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Xin Xin, Wei Liu, Zhe-Ao Zhang, Ying Han, Ling-Ling Qi, Ying-Ying Zhang, Xin-Tong Zhang, Hong-Xia Duan, Li-Qing Chen, Ming-Ji Jin, Qi-Ming Wang, Zhong-Gao Gao, Wei Huang State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Department of Pharmaceutics, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, People’s Republic of ChinaCorrespondence: Zhong-Gao Gao; Wei HuangState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Xian Nong Tan Street, Beijing, 100050, People’s Republic of ChinaTel +86-10-63026505Email zggao@imm.ac.cn; huangwei@imm.ac.cnBackground: Glioma is the most common primary malignant brain tumor with a dreadful overall survival and high mortality. One of the most difficult challenges in clinical treatment is that most drugs hardly pass through the blood–brain barrier (BBB) and achieve efficient accumulation at tumor sites. Thus, to circumvent this hurdle, developing an effectively traversing BBB drug delivery nanovehicle is of significant clinical importance. Rabies virus glycoprotein (RVG) is a derivative peptide that can specifically bind to nicotinic acetylcholine receptor (nAChR) widely overexpressed on BBB and glioma cells for the invasion of rabies virus into the brain. Inspired by this, RVG has been demonstrated to potentiate drugs across the BBB, promote the permeability, and further enhance drug tumor-specific selectivity and penetration.Methods: Here, we used the RVG15, rescreened from the well-known RVG29, to develop a brain-targeted liposome (RVG15-Lipo) for enhanced BBB permeability and tumor-specific delivery of paclitaxel (PTX). The paclitaxel-cholesterol complex (PTX-CHO) was prepared and then actively loaded into liposomes to acquire high entrapment efficiency (EE) and fine stability. Meanwhile, physicochemical properties, in vitro and in vivo delivery efficiency and therapeutic effect were investigated thoroughly.Results: The particle size and zeta potential of PTX-CHO-RVG15-Lipo were 128.15 ± 1.63 nm and − 15.55 ± 0.78 mV, respectively. Compared with free PTX, PTX-CHO-RVG15-Lipo exhibited excellent targeting efficiency and safety in HBMEC and C6 cells, and better transport efficiency across the BBB in vitro model. Furthermore, PTX-CHO-RVG15-Lipo could noticeably improve the accumulation of PTX in the brain, and then promote the chemotherapeutic drugs penetration in C6luc orthotopic glioma based on in vivo imaging assays. The in vivo antitumor results indicated that PTX-CHO-RVG15-Lipo significantly inhibited glioma growth and metabasis, therefore improved survival rate of tumor-bearing mice with little adverse effect.Conclusion: Our study demonstrated that the RVG15 was a promising brain-targeted specific ligands owing to the superior BBB penetration and tumor targeting ability. Based on the outstanding therapeutic effect both in vitro and in vivo, PTX-CHO-RVG15-Lipo was proved to be a potential delivery system for PTX to treat glioma in clinic.Keywords: glioma, blood–brain barrier, RVG15, liposome, paclitaxel

Based on the fact that C60 is one of the most abundant and readily available molecular configurations in the fullerene family, this paper investigates the effect of doping fullerenes on the dielectric properties of epoxy composites using C60 as a representative. The structure and properties of fullerene molecules are thoroughly examined from the point of view of materials chemistry. The equipment required for the experiment is selected, the experimental sample preparation plan is formulated, and the structure and dielectric properties of the prepared samples are analyzed by corresponding data analysis. The results show that in the range of r less than 1.03 Å, the particle distribution probability of the fullerene-doped epoxy composites in this interval is 0. As r continues to increase, the probability density of the fused C60 epoxy composites is higher than that of the epoxy matrix. The frequency band of 1 MHz has an enhancement of 0.053 and 0.043. However, the dielectric constant of the composite epoxy resin in the high-frequency interval gradually falls back with the increase of filler, while the enhancement of the dielectric constant occurs in the low-frequency interval, and the fullerene is also optimized in terms of the dielectric constant and dielectric loss properties. Fullerene’s excellent dielectric properties have been confirmed by this study, which is important to broaden the epoxy resin market and improve the competitiveness of products.

Objective To explore the potential active components and anti-inflammation mechanism of a Chinese herb from Dong ethnic minority, Madeng'ai (MDA). Methods UPLC-Q-TOF-MS was taken to analyze and identify the major components of MDA. The potential active targets of MDA were retrieved in the Swiss Target Prediction database, and the disease-related targets were searched in the Omim, Disgene and Genecards databases. The common targets of active components and inflammation were obtained for the potential targets of MDA in the treatment against inflammation. The "drug-disease-target" network and protein-protein interaction (PPI) network were separately constructed by Cytoscape 3.9.1 and String database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of the overlapping targets were performed through David database. Finally, RT-qPCR and Western blotting were conducted to determine the mRNA levels of several inflammation-related factors and the possible signaling pathways in RAW264.7 cells after LPS treatment. Results There were 29 compounds identified by UPLC-Q-TOF/MS, and the top 5 were tormentic acid, ellagic acid, procyanidin C1, epicatechin and procyanidin B1. There were 104 core targets of MDA docking inflammation through database retrieval and after duplicate removal, and TNF-α, IL-6, AKT1 and ALB might be the core targets. A total of 761 GO items were enriched, including 600 items concerning biological processes, 52 items on cell components, and 109 items involving molecular functions. KEGG analysis screened out 160 signal pathways, mainly focusing on NF-κB, MAPK, PI3K-AKT and so forth signaling pathways. Compared with the normal control group, the mRNA levels of TNF-α, IL-6, IL-1β and CCL2 were increased significantly in the model group (LPS treatment group)(P < 0.05), and the phosphorylation levels of p38, ERK and JNK were obviously up-regulated (P < 0.05). While, MDA treatment notably declined the mRNA levels of TNF-α, IL-6, IL-1β and CCL2 (P < 0.05), and down-regulated the phosphorylation levels of p38, ERK and JNK when compared with the model group (P < 0.05). Conclusion Our study forecasts that the water extract of MDA, a Chinese traditional herb from Dong minority, has the potential active ingredients in treatment of inflammation, and shows anti-inflammatory effects through multiple pathways, such as MAPK pathway.

