CREG1 attenuates doxorubicin-induced cardiotoxicity by inhibiting the ferroptosis of cardiomyocytes.

OBJECTIVE: Doxorubicin (DOX)-induced cardiotoxicity limits the application of DOX in cancer patients. Currently, there is no effective prevention or treatment for DOX-induced cardiotoxicity. The cellular repressor of E1A-stimulated genes (CREG1) is a cardioprotective factor that plays an important role in the maintenance of cardiomyocytes differentiation and homeostasis. However, the role and mechanism of CREG1 in DOX-induced cardiotoxicity has not yet been elucidated. METHODS: In vivo, C57BL/6J mice, CREG1 transgenic and cardiac-specific CREG1 knockout mice were used to establish a DOX-induced cardiotoxicity model. H&E staining, Masson's trichrome, WGA staining, real-time PCR, and western blotting were performed to examine fibrosis and ferroptosis in the myocardium. In vitro, neonatal mouse cardiomyocytes (NMCMs) were cultured and stimulated with DOX, CREG1-overexpressed adenovirus, and small interfering RNA was used to establish CREG1 overexpression or knockdown cardiomyocytes. Transcriptomics, real-time PCR, western blotting, and immunoprecipitation were used to examine the roles and mechanisms of CREG1 in cardiomyocytes ferroptosis. RESULTS: The mRNA and protein levels of CREG1 were reduced in the hearts and NMCMs after DOX treatment. CREG1 overexpression alleviated myocardial damage and inhibited DOX-induced ferroptosis in the myocardium. CREG1 deficiency in the heart aggravated DOX-induced cardiotoxicity and ferroptosis. In vitro, CREG1 overexpression inhibited cardiomyocytes ferroptosis induced by DOX, and CREG1 knockdown aggravated DOX-induced cardiotoxicity. Mechanistically, CREG1 inhibited the mRNA and protein expression of pyruvate dehydrogenase kinase 4 (PDK4) by regulating the F-box and WD repeat domain containing 7 (FBXW7)-forkhead box O1 (FOXO1) pathway. PDK4 deficiency reversed the effects of CREG1 knockdown on cardiomyocytes ferroptosis following DOX treatment. CONCLUSION: CREG1 alleviated DOX-induced cardiotoxicity by inhibiting ferroptosis in cardiomyocytes. Our findings may help clarify the new roles of CREG1 in the development of DOX-induced cardiotoxicity.

Addressing challenges associated with nitrification inhibitors.

Despite global yield benefits from the use of nitrification inhibitors (NIs), the uncertainties and limitations surrounding NIs warrant more attention. Understanding the impacts of NIs on the health of organisms, people, and ecosystems is also crucial. Here we present a global budget, current challenges, and future research priorities of NIs.

JNJ-77242113, a highly potent, selective peptide targeting the IL-23 receptor, provides robust IL-23 pathway inhibition upon oral dosing in rats and humans.

The interleukin (IL)-23 pathway is a pathogenic driver in psoriasis, psoriatic arthritis, and inflammatory bowel disease. Currently, no oral therapeutics selectively target this pathway. JNJ-77242113 is a peptide targeting the IL-23 receptor with high affinity (KD: 7.1 pM). In human cells, JNJ-77242113 potently and selectively inhibited proximal IL-23 signaling (IC50: 5.6 pM) without impacting IL-12 signaling. JNJ-77242113 inhibited IL-23-induced interferon (IFN)γ production in NK cells, and in blood from healthy donors and psoriasis patients (IC50: 18.4, 11 and 9 pM, respectively). In a rat trinitrobenzene sulfonic acid-induced colitis model, oral JNJ-77242113 attenuated disease parameters at doses ≥ 0.3 mg/kg/day. Pharmacologic activity beyond the gastrointestinal tract was also demonstrated. In blood from rats receiving oral JNJ-77242113, dose-dependent inhibition of ex vivo IL-23-stimulated IL-17A production was observed. In an IL-23-induced rat skin inflammation model, JNJ-77242113 inhibited IL-23-induced skin thickening and IL-17A, -17F and -22 gene induction. Oral dosing of JNJ-77242113 in healthy human volunteers inhibited ex vivo IL-23-stimulated IFNγ production in whole blood. Thus, JNJ-77242113 provided selective, systemic IL-23 pathway inhibition in preclinical models which translated to pharmacodynamic activity in healthy human volunteers, supporting the potential for JNJ-77242113 as a selective oral therapy for IL-23-driven immune-mediated diseases.

