PRMT4 interacts with NCOA4 to inhibit ferritinophagy in cisplatin-induced acute kidney injury.

Cisplatin-induced acute kidney injury (AKI) is commonly seen in the clinical practice, and ferroptosis, a type of non-apoptotic cell death, plays a pivotal role in it. Previous studies suggested that protein arginine methyltransferase 4 (PRMT4) was incorporated in various bioprocesses, but its role in renal injuries has not been investigated. Our present study showed that PRMT4 was highly expressed in renal proximal tubular cells, and it was downregulated in cisplatin-induced AKI. Besides, genetic disruption of PRMT4 exacerbated, while its overexpression attenuated, cisplatin-induced redox injuries in renal proximal epithelia. Mechanistically, our work showed that PRMT4 interacted with NCOA4 to inhibit ferritinophagy, a type of selective autophagy favoring lipid peroxidation to accelerate ferroptosis. Taken together, our study demonstrated that PRMT4 interacted with NCOA4 to attenuate ferroptosis in cisplatin-induced AKI, suggesting that PRMT4 might present as a new therapeutic target for cisplatin-related nephropathy.

Fluoride impairs vascular smooth muscle A7R5 cell lines via disrupting amino acids metabolism.

Given the insidious and high-fatality nature of cardiovascular diseases (CVDs), the emergence of fluoride as a newly identified risk factor demands serious consideration alongside traditional risk factors. While vascular smooth muscle cells (VSMCs) play a pivotal role in the progression of CVDs, the toxicological impact of fluoride on VSMCs remains largely uncharted. In this study, we constructed fluorosis model in SD rats and A7R5 aortic smooth muscle cell lines to confirm fluoride impaired VSMCs. Fluoride aggravated the pathological damage of rat aorta in vivo. Then A7R5 were exposed to fluoride with concentration ranging from 0 to 1200 µmol/L over a 24-h period, revealing a dose-dependent inhibition of cell proliferation and migration. The further metabolomic analysis showed alterations in metabolite profiles induced by fluoride exposure, notably decreasing organic acids and lipid molecules level. Additionally, gene network analysis underscored the frequency of fluoride's interference with amino acids metabolism, potentially impacting the tricarboxylic acid (TCA) cycle. Our results also highlighted the ATP-binding cassette (ABC) transporters pathway as a central element in VSMC impairment. Moreover, we observed a dose-dependent increase in osteopontin (OPN) and α-smooth muscle actin (α-SMA) mRNA level and a dose-dependent decrease in ABC subfamily C member 1 (ABCC1) and bestrophin 1 (BEST1) mRNA level. These findings advance our understanding of fluoride as a CVD risk factor and its influence on VSMCs and metabolic pathways, warranting further investigation into this emerging risk factor.

Tellurium(IV) Halide Achieving Effective Nonlinear-Optical Activity: The Role of Chiral Ligands and Lattice Distortion.

Chiral organic-inorganic hybrid metal halides are a promising class of nonlinear-optical materials with unique optical properties and flexible crystal structures. However, the structures and properties of chiral hybrid tellurium halides, especially second harmonic generation (SHG), have not been reported. Here, by introducing chiral organic molecule (R/S)-methylbenzylammonium (R/S-MBA), we synthesized a pair of novel zero-dimensional (0D) chiral tellurium-based hybrid halides with noncentrosymmetric space group C2, (R/S-MBA)2TeCl6 (R/S-Cl). Single-crystal X-ray diffraction analysis and solid-state circular dichroism (CD) spectra confirm that R/S-Cl shows obvious enantiomer enrichment. Moreover, the resulting chiral products present an efficient SHG response. Interestingly, through manipulation of halogen atoms, two pairs of achiral tellurium halides, (R/S-MBA)2TeBr6 (R/S-Br) and (R/S-MBA)2TeI6 (R/S-I), were obtained, both of which crystallize in the centrosymmetric space group R3̅. It is noteworthy that R/S-I has a narrow band gap of 1.55 eV, which is smaller than that of most 0D metal halides and comparable to that of three-dimensional lead halide, showing its potential as a highly efficient light absorber.

Highly Selective Protic-Solvent-Mediated Organic-Inorganic Hybrid Cuprous Bromides Achieving Structural Transformation.