The southwestern Ordos Basin is located at the junction of several stable plates, where faults and fractures are relatively developed, and the influence of fractures on the distribution of tight oil reservoirs in the Yanchang Formation is not clear. To solve this problem, the characteristics of fracture development of the Yanchang Formation, southwestern Ordos Basin and its control on hydrocarbon accumulation have been systematically studied using the core, thin section, well logging, productivity, fault and sand body distribution data. The results show that vertical and horizontal bedding fractures are much more developed in the Chang 8 Member compared with the Chang 6 and 7 Members. For horizontal bedding fractures, they are mainly developed in fine sandstone, followed by siltstone, while no horizontal bedding fractures are observed in medium sandstone. This is because horizontal bedding fractures are more common in fine-grained sediments. For vertical fractures, they are also mainly developed in fine sandstone. The controlling factors of fractures include lithology, sand body thickness, sedimentary microfacies and fault–fracture coupling relationship. Fractures are well developed in the fine-grained sandstone of the wing parts of the main river channel due to small compacted space. In the area where multiple river channels intersect, the sand is pure and easy to break. Based on the comprehensive study of sedimentation, structure and fracture, the classification criteria of sweet point reservoir of the Yanchang Formation are determined: sedimentary microfacies of the main river channel and its wing, tectonic location within 1.5 km from the main fault, plane arrangement of right-lateral and right-order faults and developed fractures. The sweet point reservoir can be identified effectively using the developed sweet point screening criteria.

Objective Adrenoleukodystrophy (ALD) is the most common peroxisomal diseases with high clinical and genetic heterogeneity. Our study is to analyze the phenotype and genotype characteristics of adult patients with ALD. Methods A total of 18 adult patients with ALD admitted to Beijing Tiantan Hospital from May 2016 to April 2021 were recruited, and their clinical manifestations, imaging features, and genetic results were comprehensively analyzed. Results Among 18 patients, 6(33%) patients were diagnosed as adrenomyeloneuropathy (AMN), 2(11%) were cerebral AMN, 5(28%) were adult cerebral ALD (ACALD), 2(11%) were childhood cerebral ALD (CCALD), 1(6%) were adolescent cerebral ALD (AdolALD), and 2(11%) were cerebellar variant of ALD. AMN patients presented with adult-onset stiffness and weakness of lower limbs as the initial and main symptoms, and can developed additional cerebral demyelination; In the case of cerebral ALD, ACALD is more common than CCALD and AdolALD. The prominent manifestations were psychiatric disorders, cognitive, and motor impairment. The imaging features were predominantly occipitoparietal involvement or predominantly frontal involvement with or without contrast enhancement marginal to the demyelinated areas; cerebellar ataxia is the main manifestation in patients with cerebellar variant, and the imaging feature was symmetrical involvement of the cerebellar dentate nucleus. Genetically, the most common mutation type was missense mutation (10/18, 55.6%), followed by frameshift mutation (7/18, 38.9%), and splice site mutation (1/18, 5.6%). Moreover, we found five novo mutations, all of which were frameshift mutations. Conclusions AMN is the most common subtype of adult patients with ALD. ACALD is common among the cerebral ALD. The proportion of cerebellar variant might have been underestimated.

In recent years, with the emergence of new research evidence, the domestic and foreign guidelines in the field of gastrointestinal stromal tumors (GISTs) have been updated. The adjusted contents cover almost every link of GISTs management, from GISTs diagnosis, biological behavior, surgical treatment to targeted drug treatment. Since 2020, the NCCN of the United States has separated the contents related to GISTs from the clinical practice guide for soft tissue sarcoma for the first time to form 2021 V.1 versions. The CSCO has also adjusted and upgraded the previous consensus of Chinese experts on the diagnosis and treatment of GISTs to 2020 and 2021 versions of the guidelines for the diagnosis and treatment of GISTs. This opens a new model of accurate diagnosis and treatment of GISTs under the guidance of evidence-based medicine. The listing of new targeted drugs afatinib and ripretinib is expected to get rid of the drug-resistant treatment dilemma of metastatic GISTs, enrich the back-line treatment camp, provide more opportunities for surgical intervention, and then bring survival benefits to patients with advanced GISTs.

Objectives: Clostridium perfringens (C. perfringens) can cause intestinal diseases in livestock and humans, which seriously threatens the healthy development of animal husbandry and human food safety. Here, the characteristics of antimicrobial resistance and molecular typing of ruminant-borne strains of C. perfringens in Xinjiang, China were explored and profiled. Methods: A total of 307 clinical feces collected from ruminants (cattle and sheep) with diarrheal symptoms were screened for C. perfringens. The recovered isolates were characterized in respect to their antimicrobial resistance pattern and molecular typing. Results: A total of 109 isolates of C. perfringens were isolated from 307 clinical feces of ruminants, most of which displayed the multidrug resistance (MDR) phenotype. Demonstration of the quinolone-resistance gene was the highest among the isolates (70.6%). The multiplex PCR typing based on toxin genes showed that type A and type D strains made up 82.6% (90/109) and 17.4% (19/109), among which, the isolates carrying β2 gene occupied 43.3% (39/90) of type A strains and 31.6% (6/19) of type D strains. These isolates were divided into 6 genotypes (I-VI) by enterobacterial repetitive intergenic consensus sequence-based PCR (ERIC-PCR) method. A total of 33 ST types (ST1-ST33) were identified by multilocus sequence typing (MLST) method. Conclusion: C. perfringens isolates with multidrug resistance (MDR) were frequent and circulating in ruminants. Among them, type A-Ⅰ-ST19 was the dominant genotype of C. perfringens, displaying obvious genetic diversity. This study provided important epidemiological data for the risk assessment of food safety associated with ruminant-borne C. perfringens in Xinjiang, China.

BackgroundDue to the imaging mechanism of neutron radiography and the limitation of neutron source, neutron radiography images are prone to lack of contrast, and it is a common method to improve image quality by contrast enhancement algorithm.PurposeThis study aims to solve the problems related to low contrast and loss of details in neutron imaging.MethodsAn adaptive contrast enhancement (ACE) algorithm based on the particle swarm optimization (PSO) was proposed. First of all, the gain factor coefficient was treated as a particle and initializes a particle swarm. Then, the optimal gain factor coefficient with the PSO algorithm was calculated, and the contrast of the high frequency part of neutron images was improved through implementing this optimal gain factor coefficient in ACE algorithm. Finally, several neutron images were processed by this PSO algorithm and compared with the results of traditional optimization algorithm.ResultsThe new algorithm has obvious contrast enhancement effect for different neutron images, and the parameters such as entropy value, gray average gradient value and contrast value of the optimized image are improved compared with the traditional optimization algorithm.ConclusionsThis algorithm can enhance the contrast of image stably, which has practical significance for the wide application of neutron radiography.