[Pedigree Analysis of Hereditary Coagulation Factor XII Deficiency Caused by Compound Heterozygous Mutation p.Gly175Cys and p.Gly542Ser of F12 Gene].

OBJECTIVE: To analyze the clinical phenotype and gene mutation of a genetic coagulation factor XII (FXII) deficiency pedigree and explore the molecular pathogenesis. METHODS: The activated partial thromboplastin time (APTT) and FXII activity (FXII:C) were detected by clotting method. The FXII antigen (FXII:Ag) was tested with ELISA. All exons and flanks of F12 gene were determined by Sanger sequencing. ClustalX-2.1-win, PROVEAN and Swiss-Pdb Viewer software were used to analyze the conservatism of amino acids at the mutant site, forecast whether the mutant amino acids were harmful and confirm the influence of the mutation on protein structure. RESULTS: The APTT of the proband prolonged to 71.3 s. The FXII:C and FXII:Ag were decreased to 5% and 6%, respectively. There were two heterozygous missense mutations c.580G>T and c.1681G>A detected in exon 7 and exon 14 of F12 gene, resulting in p.Gly175Cys and p.Gly542Ser, severally. Proband's father carried the p.Gly175Cys heterozygous mutation, while mother, brother and daughter had the p.Gly542Ser heterozygous mutation. Software analysis showed that both Gly175 and Gly542 were conserved, the two mutations were harmful and when mutations had occurred, the corresponding sites affected the protein local structure. CONCLUSION: The p.Gly175Cys and p.Gly542Ser compound heterozygous mutations are the molecular pathogenesis of the hereditary coagulation FXII deficiency pedigree. The p.Gly175Cys mutation has been detected for the first time in the world.

Global evidence for joint effects of multiple natural and anthropogenic drivers on soil nitrogen cycling.

Global soil nitrogen (N) cycling remains poorly understood due to its complex driving mechanisms. Here, we present a comprehensive analysis of global soil δ15N, a stable isotopic signature indicative of the N input-output balance, using a machine-learning approach on 10,676 observations from 2670 sites. Our findings reveal prevalent joint effects of climatic conditions, plant N-use strategies, soil properties, and other natural and anthropogenic forcings on global soil δ15N. The joint effects of multiple drivers govern the latitudinal distribution of soil δ15N, with more rapid N cycling at lower latitudes than at higher latitudes. In contrast to previous climate-focused models, our data-driven model more accurately simulates spatial changes in global soil δ15N, highlighting the need to consider the joint effects of multiple drivers to estimate the Earth's N budget. These insights contribute to the reconciliation of discordances among empirical, theoretical, and modeling studies on soil N cycling, as well as sustainable N management.

Electrocardiogram prediction of atrial fibrillation risk after stroke: A protocol for systematic review and meta-analysis.