The potential application of stimuli-responsive hybrid copper halides in information storage and switch devices has generated significant interest. However, their transformation mechanism needs to be further studied deeply. Herein, two zero-dimensional (0D) organic-inorganic hybrids, namely, (TBA)CuBr2 (1) with linear [CuBr2]- units and (TBA)2Cu4Br6 (2) with [Cu4Br6]2- clusters (TBA+ = (C4H9)4N+), are synthesized using simple solvent evaporation approaches. Interestingly, upon exposure to distinct protic solvents, such as methanol, ethanol, ethylene glycol, or hot water, 1 undergoes a transformation into 2 with varying degrees of transition, accompanied by a change in luminescence color from cyan to orange (or mixed color) under high-energy emission (e.g., 254 nm) excitation. Hot water can trigger 1 to completely transform into 2 because of its large contact angle difference in the solvents. Furthermore, 2 can be converted back to 1 through a simple solid-state mechanochemical reaction. Additionally, the structure of 2 remains unchanged even after immersion in 80 °C H2O for 168 h due to the dense organic framework. This study provides valuable insights for exploring reversible structural transformation materials in the 0D metal halide system.

Risk assessment of imported malaria in China: a machine learning perspective.

BACKGROUND: Following China's official designation as malaria-free country by WHO, the imported malaria has emerged as a significant determinant impacting the malaria reestablishment within China. The objective of this study is to explore the application prospects of machine learning algorithms in imported malaria risk assessment of China. METHODS: The data of imported malaria cases in China from 2011 to 2019 was provided by China CDC; historical epidemic data of malaria endemic country was obtained from World Malaria Report, and the other data used in this study are open access data. All the data processing and model construction based on R, and map visualization used ArcGIS software. RESULTS: A total of 27,088 malaria cases imported into China from 85 countries between 2011 and 2019. After data preprocessing and classification, clean dataset has 765 rows (85 * 9) and 11 cols. Six machine learning models was constructed based on the training set, and Random Forest model demonstrated the best performance in model evaluation. According to RF, the highest feature importance were the number of malaria deaths and Indigenous malaria cases. The RF model demonstrated high accuracy in forecasting risk for the year 2019, achieving commendable accuracy rate of 95.3%. This result aligns well with the observed outcomes, indicating the model's reliability in predicting risk levels. CONCLUSIONS: Machine learning algorithms have reliable application prospects in risk assessment of imported malaria in China. This study provides a new methodological reference for the risk assessment and control strategies adjusting of imported malaria in China.

Assistive device utilization among disabled elderly in China: A cross-sectional study.

OBJECTIVE: This study aimed to examine the characteristics of assistive device users and influencing factors among disabled elderly in China. METHODS: A total of 13,510 disabled elderly in Sichuan Province were surveyed. Disability was assessed using the Barthel Activities of Daily Living Scale, mental status, sensory perception, and social engagement evaluation. Univariate analysis and logistic regression analysis were employed to identify the impact factors. RESULTS: The prevalence of assistive device utilization among participants was 79.2% (10,700/13,510, 95% CI 78.5%-79.9%), with the wheelchair being the most commonly used device. Various factors were found to influence the usage of the device, including disability level, somatic disability, age, caregivers, income, caregiver fees, and living situation (p < .05). Additionally, several factors were identified associated with the frequency of device usage, such as somatic disability, education background, income, caregiver fees, living situation, access to acquire assistive devices, duration of assistive device usage, education on assistive devices, and satisfaction level (p < .05). CONCLUSIONS: The use of assistive devices among elderly individuals in China is prevalent. There are many factors that affect the use of assistive devices, which can provide a reference for the formulation of policies in the field of assistive devices.

Trichinella spiralis dipeptidyl peptidase 1 suppressed macrophage cytotoxicity by promoting M2 polarization via the STAT6/PPARγ pathway.