Background and Aim: As a tick-borne zoonotic pathogen, Ehrlichia canis has already posed a threat to public health and safety. This study aimed to clarify the prevalence and molecular characteristics of E. canis in pet dogs in Xinjiang, China. Materials and Methods: A total of 297 blood samples of pet dogs and 709 skin ticks (Rhipicephalus sanguineus sensu lato) were subjected to molecular detection using PCR for E. canis 16S rRNA gene, and then, positive samples were amplified, sequenced, and phylogenetically analyzed for E. canis gp36 gene. Results: The PCR detection showed that the positive rate of PCR was 12.12% (36/297) in blood samples and 15.23% (108/709) in tick samples, respectively. Based on the phylogenetic analysis of E. canis gp36 protein, these E. canis strains in different geographical regions of the world can be divided into Genogroup I and Genogroup II. Among them, the Xinjiang epidemic strain XJ-6 and 533, 36, 1055, Kasur1, and Jake strains were clustered into subgroup 1.1 of Genogroup I, while the XJ-2, XJ-21, and XJ-35 strains and the TWN1, TWN4, CM180, and CM196 strains were closely related and belonged to subgroup 2.2 of Genogroup II, displaying high genetic diversity. Conclusion: This is the first study focusing on the molecular epidemiology of E. canis infection in pet dogs, which revealed that E. canis infection had been occurred in Xinjiang, China. More importantly, this study confirmed that the substantial variability in immunoreactive protein gp36 from E. canis strains circulating in pet dogs.

In this paper, we investigate the Cauchy problem for the N – abc family of Camassa-Holm type equation with both dissipation and dispersion. Furthermore, we establish the blow-up result of the positive solutions in finite time under certain conditions on the initial datum. This result complements the early one in the literature, such as [E. Novruzov, Blow-up phenomena for the weakly dissipative Dullin-Gottwald-Holm equation, J. Math. Phys. 54 (2013), no. 9, 092703, DOI 10.1063/1.4820786] and [Z.Y. Zhang, J.H. Huang, and M.B. Sun, Blow-up phenomena for the weakly dissipative Dullin-Gottwald-Holm equation revisited, J. Math. Phys. 56 (2015), no. 9, 092701, DOI 10.1063/1.4930198].

A series of novel perfluoropropan-2-yl-based quinoline derivatives was designed and synthesized utilizing tebufloquin as the lead compound. The structures of all the newly synthesized compounds were confirmed by spectroscopic data 1HNMR, MS and elemental analysis. The results of bioassay indicated that these compounds exhibited potent fungicidal activities against Erysiphe graminis. Especially, compound 8c displayed excellent activity with EC50 value at 1.48 mg / L, which was better than that of the commercialized fungicide --- tebufloquin. The structure-activity relationship for these new compounds was also discussed.

A series of novel imidazo[4,5-b]pyridine derivatives were synthesized and their structures were characterized by NMR spectroscopy, mass spectrometry and elemental analysis. The results of bioassays showed that some compounds exhibit good fungicidal activity against Puccinia polysora In particular, compound 7b showed an EC50 value of 4.00 mg/L, which was comparable with that of tebuconazole. Besides, preliminary structure-activity relationship was discussed.

Optical receivers with potentially high operation bandwidth and low cost have received considerable interest due to rapidly growing data traffic and potential Tb/s optical interconnect requirements. Experimental realization of 65 GHz optical signal detection and 262 GHz intrinsic operation speed reveals the significance role of graphene photodetectors (PDs) in optical interconnect domains. In this work, a novel complementary metal oxide semiconductor post-backend process has been developed for integrating graphene PDs onto silicon integrated circuit chips. A prototype monolithic optoelectronic integrated optical receiver has been successfully demonstrated for the first time. Moreover, this is a firstly reported broadband optical receiver benefiting from natural broadband light absorption features of graphene material. This work is a perfect exhibition of the concept of monolithic optoelectronic integration and will pave way to monolithically integrated graphene optoelectronic devices with silicon ICs for three-dimensional optoelectronic integrated circuit chips.

Metal hydrides are regarded as promising hydrogen-supplying fuel for energetic materials while CL-20 (Hexanitrohexaazaisowurtzitane) and FOX-7 (1,1-Diamino-2,2-dinitroethylene) are typical principal components commonly used in energetic materials. Hence, it is interesting to explore the interactions between them for development of new energetic systems. In this paper, the adsorption and decomposition of CL-20 or FOX-7 molecules on the MgH2 (110) crystal surface were investigated by employing the First-Principles. In total, 18 adsorption configurations for CL-20/MgH2 (110) and 12 adsorption configurations for FOX-7/MgH2 (110) were considered. The geometric parameters for the configurations, adsorption energies, charge transfer, density of states, and decomposition mechanism were obtained and analyzed. In most of the configurations, chemical adsorption will occur. Moreover, the orientation of the nitro-group in CL-20 or FOX-7 with regard to the MgH2 (110) surface plays an important role on whether and how the energetic molecule decomposes. The adsorption and decomposition of CL-20 or FOX-7 on MgH2 could be attributed to the strong charge transfer between Mg atoms in the first layer of MgH2 (110) surface and oxygen as well as nitrogen atoms in the nitro-group of CL-20 or FOX-7 molecules.

Background: To achieve yaws eradication, the use of the new WHO strategy of initial mass treatment with azithromycin and surveillance twice a year needs to be extended everywhere the disease occurs. However, the geographic scope of the disease is unknown. We aimed to synthesise published and unpublished work to update the reported number of people with yaws at national and subnational levels and to estimate at-risk populations. Methods: We searched PubMed and WHO databases to identify published data for prevalence of active and latent yaws from Jan 1, 1990, to Dec 31, 2014. We also searched for ongoing or recently completed unpublished studies from the WHO yaws surveillance network. We estimated yaws prevalence (and 95% CIs). We collected yaws incidence data from official national surveillance programmes at the first administrative level from Jan 1, 2010, to Dec 31, 2013, and we used total population data at the second administrative level to estimate the size of at-risk populations. Findings: We identified 103 records, of which 23 published articles describing 27 studies and four unpublished studies met the inclusion criteria. Prevalence of active disease ranged from 0·31% to 14·54% in yaws-endemic areas, and prevalence of latent yaws ranged from 2·45% to 31·05%. During 2010–13, 256 343 yaws cases were reported to WHO from 13 endemic countries, all of which are low-income and middle-income countries. 215 308 (84%) of 256 343 cases reported to WHO were from three countries—Papua New Guinea, Solomon Islands, and Ghana. We estimated that, in 2012, over 89 million people were living in yaws-endemic districts. Interpretation: Papua New Guinea, Solomon Islands, and Ghana should be the focus of initial efforts at implementing the WHO yaws eradication strategy. Community-based mapping and active surveillance must accompany the implementation of yaws eradication activities. Funding: None.