BACKGROUND: Atrial fibrillation (AF) is one of the most common clinical arrhythmias. This study aims to predict the risk of post-stroke AF through electrocardiographic changes in sinus rhythm. METHODS: We searched the MEDLINE (PubMed) and EMBASE databases to identify relevant research articles published until August 2023. Prioritized items from systematic reviews and meta-analyses were screened, and data related to AF detection rate were extracted. A meta-analysis using a random-effects model was conducted for data synthesis and analysis. RESULTS: A total of 32 studies involving electrocardiograms (ECG) were included, with a total analysis population of 330,284 individuals. Among them, 16,662 individuals (ECG abnormal group) developed AF, while 313,622 individuals (ECG normal group) did not. ECG patterns included terminal P-wave terminal force V1, interatrial block (IAB), advanced interatrial block, abnormal P-wave axis, pulse rate prolongation, and atrial premature complexes. Overall, 15,762 patients experienced AF during the study period (4.77%). In the ECG abnormal group, the proportion was 14.21% (2367/16,662), while in the control group (ECG normal group), the proportion was 4.27% (13,395/313,622). The pooled risk ratio for developing AF was 2.45 (95% confidence interval [CI]: 2.02-2.98, P < .001), with heterogeneity (I2) of 95%. The risk ratio values of alAB, P-wave terminal force V1, interatrial block, abnormal P-wave axis, pulse rate prolongation and atrial premature complexes were 4.12 (95% CI, 2.99-5.66), 1.47 (95% CI, 1.19-1.82), 2.54 (95% CI, 1.83-3.52), 1.70 (95% CI, 0.98-2.97), 2.65 (95% CI, 1.88-3.72), 3.79 (95% CI, 2.12-6.76), respectively. CONCLUSION: There is a significant correlation between ECG patterns and the occurrence of AF. The alAB exhibited the highest level of predictability for the occurrence of AF. These indicators support their use as screening tools to identify high-risk individuals who may benefit from further examinations or empirical anticoagulation therapy following stroke.

Life expectancy and mental related burden of disease among people living with HIV/AIDS.

Mental health problems leads to serious disease burden among people living with HIV/AIDS (PLHIV). The study aimed at measuring the mental disorders-caused burden of disease based on PLHIV in mainland China. The data used was from the national HIV/AIDS case reporting system, life expectancy (LE) and LE-eliminated suicide were evaluated by the life-table method. The total YLLs and YLLs caused by suicide in each age group were calculated. The disability weights were estimated by the scale of depression symptoms (CES-D) from the multi-center cross-sectional survey, then calculated the corresponding YLDs as a burden of mental illness among PLHIV. Results showed that the LE had been prolonged by implementing antiviral therapy for PLHIV. The proportion of YLLs caused by suicide was the highest (5·46%) in the 15-24 age group. The YLDs in the 25-34 age group were the highest. The YLLs caused by suicide in males were higher than those in the same age group of females. The YLDs and YLLs were higher in heterosexual-infected PLHIV than in homosexual-infected PLHIV, except for YLLs in the 25-34 age group. In summary, this study first provided localized data on the disease burden caused by mental health problems among PLHIV.

CuCo2O4 nanoneedle arrays growth on carbon cloth as a non-enzymatic electrochemical sensor with low detection limit ketoprofen recognition.

An electrochemical sensor for detecting ketoprofen was constructed by in-situ grown copper cobaltate (CuCo2O4) nanoneedle arrays on a carbon cloth (CC) substrate. The resulting porous nanoneedle arrays not only expose numerous electrochemically active sites but also significantly enhance the electrochemical apparent active area and current transmission efficiency. By leveraging its electrochemical properties, the sensor achieves an impressive detection limit for ketoprofen of 0.7 pM, with a linear range spanning from 2 pM ~ 2 µM. Furthermore, the sensor exhibits remarkable reproducibility, anti-interference capabilities, and stability. Notably, the developed sensor also performed ketoprofen detection on real samples (including drug formulations and wastewater) and demonstrated excellent recognition ability. These exceptional performances can be attributed to the direct growth of CuCo2O4 nanoneedle arrays on the CC substrate, which facilitates a robust electrical connection, provides abundant electrocatalytic active sites, and expands the apparent active area. Consequently, these improvements contribute to the efficient trace detection capabilities of the ketoprofen sensor.

Downregulation of miR-337-3p in hypoxia/reoxygenation neuroblastoma cells increases KCTD11 expression.