Trichinella spiralis dipeptidyl peptidase 1 (TsDPP1), or cysteine cathepsin C, is a secretory protein that is highly expressed during the infective larvae and adult worm stages in the intestines. The aim of this study was to investigate the mechanism by which recombinant TsDPP1 (rTsDPP1) activates macrophages M2 polarization and decreases macrophage cytotoxicity to kill newborn larvae via ADCC. RAW264.7 macrophages and murine peritoneal macrophages were used in this study. The results of the immunofluorescence test (IFT) and confocal microscopy showed that rTsDPP1 specifically bound to macrophages, and the binding site was localized on the cell membrane. rTsDPP1 activated macrophage M2 polarization, as demonstrated by high expression levels of Arg1 (M2 marker) and M2-related genes (IL-10, TGF-ß, CD206 and Arg1) and high numbers of CD206+ macrophages. Furthermore, the expression levels of p-STAT6, STAT6 and PPARγ were obviously increased in rTsDPP1-treated macrophages, which were evidently abrogated by using a STAT6 inhibitor (AS1517499) and PPARγ antagonist (GW9662). The results indicated that rTsDPP1 promoted macrophage M2 polarization through the STAT6/PPARγ pathway. Griess reaction results revealed that rTsDPP1 suppressed LPS-induced NO production in macrophages. qPCR and flow cytometry results showed that rTsDPP1 downregulated the expression of FcγR I (CD64) in macrophages. The ability of ADCC to kill newborn larvae was significantly decreased in rTsDPP1-treated macrophages, but AS1517499 and GW9662 restored its killing capacity. Our results demonstrated that rTsDPP1 induced macrophage M2 polarization, upregulated the expression of anti-inflammatory cytokines, and inhibited macrophage-mediated ADCC via activation of the STAT6/PPARγ pathway, which is beneficial to the parasitism and immune evasion of this nematode.

Cluster-Centered Excited-State-Induced Bright Low-Energy Emissive Hybrid Copper Iodide Constructing Stable White LEDs.

Herein, we successfully synthesized a stable copper iodide hybrid with a 0D structure, (C20H20P)2Cu2I4, in which [Cu2I4]2- dimers with a short Cu-Cu distance (2.64 Å) are isolated and surrounded by [C20H20P]+ organic cations. Bright broadband yellow emission (576 nm) featuring a wide excitation range from 240 to 450 nm was achieved, along with a large Stokes shift (211 nm), long-lived lifetime (1.99 µs), and zero self-absorption. The results combined with crystal structure, spectroscopy analysis, and theoretical studies reveal that a cluster-centered excited state is responsible for this yellow emission. Importantly, the structure of (C20H20P)2Cu2I4 remains unchanged even after soaking in water for 30 days or heating at 80 °C for 240 h due to the intermolecular interaction. Furthermore, a stable white LED showing a naturally correlated color temperature (CCT) of 6573 K and CIE color coordinate of (0.31, 0.37) was also demonstrated. This work demonstrates efficient light emitters based on lead-free and stable metal halides for lighting, providing an important reference for the development of stable, high-performance metal halide phosphors.

Dual Monomeric Inorganic Units Constructed Bright Emissive Zero-Dimensional Antimony Chlorides with Solvent-Induced Reversible Structural Transition.

A5M2X11 and A3M2X9 families (A = monovalent organic cation; M = trivalent metal; X = halogen) are receiving increasing attention because of their combination of easy solution processability and superior ferroelectricity properties. However, synthesizing highly efficient A5M2X11 and A3M2X9-type fluorophores with multiple monomeric inorganic units and achieving their structural interconversion remains challenging. Here, we report two novel zero-dimensional (0D) antimony halides, (C10H16N)5Sb2Cl11·C2H3N (1) and (C10H16N)3Sb2Cl9 (2), which not only contain two distinct [SbXn]3-n units but also have excellent orange (590 nm) and yellow-green emission (540 nm) with high PLQY of 17.7% and 31.5%, respectively. Interestingly, a reversible structural conversion could be triggered by acetonitrile steam stimulation, accompanied by luminescence switching properties. This work not only enriches the structure of hybrid Sb-based halides but also provides the possibility of well-known A5M2X11 and A3M2X9 families as structural transformation materials.

Geopolymer composite spheres derived from graphene-modified fly ash/slag: Facile synthesis and removal of lead ions in wastewater.

