicity and toxicity of the bile acid pool. And the expression of genes involved in bile acid metabolism and their downstream signaling pathways in the liver were significantly altered by Pb and/or Cu exposure. The alteration of bile acid profiles and the expression of genes related to bile acid metabolism might induce oxidative stress and inflammation, ultimately inducing hepatocyte injury observed in the histological sections. To our knowledge, this is the first study to provide histological, biochemical, and molecular evidence for establishing the link between Pb and Cu exposure, disturbances in hepatic bile acid metabolism, and liver injury.

Detachment of Dodecane from Silica Surfaces with Variable Surface Chemistry Studied Using Molecular Dynamics Simulation.

The adsorption and detachment processes of n-dodecane (C12H26) molecules were studied on silica surfaces with variable surface chemistry (Q2, Q3, Q4 environments), using molecular dynamics simulations. The area density of the silanol groups varied from 9.4 to 0 per nm2. The shrinking of the oil-water-solid contact line was a key step for the oil detachment, due to water diffusion on the three-phase contact line. The simulation results showed that oil detachment was easier and faster on a perfect Q3 silica surface which had (≡Si(OH))-type silanol groups, due to the H-bond formation between the water and silanol groups. When the surfaces contained more Q2 crystalline type which had (≡Si(OH)2)-type silanol groups, less oil detached, due to the formations of H-bonds among the silanol groups. There were no silanol groups on the Si-OH 0 surface. Water cannot diffuse on the water-oil-silica contact line, and oil cannot detach from the Q4 surface. The detachment efficiency of oil from the silica surface not only depended on the area density, but also on the types of silanol groups. The density and type of silanol groups depend on the crystal cleavage plane, particle size, roughness, and humidity.

Fate of 15N-labelled urea as affected by long-term manure substitution.

Quantifying the fate of fertilizer nitrogen (N) is essential to develop more sustainable agricultural fertilization practices. However, the fate of chemical fertilizer N, particularly in long-term manure substitution treatment regimes, is not fully understood. The present study aimed to investigate the fate of 15N-labelled urea in a chemical fertilizer treatment (CF, 240 kg 15N ha-1) and N manure 50 % substitution treatment (1/2N + M, 120 kg 15N ha-1 + 120 kg manure N ha-1) in two continuous crop seasons, based on a 10-year long-term experiment in the North China Plain (NCP). The results showed that manure substitution greatly enhanced 15N use efficiency (15NUE) (39.9 % vs. 31.3 %) and suppressed 15N loss (6.9 % vs. 7.5 %) compared with the CF treatment in the first crop. However, the N2O emissions factor in the 1/2N + M treatment was increased by 0.1 % (0.5 kg 15N ha-1 for CF vs. 0.4 kg 15N ha-1 for 1/2N + M) compared with the CF treatment, although N leaching and NH3 volatilization rates decreased by 0.2 % (10.8 kg 15N ha-1 for CF vs. 5.1 kg 15N ha-1 for 1/2N + M) and 0.5 % (6.6 kg 15N ha-1 for CF vs. 2.8 kg 15N ha-1 for 1/2N + M), respectively. In which, only NH3 volatilization presented significantly difference between treatments. It is important to note that in the second crop, the residual 15N in soil (0-20 cm) remained mostly in the soil for the CF (79.1 %) and the 1/2N + M treatment (85.3 %), and contributed less to crop N uptake (3.3 % vs. 0.8 %) and leached losses (2.2 % vs. 0.6 %). This proved that manure substitution could enhance the stabilization of chemical N. These results suggested that long-term manure substitution effectively increases NUE, suppresses N loss, and improves N stabilization in soil, but negative impacts such as N2O emissions due to climate change should be investigated further.

Studies of a novel bone-targeted nano drug delivery system with a HAP core-PSI coating structure for tanshinol injection.

Tanshinol (Tan) has good therapeutic effects on osteoporosis, fracture, and bone trauma repair. However, it is easily oxidised, has low bioavailability and a short half-life. To solve these problems, the study aimed to develop a novel bone-targeted nano-sustained-release drug delivery system PSI-HAPs for the systemic administration of Tan. This proposed system has hydroxyapatite (HAP) as the core to load drug and polysuccinimide (PSI), PEG-PSI (Polyethylene glycol, PEG), and ALN-PEG-PSI (Alendronate sodium, ALN) as the coating materials to form nanoparticles. The article examines the various PSI-HAPs' entrapping efficiency (EE, %), drug loading capacity (DLC, %), and distribution to determine the best PSI-HAP formulation in vivo. The in vivo experiment showed that the ALN-PEG-PSI-HAP (ALN-PEG/PSI molar ratio = 1:20) was the best preparation due to its higher distribution on bone (120 h) and lower distribution in the other tissues. The determined preparation was a uniformly spherical or sphere-like nanoparticle with a negative zeta potential. Additionally, it exhibited pH-sensitive drug release in PBS based on an in vitro drug release test. The proposed PSI-HAP preparations were prepared in the water solution using a facile preparation process without ultrasound, heating, and other conditions, which can significantly affect the stability of drugs.