Neurodegeneration is linked to the progressive loss of neural function and is associated with several diseases. Hypoxia is a hallmark in many of these diseases, and several therapies have been developed to treat this disease, including gene expression therapies that should be tightly controlled to avoid side effects. Cells experiencing hypoxia undergo a series of physiological responses that are induced by the activation of various transcription factors. Modulation of microRNA (miRNA) expression to alter transcriptional regulation has been demonstrated to be beneficial in treating multiple diseases, and in this study, we therefore explored potential miRNA candidates that could influence hypoxia-induced nerve cell death. Our data suggest that in mouse neuroblasts Neuro-2a cells with hypoxia/reoxygenation (H/R), miR-337-3p is downregulated to increase the expression of Potassium channel tetramerization domain containing 11 (KCTD11) and subsequently promote apoptosis. Here, we demonstrate for the first time that KCTD11 plays a role in the cellular response to hypoxia, and we also provide a possible regulatory mechanism by identifying the axis of miR-337-3p/KCTD11 as a promising candidate modulator of nerve cell survival after H/R exposure.

Meta-analysis shows the impacts of ecological restoration on greenhouse gas emissions.

International initiatives set ambitious targets for ecological restoration, which is considered a promising greenhouse gas mitigation strategy. Here, we conduct a meta-analysis to quantify the impacts of ecological restoration on greenhouse gas emissions using a dataset compiled from 253 articles. Our findings reveal that forest and grassland restoration increase CH4 uptake by 90.0% and 30.8%, respectively, mainly due to changes in soil properties. Conversely, wetland restoration increases CH4 emissions by 544.4%, primarily attributable to elevated water table depth. Forest and grassland restoration have no significant effect on N2O emissions, while wetland restoration reduces N2O emissions by 68.6%. Wetland restoration enhances net CO2 uptake, and the transition from net CO2 sources to net sinks takes approximately 4 years following restoration. The net ecosystem CO2 exchange of the restored forests decreases with restoration age, and the transition from net CO2 sources to net sinks takes about 3-5 years for afforestation and reforestation sites, and 6-13 years for clear-cutting and post-fire sites. Overall, forest, grassland and wetland restoration decrease the global warming potentials by 327.7%, 157.7% and 62.0% compared with their paired control ecosystems, respectively. Our findings suggest that afforestation, reforestation, rewetting drained wetlands, and restoring degraded grasslands through grazing exclusion, reducing grazing intensity, or converting croplands to grasslands can effectively mitigate greenhouse gas emissions.

Synergy of Active Sites and Charge Transfer in Branched WO3/W18O49 Heterostructures for Enhanced NO2 Sensing.

Achieving reliable detection of trace levels of NO2 gas is essential for environmental monitoring and protection of human health protection. Herein, a thin-film gas sensor based on branched WO3/W18O49 heterostructures was fabricated. The optimized WO3/W18O49 sensor exhibited outstanding NO2 sensing properties with an ultrahigh response value (1038) and low detection limit (10 ppb) at 50 °C. Such excellent sensing performance could be ascribed to the synergistic effect of accelerated charge transfer and increased active sites, which is confirmed by electrochemical impedance spectroscopy and temperature-programmed desorption characterization. The sensor exhibited an excellent detection ability to NO2 under different air quality conditions. This work provides an effective strategy for constructing WO3/W18O49 heterostructures for developing NO2 gas sensors with an excellent sensing performance.

Reverse diversity-biomass patterns in grasslands are constrained by climates and stoichiometry along an elevational gradient.