Geopolymer composite spheres derived from potassium-activated graphene-modified slag/fly ash powder were produced in a polyethylene glycol (PEG 400) solvent. The effect of graphene type (graphene oxide (GO) and few-layered graphene (GNP)) on the pore structure and lead ions (Pb2+) removal performance of the spheres were evaluated. The results showed that the composite spheres modified with GOs (0.1-0.4 wt%) and GNPs (1-4 wt%) could be spheroidized with an improved performance to adsorb Pb2+ in solution. The graphene-containing spheres reached a maximum BET surface area of 68.85 m2/g. Pseudo-second-order and Langmuir isotherm models could express the adsorption process, which was controlled by both monolayer adsorption and chemisorption. The obtained spheres also showed high adsorption capacities for Ni2+, Cu2+, Zn2+ and Cd2+ ions. Chemical, physical, electrostatic, ion exchange and cation-π interaction were attributed to the adsorption mechanism of the spheres. The spheres showed good cycling ability compared to those without graphene, which had potential application in heavy metal wastewater treatment.

Mass balance study of [14C]SHR0302, a selective and potent JAK1 inhibitor in humans.

SHR0302, a selective JAK1 inhibitor developed by Jiangsu Hengrui Pharmaceutical Co., was intended for the treatment of rheumatoid arthritis. In this study, we evaluated the pharmacokinetics, mass balance, and metabolism of SHR0302 in six healthy Chinese male subjects after a single 8 mg (80 µCi) oral dose of [14C]SHR0302.SHR0302 was absorbed rapidly (Tmax = 0.505 h), and the average t1/2 of the SHR0302-related components in plasma was approximately 9.18 h. After an oral dose was administered, the average cumulative excretion of the radioactive components was 100.56% ± 1.51%, including 60.95% ± 11.62% in urine and 39.61% ± 10.52% in faeces.A total of 16 metabolites were identified. In plasma, the parent drug SHR0302 accounted for 90.42% of the total plasma radioactivity. In urine, SHR161279 was the main metabolite, accounting for 33.61% of the dose, whereas the parent drug SHR0302 only accounted for 5.1% of the dose. In faeces, the parent drug SHR0302 accounted for 23.73% of the dose, and SHR161279 was the significant metabolite, accounting for 5.67% of the dose. In conclusion, SHR0302-related radioactivity was mainly excreted through urine (60.95%) and secondarily through faeces (39.61%).The metabolic reaction of SHR0302 in the human body is mainly through mono-oxidation and glucuronidation. The main metabolic location of SHR0302 in the human body is the pyrrolopyrimidine ring.

Underwater Target Detection Based on Parallel High-Resolution Networks.

A parallel high-resolution underwater target detection network is proposed to address the problems of complex underwater scenes and limited target feature extraction capability. First, a high-resolution network (HRNet), a lighter high-resolution human posture estimation network, is used to improve the target feature representation and effectively reduce the semantic information lost in the image during sampling. Then, the attention module (A-CBAM) is improved to capture complex feature distributions by modeling the two-dimensional space in the activation function stage through the introduction of the flexible rectified linear units (FReLU) activation function to achieve pixel-level spatial information modeling capability. Feature enhancement in the spatial and channel dimensions is performed to improve understanding of fuzzy targets and small target objects and to better capture irregular and detailed object layouts. Finally, a receptive field augmentation module (RFAM) is constructed to obtain sufficient semantic information and rich detail information to further enhance the robustness and discrimination of features and improve the detection capability of the model for multi-scale underwater targets. Experimental results show that the method achieves 81.17%, 77.02%, and 82.9% mean average precision (mAP) on three publicly available datasets, specifically underwater robot professional contest (URPC2020, URPC2018) and pattern analysis, statistical modeling, and computational learning visual object classes (PASCAL VOC2007), respectively, demonstrating the effectiveness of the proposed network.

[Research progress on active ingredients of animal-derived traditional Chinese medicine in treatment of allergic rhinitis].