Precise electro-magnetic parameters are significant in the investigation of characteristic for brushless synchronous starter/generator system, especially the inductance during the starting process.This paper presented an analytical method for inductance calculation, which analysed the influence of stator windings’ parallel structure on inductance calculation and took the skewed slot structure into consideration. Due to the skewed slot structure, applicable two-dimensional coordinate systems were established .This proposed method could save time in calculation according to the simplification to some extent. The results of analytical method were presented and compared with the simulation results. The reason for the differences has been analyzed.

Abstract Purpose To evaluate the efficacy of cytokine-induced killer (CIK) cell therapy in the treatment of hepatocellular carcinoma. Materials and methods Randomized phase II and III trials on CIK cell-based therapy were identified by electronic searches using a combination of "hepatocellular carcinoma" and "cytokine-induced killer cells". Results The analysis showed significant survival benefit (one-year survival, p < 0.001; two-year survival, p < 0.001; median overall survival, p < 0.001) in favor of CIK-based therapy. Comparison of CIK group versus non-CIK group resulted in a significantly prolonged progression-free survival (PFS) (p < 0.01). A favored disease control rate (DCR) and overall response rate (ORR) were also observed in patients receiving CIK cell therapy (p < 0.01). Meanwhile, patients in the CIK group showed better quality of life (QoL), diminished HBV-DNA content and AFP level (p < 0.01). Comparing T-lymphocyte subsets in peripheral blood, the analysis showed the ratio of CD3+, CD4+, CD4+CD8+ and CD3+CD4+ T cells significantly increased in the CIK group, compared with the non-CIK group (p < 0.01). Conclusions CIK cell therapy demonstrated a significant superiority in prolonging the median overall survival, PFS, DCR, ORR and QoL of HCC patients. These results support further larger scale randomized controlled trials for HCC patients with or without the combination of other therapeutic methods.

Abstract Background Avian leukosis virus (ALV) is a major infectious disease that impacts the poultry industry worldwide. Despite intensive efforts, no effective vaccine has been developed against ALV because of mutations that lead to resistant forms. Therefore, there is a dire need to develop antiviral agents for the treatment of ALV infections and RNA interference (RNAi) is considered an effective antiviral strategy. Results In this study, the avian leukosis virus subgroup J (ALV-J) proviral genome, including the gag genes, were treated as targets for RNAi. Four pairs of miRNA sequences were designed and synthesized that targeted different regions of the gag gene. The screened target (i.e., the gag genes) was shown to effectively suppress the replication of ALV-J by 19.0-77.3%. To avoid the generation of escape variants during virus infection, expression vectors of multi-target miRNAs were constructed using the multi-target serial strategy (against different regions of the gag, pol, and env genes). Multi-target miRNAs were shown to play a synergistic role in the inhibition of ALV-J replication, with an inhibition efficiency of viral replication ranging from 85.0-91.2%. Conclusion The strategy of multi-target miRNAs might be an effective method for inhibiting ALV replication and the acquisition of resistant mutations.

Abstract Background Cerebrotendinous xanthomatosis (CTX) is a rare lipid-storage disease. We investigated the clinic manifestation, histopathology and sterol 27-hydroxylase gene (CYP27A1) in a Chinese family with Cerebrotendinous Xanthomatosis (CTX). Case Presentation A 36-year-old female with typical CTX clinical manifestation had Spindle-shaped lipid crystal clefts in xanthomas and "onion-like demyelination" in sural nerve. The patient was compound heterozygote carrying two deletions in exon 1 (c.73delG) and exon 2 (c.369_375delGTACCCA). The family memebers were carriers. Conclusions A Chinese family with Cerebrotendinous Xanthomatosis had typical clinical manifestation. CYP27A1 mutations were found in the proband and all other family members.

Abstract Background Ericaulon buergerianum (Gujingcao) is an ophthalmic, anti-inflammatory and antimicrobial Chinese medicinal herb. This study aims to investigate the neuroprotective effects of Ericaulon buergerianum ethanol extract (EBE) and to elucidate its underlying action mechanism. Methods The viability of dopaminergic (DA) neuron in zebrafish was examined by anti-tyrosine hydroxylase (TH) immunostaining. The locomotor activity of zebrafish was assessed with a digital video tracking system. The viability and cellular damage of the PC12 cells were determined by MTT and LDH assays respectively. The nuclear morphological changes in apoptotic cells were evaluated with DNA staining by Hoechst 33342 dye. Intracellular nitric oxide (NO) was quantified by DAF-FM diacetate staining. The expression of inducible nitric oxide synthase (iNOS) was determined by Western blot. Results EBE inhibited the 6-OHDA-induced decrease in total distance of movement in zebrafish. Pretreatments of EBE (25, 50, 100 and 200 μg/ml) increased the viability of 6-OHDA-damaged PC12 cells in a dose dependent manner. Protection against 6-OHDA-induced nuclear fragmentation and accumulation of apoptotic bodies was also observed in EBE pretreated cells. Anti-oxidative (inhibition of NO production and iNOS expression in PC12 cells in vitro) activities of EBE are related to its neuroprotective effects in 6-OHDA-induced DA neuron damage. Conclusion EBE exhibited significant neuroprotective activities in zebrafish, including recovery of dopaminergic neuron loss caused by 6-OHDA in a dose-dependent manner in vivo, inhibition of 6-OHDA-induced decrease of total distance in movement in zebrafish. The iNOS-NO pathway may be involved.

Abstract In this article, a new adaptive primary user's signal detection algorithm for cognitive radio, which integrates frequency-domain block adaptive filtering with a matrix accumulation estimation, is presented with detailed description' of the concept and process of the algorithm. Then, the performance of the algorithm is analyzed and compared by simulation according to the practical requirement of cognitive radio. The result shows that the proposed detection algorithm can detect weak signals quickly and effectively with higher detection probability.