Diversity and biomass play an important role in grassland ecosystem functions. However, diversity and biomass are variable because of their high sensitivity to environmental change in natural ecosystems. How plant diversity, biomass, and driving factors (climates, soils, and plants) in grasslands vary with environmental change remains unclear. We conducted intensive fieldwork (≈1000 km transect) on plant diversity, biomass, and associated drivers (i.e., climates, soils, and plants) to identify the patterns of diversity and biomass along an elevational gradient (50-4000 m) in grasslands of southwest China. Grassland biomass decreased significantly, but grassland diversity increased with increasing elevation. Consequently, a significant reverse pattern between biomass and diversity was detected along an elevational gradient. We also observed that the reverse pattern was primarily driven by the shifts in climates (i.e., temperature and precipitation), leaf stoichiometric traits (i.e., leaf N:P ratio), and soil properties (i.e., soil N content) along the elevational gradient. Our results contradicted previous studies on the positive diversity-biomass relationships, suggesting that previous studies might weaken the effects of climatic factors and plant stoichiometry under environmental change. These findings revealed that the reverse pattern between diversity and biomass in grasslands was shaped by the combined effects (climates, plants, soils) in grasslands, thus providing new insights into the debates and predictions on the diversity and biomass in grasslands under climate change.

Shifts in soil ammonia-oxidizing community maintain the nitrogen stimulation of nitrification across climatic conditions.

Anthropogenic nitrogen (N) loading alters soil ammonia-oxidizing archaea (AOA) and bacteria (AOB) abundances, likely leading to substantial changes in soil nitrification. However, the factors and mechanisms determining the responses of soil AOA:AOB and nitrification to N loading are still unclear, making it difficult to predict future changes in soil nitrification. Herein, we synthesize 68 field studies around the world to evaluate the impacts of N loading on soil ammonia oxidizers and nitrification. Across a wide range of biotic and abiotic factors, climate is the most important driver of the responses of AOA:AOB to N loading. Climate does not directly affect the N-stimulation of nitrification, but does so via climate-related shifts in AOA:AOB. Specifically, climate modulates the responses of AOA:AOB to N loading by affecting soil pH, N-availability and moisture. AOB play a dominant role in affecting nitrification in dry climates, while the impacts from AOA can exceed AOB in humid climates. Together, these results suggest that climate-related shifts in soil ammonia-oxidizing community maintain the N-stimulation of nitrification, highlighting the importance of microbial community composition in mediating the responses of the soil N cycle to N loading.

From the dual-dimensional perspective of employee mindfulness and superior trust, explore the influence mechanism of negative workplace gossip on work engagement.

Introduction: As a common phenomenon of workplace negative gossip in organizations, how it affects employees' work engagement is not yet clear, nor what methods can be used to mitigate its negative impact on employees' work engagement. Methods: Based on Conservation of Resource Theory, this study obtained 334 valid employee samples from mainland China enterprises through a three-time lagged research design and explored the mechanism of negative workplace gossip on work engagement from the dual perspectives of employees and supervisors. Results: The results show that: (1) Negative workplace gossip negatively affects employee work engagement. (2) Professional commitment plays a mediating role between negative workplace gossip and employee work engagement. (3) Employee mindfulness negatively moderates the negative impact of workplace negative gossip on professional commitment; superior trust negatively moderates the negative impact of workplace negative gossip on professional commitment. (4) Employee mindfulness and superior trust are further weakened to moderate the negative indirect impact of workplace negative gossip on employee work engagement through professional commitment, and this negative indirect impact is weaker when employees have a higher degree of mindfulness and higher trust in superiors. Discussion: It proposes effective strategies for managing workplace gossip to harness its positive influence and offer practical guidance to enhance employee work engagement.

[Analysis of a Chinese pedigree affected with Hereditary coagulation factor â « deficiency due to compound heterozygous variants of F12 gene].