Allergic rhinitis(AR) is a common chronic inflammatory disease of the upper respiratory tract. Due to its high prevalence, high recurrence rate, and lack of a definitive cure, it is considered a global health issue by the World Health Organization. The pathogenesis of AR is complex and mainly involves B cells, helper T cells, eosinophils, basophils, macrophages, as well as the cytokines and inflammatory mediators they secrete. Clinical treatment primarily focuses on inhibiting inflammatory mediators such as histamine and leukotrienes. In recent years, active ingredients of animal-derived traditional Chinese medicine(TCM) have shown unique advantages and potential in AR treatment thanks to their high safety, specificity, selectivity, and biopotency. This study systematically reviewed the therapeutic effects and mechanisms of active ingredients and mixed extracts from animal-derived TCM, such as bovine spleen, honeycomb, bee venom, maggot, and human placenta, which have been shown by modern pharmacological research to regulate the immune function in AR, providing a reference for further exploration and clinical development of active ingredients from animal-derived TCM. Studies have found that the active ingredients from animal-derived TCM can produce definite therapeutic effects in AR by modulating multiple immune balances in the body, with great clinical prospects. However, their mechanisms of action still require further investigation, and the quality control techniques for effective ingredients need to be improved. Currently, the research on active ingredients from animal-derived TCM in China has adopted an interactive system consisting of "traditional medical experience-based research, bioinformatics and artificial intelligence predictions, and validation and development through new experimental techniques". Based on this system, animal-derived TCM can combine modern scientific and technological means to maximize the therapeutic effects of active ingredients and serve the clinical application of AR in a more efficient and innovative manner.

Norepinephrine promotes glioma cell migration through up-regulating the expression of Twist1.

BACKGROUND: Glioma cells are characterized by high migration ability, resulting in aggressive growth of the tumors and poor prognosis of patients. It has been reported that the stress-induced hormone norepinephrine (NE) contributes to tumor progression through mediating a number of important biological processes in various cancers. However, the role of NE in the regulation of glioma migration is still unclear. Epithelial-to-mesenchymal transition (EMT) is one of the most important steps for tumor migration and metastasis. Twist1, as a key regulator of EMT, has been found to be elevated during glioma migration. But it is still unknown whether Twist1 is involved in the effect of NE on the migration of glioma cells. METHODS: Wound healing assay and transwell assay were conducted to evaluate the migration of glioma cells upon different treatments. The mesenchymal-like phenotype and the expression of Twist1 after NE treatment were assessed by cell diameters, real-time PCR, western blot and immunofluorescence staining. The gain-and loss-of-function experiments were carried out to investigate the biological function of Twist1 in the migration induced by NE. Finally, the clinical significance of Twist1 was explored among three public glioma datasets. RESULTS: In this study, our finding revealed a facilitative effect of NE on glioma cell migration in a ß-adrenergic receptor (ADRB)-dependent way. Mechanistically, NE induced mesenchymal-like phenotype and the expression of Twist1. Twist1 overexpression promoted glioma cells migration, while knockdown of Twist1 abolished the discrepancy in the migration ability between NE treated glioma cells and control cells. In addition, the clinical analysis demonstrated that Twist1 was up-regulated in malignant gliomas and recurrent gliomas, and predicted a poor prognosis of glioma patients. CONCLUSIONS: NE enhanced the migration ability of glioma cells through elevating the expression of Twist1. Our finding may provide potential therapeutic target for protecting patients with glioma from the detrimental effects of stress biology on the tumor progression.

Proteases secreted by Trichinella spiralis intestinal infective larvae damage the junctions of the intestinal epithelial cell monolayer and mediate larval invasion.

The intestinal epithelium is the first natural barrier against Trichinella spiralis larval invasion, but the mechanism of larval invasion of the gut epithelium is not fully elucidated. The aim of this study was to investigate whether the excretory/secretory proteins (ESPs) of T. spiralis intestinal infective larvae (IIL) degrade tight junction (TJ) proteins, to assess the main ESP proteases hydrolysing TJ proteins using various enzyme inhibitors and to define the key invasive factors in IIL invasion of the gut epithelium. The results of immunofluorescence, Western blot and Transwell assays showed that serine proteases and cysteine proteases in the ESPs played main roles in hydrolysing occludin, claudin-1 and E-cad and upregulating claudin-2 expression. Challenge infection results showed that IIL expulsion from the gut at 12 hpi was significantly higher in mice which were infected with muscle larvae (ML) treated with a single inhibitor (PMSF, E-64, 1,10-Phe or pepstatin) or various mixtures containing PMSF and E-64 than in mice in the PBS group or the groups treated with an inhibitor mixture not containing PMSF and E-64 (P < 0.0001). At 6 days post-infection, mice which were infected with ML treated with PMSF, E-64, 1,10-Phe or pepstatin exhibited 56.30, 64.91, 26.42 and 31.85% reductions in intestinal adult worms compared to mice in the PBS group (P < 0.0001). The results indicate that serine proteases and cysteine proteases play key roles in T. spiralis IIL invasion, growth and survival in the host and that they may be main candidate target molecules for vaccines against larval invasion and development.