Abstract Background Radix Puerariae is used in Chinese medicine to treat alcohol addiction and intoxication. The present study investigates the effects of Flos puerariae lobatae water extract (FPE) and its active ingredient puerarin on alcoholism using rodent models. Methods Alcoholic animals were given FPE or puerarin by oral intubation prior or after alcohol treatment. The loss of righting reflex (LORR) assay was used to evaluate sedative/hypnotic effects. Changes of gama-aminobutyric acid type A receptor (GABAAR) subunits induced by alcohol treatment in hippocampus were measured with western blot. In alcoholic mice, body weight gain was monitored throughout the experiments. Alcohol dehydrogenase (ADH) levels in liver were measured. Results FPE and puerarin pretreatment significantly prolonged the time of LORR induced by diazepam in acute alcoholic rat. Puerarin increased expression of gama-aminobutyric acid type A receptor alpha1 subunit and decreased expression of alpha4 subunit. In chronic alcoholic mice, puerarin pretreatment significantly increased body weight and liver ADH activity in a dose-dependent manner. Puerarin pretreatment, but not post-treatment, can reverse the changes of gama-aminobutyric acid type A receptor subunit expression and increase ADH activity in alcoholism models. Conclusion The present study demonstrates that FPE and its active ingredient puerarin have preventive effects on alcoholism related disorders.

Abstract Background While all anti-diabetic agents can decrease blood glucose level directly or indirectly, few are able to protect and preserve both pancreatic beta cell mass and their insulin-secreting functions. Thus, there is an urgent need to find an agent or combination of agents that can lower blood glucose and preserve pancreatic beta cells at the same time. Herein, we report a dual-functional andrographolide-lipoic acid conjugate (AL-1). The anti-diabetic and beta cell protective activities of this novel andrographolide-lipoic acid conjugate were investigated. Methods In alloxan-treated mice (a model of type 1 diabetes), drugs were administered orally once daily for 6 days post-alloxan treatment. Fasting blood glucose and serum insulin were determined. Pathologic and immunohistochemical analysis of pancreatic islets were performed. Translocation of glucose transporter subtype 4 in soleus muscle was detected by western blot. In RIN-m cells in vitro, the effect of AL-1 on H2O2-induced damage and reactive oxidative species production stimulated by high glucose and glibenclamide were measured. Inhibition of nuclear factor kappa B (NF-κB) activation induced by IL-1β and IFN-γ was investigated. Results In alloxan-induced diabetic mouse model, AL-1 lowered blood glucose, increased insulin and prevented loss of beta cells and their dysfunction, stimulated glucose transport protein subtype 4 (GLUT4) membrane translocation in soleus muscles. Pretreatment of RIN-m cells with AL-1 prevented H2O2-induced cellular damage, quenched glucose and glibenclamide-stimulated reactive oxidative species production, and inhibited cytokine-stimulated NF-κB activation. Conclusion We have demonstrated that AL-1 had both hypoglycemic and beta cell protective effects which translated into antioxidant and NF-κB inhibitory activity. AL-1 is a potential new anti-diabetic agent.

For texture control in plant-meat alternatives, the interrelationship between apparent characteristics and chemical bonds in high-fiber formulations remains unclear. The influence of mulberry leaf powder on apparent characteristics and chemical bonds of raw materials, block and strip products at addition amounts of 0.5-25% was analyzed. The results showed that 8% addition significantly increased the chewiness of the block by 98.12%. The strips' texture shows a downward trend, and the processing produced more redness and color difference. Additives promoted the formation of voids, lamellar and filamentous structures, and the strip produced more striped structures. Disulfide bonds significantly increased in the block, and the β-turn in the secondary structure enhanced by 12.20%. The β-turn transformed into a β-sheet in strips. Principal component analysis revealed that the texture improvement was associated with producing disulfide bonds and β-turn, providing a basis for high-fiber components to improve products' apparent characteristics by chemical bonds., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in the paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: The objective of this study was to investigate the senescent phenotypes of human corneal endothelial cells (hCEnCs) upon treatment with ultraviolet (UV)-A., Methods: We assessed cell morphology, senescence-associated β-galactosidase (SA-β-gal) activity, cell proliferation and expression of senescence markers ( p16 and p21 ) in hCEnCs exposed to UV-A radiation, and senescent hCEnCs induced by ionizing radiation (IR) were used as positive controls. We performed RNA sequencing and proteomics analyses to compare gene and protein expression profiles between UV-A- and IR-induced senescent hCEnCs, and we also compared the results to non-senescent hCEnCs., Results: Cells exposed to 5 J/cm2 of UV-A or to IR exhibited typical senescent phenotypes, including enlargement, increased SA-β-gal activity, decreased cell proliferation and elevated expression of p16 and p21 . RNA-Seq analysis revealed that 83.9% of the genes significantly upregulated and 82.6% of the genes significantly downregulated in UV-A-induced senescent hCEnCs overlapped with the genes regulated in IR-induced senescent hCEnCs. Proteomics also revealed that 93.8% of the proteins significantly upregulated in UV-A-induced senescent hCEnCs overlapped with those induced by IR. In proteomics analyses, senescent hCEnCs induced by UV-A exhibited elevated expression levels of several factors part of the senescence-associated secretory phenotype., Conclusions: In this study, where senescence was induced by UV-A, a more physiological stress for hCEnCs compared to IR, we determined that UV-A modulated the expression of many genes and proteins typically altered upon IR treatment, a more conventional method of senescence induction, even though UV-A also modulated specific pathways unrelated to IR.

Background: With the requirements of environmental, cost and economic sustainability, new sources of alternative proteins in the livestock industry are receiving increasing attention. Mulberry (Morus alba L.) leaves are a unique feed resource because of their high protein content and large availability. Therefore, mining sustainable protein suitable for the animal husbandry industry in sericulture resources could achieve a win-win situation., Results: The protein content in mulberry leaves is 232.10-386.16 g kg -1 , and the mean value of crude fat content is 43.76 ± 8.48 g kg -1 , which has the advantages of protein content and energy. In addition, the average content of phytic acid in mulberry leaves is only 1.88 ± 0.56 g kg -1 , which means that it is not inhibited in terms of nutrient absorption. Meanwhile, the digestibility of protein was Bean pulp > Sample 8 ≈ Alfalfa ≈ Sample 13 ≈ Cottonseed meal > Fish meal, and the β-turn and particle size of mulberry leaf protein are more conducive to digestion in vitro. Furthermore, the protein of Sample 13 had the richest essential amino acids (252.00 g kg -1 ) and the highest essential amino acid index (EAAI), which was superior to conventional feed protein. In addition, the partial substitution of mulberry leaf protein (15%) significantly increased the EAAI value of conventional feed protein. However, to balance nutrition, it is necessary to combine mulberry leaf protein with other proteins to further broaden its application field., Conclusion: Mulberry leaves are a new source of feed protein, which helps to alleviate the two major problems of mulberry resource surplus and feed protein resource shortage. © 2023 Society of Chemical Industry., (© 2023 Society of Chemical Industry.)