OBJECTIVE: To analyze the clinical phenotypes and genetic variants of a Chinese pedigree affected with Hereditary coagulation factor Ⅻ (FⅫ) deficiency. METHODS: A pedigree presented at the First Affiliated Hospital of Air Force Medical University on December 24,2021 was selected as the study subject. Activated partial thromboplastin time (APTT) and coagulation factor Ⅻ activity (FⅫ:C) were determine by a clotting method, and FⅫ antigen was detected with an ELISA assay. Following the extraction of genomic DNA, all exons and flanking regions of the F12 gene were subjected to Sanger sequencing. Clustalx-2.1-win, PROVEAN and Swiss-PDB Viewer software was used to analyze the conservation of amino acids at the variant sites, impact of of the variants on the amino acid substitutions and the protein structure. RESULTS: The APTT of the proband has prolonged to 70.2 s. Her FⅫ:C and FⅫ:Ag have decreased to 12% and 13%, respectively. DNA sequencing revealed that the proband has harbored c.346G>A (p.Gly97Ser) and c.1583C>A (p.Ser509Tyr) heterozygous compound missense variants in exons 5 and 13 of the F12 gene, respectively. Her father and sister were heterozygous carriers for the c.346G>A (p.Gly97Ser) variant, whilst her mother and brother were heterozygous for the c.1583C>A (p.Ser509Tyr) variant. CONCLUSION: The c.346G>A (p.Gly97Ser) and c.1583C>A (p.Ser509Tyr) compound heterozygous variants of the F12 gene probably underlay the pathogenesis of hereditary coagulation FⅫ deficiency in this pedigree.

The effect of afforestation type on soil nitrogen dynamics in the riparian zone of the upper Yangtze River of China.

Afforestation is increasingly important in nutrient cycling in riparian ecotones given that ecosystems in riparian zones are susceptible to anthropogenic activities induced by land use change. However, how land use change (e.g., afforestation) with different planting types influences nitrogen (N) dynamics in riparian zones remains unclear. Here, we examined soil N dynamics following afforestation with three types of plantations of pure willow (Salix babylonica), pure mulberry (Morus alba), and the mixed two species paired with adjacent maize croplands in the upper Yangtze River of China. Our results showed afforestation with the two pure species significantly reduced soil total N (TN) concentration. Soil NO3--N concentration was significantly reduced by the willow and mixed-species afforestation, but soil NH4+-N concentration was significantly higher in the willow and mixed woodlands compared to the paired croplands. Soil N concentrations were tightly associated with the potential N transformation rates, which showed a roughly decreasing trend in N mineralization following afforestation. Soil properties, microbial biomass, and extracellular enzymes jointly explained a large proportion of the total variation in soil N concentrations, with soil enzymes largely contributing to N variation in the topsoil and soil properties primarily contributing to N variation in the subsoil. Overall, our results demonstrate that afforestation with different planting types had contrasting effects on soil N content in the riparian zone. These findings provide new insights into the management of afforestation types to retain soil N by mediating soil properties and microbial activities in the riparian zones under future land use change.

Synthesis of Mesoporous Lanthanum-Doped SnO2 Spheres for Sensitive and Selective Detection of the Glutaraldehyde Disinfectant.

Glutaraldehyde disinfectant has been widely applied in aquaculture, farming, and medical treatment. Excessive concentrations of glutaraldehyde in the environment can lead to serious health hazards. Therefore, it is extremely important to develop high-performance glutaraldehyde sensors with low cost, high sensitivity, rapid response, fabulous selectivity, and low limit of detection. Herein, mesoporous lanthanum (La) doped SnO2 spheres with high specific surface area (52-59 m2 g-1), uniform mesopores (with a pore size concentrated at 5.7 nm), and highly crystalline frameworks are designed to fabricate highly sensitive gas sensors toward gaseous glutaraldehyde. The mesoporous lanthanum-doped SnO2 spheres exhibit excellent glutaraldehyde-sensing performance, including high response (13.5@10 ppm), rapid response time (28 s), and extremely low detection limit of 0.16 ppm. The excellent sensing performance is ascribed to the high specific surface area, high contents of chemisorbed oxygen species, and lanthanum doping. DFT calculations suggest that lanthanum doping in the SnO2 lattice can effectively improve the adsorption energy toward glutaraldehyde compared to pure SnO2 materials. Moreover, the fabricated gas sensors can effectively detect commercial glutaraldehyde disinfectants, indicating a potential application in aquaculture, farming, and medical treatment.

Revisiting the relationships between soil nitrous oxide emissions and microbial functional gene abundances.