Pi-inducedin-situaggregation of sevelamer nanoparticles for vascular embolization.

Decades have witnessed rapid progress of polymeric materials for vascular embolic or chemoembolic applications. Commercially available polymeric embolics range from gelatin foam to synthetic polymers such as poly(vinyl alcohol). Current systems under investigation include tunable, bioresorbable microspheres composed of chitosan or poly(ethylene glycol) derivatives,in situgelling liquid embolics with improved safety profiles, and radiopaque embolics that are trackablein vivo. In this paper, we proposed a concept of 'responsive embolization'. Sevelamer, clinically proved as an inorganic phosphate binder, was ground into nanoparticles. Sevelamer nanoparticle is highly mobile and capable of swelling and aggregating in the presence of endogenous inorganic phosphate, thereby effectively occluding blood flow in the vessel as it was administered as an embolic agent for interventional therapy. Moreover, citrated sevelamer nanoparticles delayed the aggregation, preferable to penetrate deeply into the capillary system. On the rabbit VX2 liver cancer model, both sevelamer particles aggregates occlude the tumor feeding artery, but backflow was found for the pristine one, thereby citrate passivation of sevelamer nanoparticles endows it have potential from 'bench to bedside' as a new type of vascular embolic.

High expression of HHLA2 predicts poor prognosis in medullary thyroid carcinoma.

BACKGROUND: Human endogenous retrovirus-H long terminal repeat-associating protein 2 is a newly identified immune checkpoint molecule that was aberrantly expressed in many malignant tumors. However, its expression in medullary thyroid carcinoma is still unclear. This study aimed to investigate the human endogenous retrovirus-H long terminal repeat-associating protein 2 expression in medullary thyroid carcinoma tissues and to evaluate the relationships between its expression and clinicopathologic together with prognostic relevance. METHODS: Using 51 surgical specimens obtained from medullary thyroid carcinoma patients, the expression levels of the human endogenous retrovirus-H long terminal repeat-associating protein 2 protein in medullary thyroid carcinoma tumor tissues and adjacent noncancerous tissues were measured by immunohistochemistry, and its correlations with clinicopathologic and prognostic features were analyzed. Status of CD8+ tumor infiltrating lymphocytes was also investigated. RESULTS: The results showed that human endogenous retrovirus-H long terminal repeat-associating protein 2 was only detected in tumor tissues, and 31.4% of the medullary thyroid carcinoma patients had high expression of human endogenous retrovirus-H long terminal repeat-associating protein 2. High human endogenous retrovirus-H long terminal repeat-associating protein 2 expression was significantly associated with lymph node metastasis and advanced American Joint Committee on Cancer stages (P = 0.005). There existed an inverse trend between human endogenous retrovirus-H long terminal repeat-associating protein 2 expression and CD8+ tumor infiltrating lymphocytes infiltration in medullary thyroid carcinoma tumor samples (P = 0.042). The log-rank test showed a shorter disease-free survival in patients with high human endogenous retrovirus-H long terminal repeat-associating protein 2 expression (P = 0.002). The disease-free survival rates were also significantly low in cases of medullary thyroid carcinoma with lymph node metastasis, American Joint Committee on Cancer stages III-IV and multifocality. Multivariate Cox analysis confirmed that human endogenous retrovirus-H long terminal repeat-associating protein 2 acted as an independent predictive factor in the disease-free survival of medullary thyroid carcinoma patients (hazard ratio = 4.138, 95% confidence interval: 1.027-16.667, P = 0.046). CONCLUSIONS: Taken together, human endogenous retrovirus-H long terminal repeat-associating protein 2 is highly expressed in medullary thyroid carcinoma patients and is a poor prognostic biomarker of disease-free survival of medullary thyroid carcinoma patients.

Absorption, distribution, metabolism, and excretion of [14C]TPN729 after oral administration to rats.