Background: The WUSCHEL-related Homeobox (WOX) genes, which encode plant-specific homeobox (HB) transcription factors, play crucial roles in regulating plant growth and development. However, the functions of WOX genes are little known in Eucalyptus, one of the fastest-growing tree resources with considerable widespread cultivation worldwide., Results: A total of nine WOX genes named EgWOX1-EgWOX9 were retrieved and designated from Eucalyptus grandis. From the three divided clades marked as Modern/WUS, Intermediate and Ancient, the largest group Modern/WUS (6 EgWOXs) contains a specific domain with 8 amino acids: TLQLFPLR. The collinearity, cis-regulatory elements, protein-protein interaction network and gene expression analysis reveal that the WUS proteins in E. grandis involve in regulating meristems development and regeneration. Furthermore, by externally adding of truncated peptides isolated from WUS specific domain, the transformation efficiency in E. urophylla × E. grandis DH32-29 was significant enhanced. The transcriptomics data further reveals that the use of small peptides activates metabolism pathways such as starch and sucrose metabolism, phenylpropanoid biosynthesis and flavonoid biosynthesis., Conclusions: Peptides isolated from WUS protein can be utilized to enhance the transformation efficiency in Eucalyptus, thereby contributing to the high-efficiency breeding of Eucalyptus., (© 2023. The Author(s).)

Background: Extrahepatic cholangiocarcinoma sarcoma is extremely rare in clinical practice. These cells consist of both epithelial and mesenchymal cells. Patient-derived cell lines that maintain tumor characteristics are valuable tools for studying the molecular mechanisms associated with carcinosarcoma. However, cholangiocarcinoma sarcoma cell lines are not available in cell banks., Aim: To establish and characterize a new extrahepatic cholangiocarcinoma sarcoma cell line, namely CBC2T-2., Methods: We conducted a short tandem repeat (STR) test to confirm the identity of the CBC2T-2 cell line. Furthermore, we assessed the migratory and invasive properties of the cells and performed clonogenicity assay to evaluate the ability of individual cells to form colonies. The tumorigenic potential of CBC2T-2 cells was tested in vivo using non-obese diabetic/severe combined immunodeficient (NOD/SCID) mice. The cells were injected subcutaneously and tumor formation was observed. In addition, immunohistochemical analysis was carried out to examine the expression of epithelial marker CK19 and mesenchymal marker vimentin in both CBC2T-2 cells and xenografts. The CBC2T-2 cell line was used to screen the potential therapeutic effects of various clinical agents in patients with cholangiocarcinoma sarcoma. Lastly, whole-exome sequencing was performed to identify genetic alterations and screen for somatic mutations in the CBC2T-2 cell line., Results: The STR test showed that there was no cross-contamination and the results were identical to those of the original tissue. The cells showed round or oval-shaped epithelioid cells and mesenchymal cells with spindle-shaped or elongated morphology. The cells exhibited a high proliferation ratio with a doubling time of 47.11 h. This cell line has migratory, invasive, and clonogenic abilities. The chromosomes in the CBC2T-2 cells were polyploidy, with numbers ranging from 69 to 79. The subcutaneous tumorigenic assay confirmed the in vivo tumorigenic ability of CBC2T-2 cells in NOD/SCID mice. CBC2T-2 cells and xenografts were positive for both the epithelial marker, CK19, and the mesenchymal marker, vimentin. These results suggest that CBC2T-2 cells may have both epithelial and mesenchymal characteristics. The cells were also used to screen clinical agents in patients with cholangiocarcinoma sarcoma, and a combination of paclitaxel and gemcitabine was found to be the most effective treatment option., Conclusion: We established the first human cholangiocarcinoma sarcoma cell line, CBC2T-2, with stable biogenetic traits. This cell line, as a research model, has a high clinical value and would facilitate the understanding of the pathogenesis of cholangiocarcinoma sarcoma., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Purpose: This study aimed to investigate the senescent phenotypes of human corneal and conjunctival epithelial cells., Methods: We examined cell morphology, senescence-associated β-galactosidase (SA-β-gal) activity, cell proliferation, and expression of senescence markers (p16 and p21). RNA sequencing analysis was conducted to compare gene expression profiles between senescent and non-senescent cells. Finally, the potential involvement of senescent cells in the pathogenesis of ocular surface diseases was investigated., Results: X-irradiated corneal and conjunctival epithelial cells exhibited typical senescence phenotypes, i.e., flattened morphologies, increased SA-β-gal activity, decreased cell proliferation, and increased expression of senescence markers, p16 and p21. RNA-seq analysis revealed substantial differences in gene expression profiles between senescent corneal (SCo) and conjunctival epithelial cells (SCj). Moreover, SCj were detected in pathological conjunctival tissues associated with limbal stem cell deficiency (LSCD) due to Stevens-Johnson syndrome or chemical burns, potentially being involved in abnormal differentiation., Conclusion: This study highlights the cellular and molecular characteristics of senescent ocular surface cells, particularly in SCj that show abnormal keratin expression, and their potential roles in severe ocular surface diseases and pathology.

Sorting behaviour is a common phenomenon observed in ruminants when they are provided with a total mixed ration, which contributes to variations in the severity of subacute ruminal acidosis (SARA). Pelleted total mixed ration (PTMR) reduces sorting, but high-grain content increases acidosis risk. However, whether the variability in the severity of SARA exists in sheep fed the same high-grain PTMR is less understood. This study aimed to investigate SARA variability among individual sheep offered a high-grain PTMR, considering chewing activity, ruminal fermentation, bacterial communities and nutrient digestibility. Twenty ruminally cannulated male Hu sheep were individually housed in cages and fed a PTMR comprising 80% concentrate mix and 20% roughage. A 14-day adaptation period to the diet and facilities was provided before a 10-day sample collection period. Continuous monitoring of ruminal pH was conducted for 48 h, during which time chewing activity was also recorded. Ruminal fluid samples were collected for analysis of volatile fatty acid and microbial DNA extraction. Faecal samples were collected to measure nutrient digestibility. Based on their acidosis index, the sheep were classified into two groups: SARA-susceptible group (n = 6) and SARA-tolerant group (n = 6). The SARA-susceptible sheep exhibited a lower ruminal mean pH and minimum pH than the SARA-tolerant sheep (P < 0.05). Additionally, the SARA-susceptible group increased the acidosis index, duration and areas of pH below 5.8 and 5.6 compared to the SARA-tolerant group (P < 0.05). The SARA-susceptible group also exhibited a longer ruminating time than the SARA-tolerant group (P < 0.05). The SARA-susceptible group exhibited a tendency to increase the relative abundance of Firmicutes (P = 0.089), while simultaneously decreasing the copy number of Fibrobacter succinogenes in the rumen, as well as the digestibility of NDF and ADF compared to the SARA-tolerant group (P < 0.05). The acidosis index was found to be positively correlated with ruminating time (min/kg DM intake (DMI)) and total chewing time (min/kg DMI), but negatively correlated with the copy number of Fibrobacter succinogenes and Ruminococcus albus in the rumen. These findings indicate that there exists variability in the SARA severity among sheep when fed a high-grain PTMR, as evidenced by varied chewing activity, bacterial communities and nutrient digestibility. Ruminating time, total chewing time per kilogram of DMI as well as the copy number of Fibrobacter succinogenes and Ruminococcus albus in the rumen hold potential as indicators for assessing the severity of SARA., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