A conceptual framework proposes that soil N2 O emissions are more likely related to microbial functional gene abundances based on laboratory experiments than in-situ observations. This framework has largely contributed to reconciling the disputation on linking soil N2 O emissions with functional gene abundances, but the direct evidence is lacking. Wei et al. (2023) provided new evidence to support this framework, showing that O2 dynamics were a better predictor of in-situ soil N2 O emissions than were functional gene abundances. Before the observations can inform N2 O modeling and support sustainable nitrogen management, however, some additional efforts are needed to revisit the relationships between in-situ soil N2 O emissions and functional gene abundances.

Fe3+-binding transferrin nanovesicles encapsulating sorafenib induce ferroptosis in hepatocellular carcinoma.

BACKGROUND: Ferroptosis, iron-dependent cell death, is an established mechanism for cancer suppression, particularly in hepatocellular carcinoma (HCC). Sorafenib (SOR), a frontline drug for the treatment of HCC, induces ferroptosis by inhibiting the Solute Carrier family 7 member 11 (SLC7A11), with inadequate ferroptosis notably contributing to SOR resistance in tumor cells. METHODS: To further verify the biological targets associated with ferroptosis in HCC, an analysis of the Cancer Genome Atlas (TCGA) database was performed to find a significant co-upregulation of SLC7A11 and transferrin receptor (TFRC), Herein, cell membrane-derived transferrin nanovesicles (TF NVs) coupled with Fe3+ and encapsulated SOR (SOR@TF-Fe3+ NVs) were established to synergistically promote ferroptosis, which promoted the iron transport metabolism by TFRC/TF-Fe3+ and enhanced SOR efficacy by inhibiting the SLC7A11. RESULTS: In vivo and in vitro experiments revealed that SOR@TF-Fe3+ NVs predominantly accumulate in the liver, and specifically targeted HCC cells overexpressing TFRC. Various tests demonstrated SOR@TF-Fe3+ NVs accelerated Fe3+ absorption and transformation in HCC cells. Importantly, SOR@TF-Fe3+ NVs were more effective in promoting the accumulation of lipid peroxides (LPO), inhibiting tumor proliferation, and prolonging survival rates in HCC mouse model than SOR and TF- Fe3+ NVs alone. CONCLUSIONS: The present work provides a promising therapeutic strategy for the targeted treatment of HCC.

Construction of a model of endometritis in domestic rabbits using equine-derived pathogens and evaluation of therapeutic effect of sensitive drugs.

Pathogenic bacteria were isolated from the uterine lavage fluid of a mare with endometritis. After identification and purification, the pathogenic bacteria were injected into the uterus of rabbits to induce endometritis. Then, anatomical, blood routine, chemical examination, and histopathological examinations were performed on the rabbits. Rabbit uterus was collected, and quantitative polymerase chain reaction (qPCR) was used to detect the mRNA expression of inflammatory factors including IL-1ß, IL-6, and TNF-α in the rabbit uterus. In addition, enzyme-linked immunosorbent assay (ELISA) was used to detect the uterine concentrations of the inflammatory factors IL-1ß, IL-6, and TNF-α. Western Blot was used to detect the protein expressions of NF-kB, IkBα, and TNF-α in the NF-kB pathway. An antibiotic treatment group was also set up to verify the accuracy of the results. The clinical examination results showed that there was a significant increase of leukocytes in the blood of the rabbits in the model group (P < 0.01). The uterus was congested, enlarged, and purulent. The integrity of the uterine lining was destroyed, and there was a significant increase of lymphocytes in the uterus (P < 0.01). The qPCR and ELISA results showed that the expressions of the inflammatory factors IL-1ß, IL-6, and TNF-α in the uterus of rabbits were significantly increased (P < 0.01). Western blot results showed that the inflammatory factors IL-1ß, IL-6, and TNF-α play a role in promoting inflammation through the NF-kB pathway. The results of the test provide a simple, economical, and reliable means of studying the occurrence, development, prevention, and treatment of equine endometritis.