TPN729, a novel phosphodiesterase type 5 (PDE5) inhibitor for the treatment of erectile dysfunction (ED), is in phase II clinical trials in China. Previous studies suggested that TPN729 possesses promising therapeutic value. In previous non-radiolabeled rat excretion studies, the recovery of TPN729 and its major metabolites accounted for approximately 8.58% of the administration dose in urine and faeces by 48 h post-dose.To solve this problem and further study the metabolism of TPN729 in rats, we used the radio-isotopic tracing technique for the first time. In this study, the mass balance, tissue distribution, and metabolism of TPN729 were evaluated in rats after a single oral dose of 25 mg/kg [14C]TPN729 (150 µCi/kg).At 168 h post-dose, the mean total radioactivity recovery of the dose was 92.13%. Faeces was the major excretion route, accounting for 74.63% of the dose, and urine excretion accounted for 17.50%. After oral administration of [14C]TPN729, radioactivity was widely distributed in all examined tissues, and a higher radioactivity concentration was observed in the stomach, large intestine, lung, liver, small intestine, and eyes. The concentration of drug-related materials were similar in plasma and blood cells. A total of 51 metabolites were identified in rat plasma, urine, faeces, and bile, and the predominant metabolically susceptible position of TPN729 was the pyrrolidine moiety. The main metabolic pathways were N-dealkylation, oxidation, and dehydrogenation.In summary, we solved the previous problem of low drug recovery, elucidated the major excretion pathway, determined the tissue distribution patterns, and investigated the metabolism of TPN729 in rats by using a radioisotopic tracing technique.

Characterization of a novel aminopeptidase P from Trichinella spiralis and its participation in the intrusion of intestinal epithelial cells.

Aminopeptidases P are metalloproteases belonging to the M24 peptidase family. It specifically hydrolyzes the N-terminus of polypeptides free of acidic amino acids, and plays an important role in the nutrition, metabolism and growth of parasites. The aim of this study was to characterize a novel Trichinella spiralis aminopeptidase P (TsAPP) and to investigate its functions in the invasion of T. spiralis. TsAPP contained two domains of creatinase (a creatinase N and creatinase N2) and a domain of peptidase M24C and APP. The complete TsAPP sequence was cloned and expressed in Escherichia coli BL21 cells. The recombinantly produced TsAPP was used to raise polyclonal antibodies that were subsequently used to detect the expression of the protein in the different life stages of T. spiralis. TsAPP was expressed in various T. spiralis stages. TsAPP was primarily localized in the cuticle, stichosome and intrauterine embryos of this nematode. rTsAPP has an enzymatic activity of a natural aminopeptidase P to hydrolyze the substrate H-Ala-Pro-OH. rTsAPP promoted the larval intrusion of intestinal epithelium cells (IECs). The results showed that TsAPP is involved in the T. spiralis intrusion of IECs and it might be a potential candidate vaccine target against Trichinella infection.

Effectiveness of endoscopic intranasal incision reduction for nasal fractures.

PURPOSE: To report our experience using endoscopic intranasal incision reduction (EIIR) for nasal fractures and to assess effectiveness of the method. METHODS: 30 patients who underwent EIIR were retrospectively analysed. All the patients were examined by three-dimensional computed tomography (3D CT), acoustic rhinometry and rhinomanometry, preoperatively and postoperatively at 1 month. The visual analogue scale (VAS) was used to assess the preoperative aesthetics and nasal airflow satisfaction and at 1, 3 and 6 months postoperatively. VAS aesthetic satisfaction was also scored by two junior doctors. RESULTS: 3D CT showed that the fracture fragments fitted well in 30 patients postoperatively at 1 month. VAS aesthetics and nasal airflow scores were significantly improved postoperatively at 1, 3 and 6 months compared with preoperative scores (P < 0.01). The VAS aesthetic scores from the two surgeons were also significantly improved (P < 0.01). The minimal cross-sectional area increased from 0.39 ± 0.13 to 0.64 ± 0.13 (P < 0.001), the nasal volume increased from 4.65 ± 0.86 to 6.37 ± 0.94 (P < 0.001) and the total inspiratory airway resistance of the bilateral nasal cavity median decreased from 0.467 Pa/mL/s to 0.193 Pa/mL/s (P < 0.001). There were no technique-related intraoperative complications. CONCLUSION: EIIR was a practical choice, and the aesthetics and nasal airflow were significantly improved in patients with overlapped and displaced bone fragments, patients with fractures of the frontal process of the maxilla (FFPM), patients who underwent failed CR and patients beyond the optimal temporal window.