The global distribution of microplastics (MPs) across various environmental compartments has garnered significant attention. However, the differences in the characteristics of MPs in different environments remain unclear, and there is still a lack of quantitative analysis of their environmental sources. In addition, the inclusion of aging in source apportionment is a novel approach that has not been widely explored. In this study, we conducted a meta-analysis of the literature from the past 10 years and extracted conventional and aging characteristic data of MPs from 321 sampling points across 7 environmental compartments worldwide. We established a data-driven analysis framework using these data sets to identify different MP communities across environmental compartments, screen key MP features, and develop an environmental source analysis model for MPs. Our results indicate significant differences in the characteristics of MP communities across environments. The key features of differentiation were identified using the LEfSe method and include the carbonyl index, hydroxyl index, fouling index, proportions of polypropylene, white, black/gray, and film/sheet. These features were screened for each environmental compartment. An environmental source identification model was established based on these features with an accuracy of 75.1%. In order to accurately represent the single/multisource case in a more probabilistic manner, we proposed the MP environmental source index (MESI) to provide a probability estimation of the sample having multiple sources. Our findings contribute to a better understanding of MP migration trends and fluxes in the plastic cycle and inform effective prevention and control strategies for MP pollution.

In contrast to a plethora of macrocyclic and cage compounds, spirophanes have remained largely unexplored. We report herein the construction, structure and properties of unprecedented tetrahomo corona[4]arene-based ditopic and tritopic macrocycles of spiro structures. Synthesis was conveniently achieved by means of an efficient S N Ar reaction from simple and commercially available starting materials. Racemic samples were resolved into enantiopure chiral tetrahomo i -corona[4]arenes, spirophanes and bispirophanes which show interesting chiroptical properties. The acquired electron-deficient macrocyclic compounds were found to adopt unique conformational structures and to form distinct complexes with TTF in the solid state. Our study provides a new opportunity to develop multitopic macrocycles of different topologies which have potential applications in supramolecular chemistry., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Agrobacterium rhizogenes is a soil bacteria with extensive infectivity, which can infect almost all dicotyledonous plants and a few monocotyledonous plants to induce root nodules. This is caused by the root-inducing plasmid, which contains genes responsible for the autonomous growth of root nodules and crown gall base synthesis. Structurally, it is similar to the tumor-inducing plasmid in that it mainly contains the Vir region, the T-DNA region, and the functional region of crown gall base synthesis. Its T-DNA is integrated into the nuclear genome of the plant with the assistance of Vir genes, causing hairy root disease in the host plant and the formation of hairy roots. The roots produced by Agrobacterium rhizogenes -infested plants are characterized by a fast growth rate, high degree of differentiation, physiological, biochemical, and genetic stability, and ease of manipulation and control. In particular, the hairy root system is an efficient and rapid research tool for plants that have no affinity for transformation by Agrobacterium rhizogenes and low transformation efficiency. The establishment of germinating root culture system for the production of secondary metabolites in the original plants through the genetic transformation of natural plants mediated by root-inducing plasmid in Agrobacterium rhizogenes has become a new technology combining plant genetic engineering and cell engineering. It has been widely used in a variety of plants for different molecular purposes, such as pathological analysis, gene function verification, and secondary metabolite research. Chimeric plants obtained by induction of Agrobacterium rhizogenes that can be expressed instantaneously and contemporarily are more rapidly obtained, compared to tissue culture and stably inheritable transgenic strains. In general, transgenic plants can be obtained in approximately one month., Competing Interests: Competing interestsThere are no conflicts of interest or competing interests., (Copyright © 2023 The Authors; exclusive licensee Bio-protocol LLC.)

Background: The antioxidant properties of active peptides from silkworm pupae protein hydrolysate are of interest, and it serves as a novel source of calcium supplement., Methods: Optimize the preparation parameters of silkworm pupae bioactive peptide-calcium chelate, and investigate the mechanism and bioavailability of silkworm pupae active peptide as a transport carrier to promote calcium ion absorption using simulated gastrointestinal digestion and Caco-2 monolayer cell model., Results: The optimal process parameters for preparing peptide calcium chelate were the peptide calcium mass ratio of 3:1, pH of 6.7, a temperature of 35.6°C, and time of 32.8 min by Box-Behnken design, and the calciumchelating rate reached 84.67%. The DPPH radical scavenging activity of silkworm pupae protein hydrolysatecalcium chelate was 79.36 ± 4.31%, significantly higher than silkworm pupae protein hydrolysate (61.00 ± 9.56%). Fourier transform infrared spectroscopy shows that the COO-, N-H, C-H, and C-O groups participated in the formation of silkworm pupae protein hydrolysate-calcium chelate. The particle size of the silkworm pupae protein hydrolysate-calcium chelate was 970.75 ± 30.12 nm, which was significantly higher than that of silkworm pupae protein hydrolysate (253.14 ± 5.72 nm). The silkworm pupae protein hydrolysate-calcium chelate showed a calcium dissolution rate of 71.01 ± 1.91% in the simulated intestinal phase, significantly higher than that of CaCl2 (59.34 ± 1.24%). In the Caco-2 cell monolayers, the silkworm pupae protein hydrolysatecalcium chelate was more favorable for calcium transport., Conclusion: A novel silkworm pupa protein hydrolysate-calcium chelate with high antioxidant activity was successfully prepared to improve the bioavailability of calcium., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The earth land area is heterogeneous in terms of elevation; about 45% of its land area belongs to higher elevation with altitude above 500 meters compared to sea level. In most cases, oxygen concentration decreases as altitude increases. Thus, high-altitude hypoxic stress is commonly faced by residents in areas with an average elevation exceeding 2500 meters and those who have just entered the plateau. High-altitude hypoxia significantly affects advanced neurobehaviors including learning and memory (L&M). Hippocampus, the integration center of L&M, could be the most crucial target affected by high-altitude hypoxia exposure. Based on these points, this review thoroughly discussed the relationship between high-altitude hypoxia and L&M impairment, in terms of hippocampal neuron apoptosis and dysfunction, neuronal oxidative stress disorder, neurotransmitters and related receptors, and nerve cell energy metabolism disorder, which is of great significance to find potential targets for medical intervention. Studies illustrate that the mechanism of L&M damaged by high-altitude hypoxia should be further investigated based on the entire review of issues related to this topic., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2022 Zi-ang Zhang et al.)

With continuous development of pesticide dosage forms, emulsifiable concentrates using large amounts of organic solvents are gradually obsoleted. Nanoemulsions with high water content have been developed and the preparation processes also evolved, but these processes still exist some problems, such as poor controllability and high energy consumption. Microfluidic is a controllable nanoemulsion preparation system which mainly applied to pharmaceutical synthesis. In this study, the pesticide phoxim nanoemulsion was prepared by microfluidic technology. The optimized formulation of phoxim nanoemulsion was composed of Tween 80 and pesticide emulsifier 500 as surfactant, hexyl acetate as oil, and n-propanol as co-surfactant. Moreover, when the flow rates of water and oil in the microfluidic system were adjusted to 5 μL/min and 20 μL/min, phoxim nanoemulsion was obtained with a cloud point/boiling point of 109 °C, a particle size of 21.5 ± 0.8 nm and a potential value of - 18.7 ± 0.6 mV. Furthermore, the nanoemulsion had a rapid release effect in vitro which could be fitted by the Ritger-Peppas model. The feeding toxicity of the phoxim nanoemulsion was higher than that of commercial formulation while the contact killing effect was higher than that of the active ingredient. Therefore, pesticide dosage was reduced and the insecticidal effect was enhanced by using phoxim nanoemulsions. These results also confirm the potential of microfluidics as a green process to produce pesticide nanoemulsions., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The interactions between nanoparticles (NPs) and plasma proteins form a protein corona around NPs after entering the biological environment, which provides new biological properties to NPs and mediates their interactions with cells and biological barriers. Given the inevitable interactions, we regard nanoparticle‒protein interactions as a tool for designing protein corona-mediated drug delivery systems. Herein, we demonstrate the successful application of protein corona-mediated brain-targeted nanomicelles in the treatment of glioma, loading them with paclitaxel (PTX), and decorating them with amyloid β-protein (Aβ)-CN peptide (PTX/Aβ-CN-PMs). Aβ-CN peptide, like the Aβ 1-42 peptide, specifically binds to the lipid-binding domain of apolipoprotein E (ApoE) in vivo to form the ApoE-enriched protein corona surrounding Aβ-CN-PMs (ApoE/PTX/Aβ-CN-PMs). The receptor-binding domain of the ApoE then combines with low-density lipoprotein receptor (LDLr) and LDLr-related protein 1 receptor (LRP1r) expressed in the blood-brain barrier and glioma, effectively mediating brain-targeted delivery., Methods: PTX/Aβ-CN-PMs were prepared using a film hydration method with sonication, which was simple and feasible. The specific formation of the ApoE-enriched protein corona around nanoparticles was characterized by Western blotting analysis and LC-MS/MS. The in vitro physicochemical properties and in vivo anti-glioma effects of PTX/Aβ-CN-PMs were also well studied., Results: The average size and zeta potential of PTX/Aβ-CN-PMs and ApoE/PTX/Aβ-CN-PMs were 103.1 nm, 172.3 nm, 7.23 mV, and 0.715 mV, respectively. PTX was efficiently loaded into PTX/Aβ-CN-PMs, and the PTX release from rhApoE/PTX/Aβ-CN-PMs exhibited a sustained-release pattern in vitro. The formation of the ApoE-enriched protein corona significantly improved the cellular uptake of Aβ-CN-PMs on C6 cells and human umbilical vein endothelial cells (HUVECs) and enhanced permeability to the blood-brain tumor barrier in vitro. Meanwhile, PTX/Aβ-CN-PMs with ApoE-enriched protein corona had a greater ability to inhibit cell proliferation and induce cell apoptosis than taxol. Importantly, PTX/Aβ-CN-PMs exhibited better anti-glioma effects and tissue distribution profile with rapid accumulation in glioma tissues in vivo and prolonged median survival of glioma-bearing mice compared to those associated with PMs without the ApoE protein corona., Conclusions: The designed PTX/Aβ-CN-PMs exhibited significantly enhanced anti-glioma efficacy. Importantly, this study provided a strategy for the rational design of a protein corona-based brain-targeted drug delivery system. More crucially, we utilized the unfavorable side of the protein corona and converted it into an advantage to achieve brain-targeted drug delivery., (© 2021. The Author(s).)

Objective : This study aimed to elucidate the pharmacological effects of sesamin (Ses) and its mechanism of action towards PM 2.5 -induced cardiovascular injuries. Method : Forty Sprague Dawley (SD) rats were randomly divided into five groups: a saline control group; a PM 2.5 exposure group; and low-, middle-, and high-dose Ses pretreatment groups. The SD rats were pretreated with different concentrations of Ses for 21 days. Afterward, the rats were exposed to ambient PM 2.5 by intratracheal instillation every other day for a total of three times. The levels of inflammatory markers, including tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β), and interleukin-6 (IL-6), and indicators related to oxidative responses, such as total superoxide dismutase (SOD), reduced glutathione (GSH), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA), were measured in the blood and heart. The expression of ferroptosis-related proteins in heart tissues was determined via western blot and immunohistochemistry. Results : Ses pretreatment substantially ameliorated cardiovascular injuries in rats as evidenced by the decrease in the pathological score and collagen area. The decreased levels of SOD, GSH, and GSH-Px in the heart and serum were inhibited by Ses. In addition, Ses not only notably increased the activity of antioxidant enzymes but also reduced the levels of MDA, CK, LDH, CK-MB, IL-6, TNF-α, IL-1β, and IL-6. Furthermore, Ses pretreatment upregulated the expression levels of GPX4, SLC7A11, TFRC, and FPN1 and inhibited the expression levels of FTH1 and FTL. Conclusion : Ses pretreatment could ameliorate PM 2.5 -induced cardiovascular injuries perhaps by inhibiting ferroptosis. Therefore, Ses pretreatment may be a novel strategy for the prevention and treatment of PM 2.5 -induced cardiovascular injury.

Aristolochic acid I (AAI) is a well-known nephrotoxic carcinogen, which is currently reported to be also associated with hepatocellular carcinoma (HCC). Whether AAI is a direct hepatocarcinogen remains controversial. In this study we investigated the association between AAI exposure and HCC in adult rats using a sensitive rat liver bioassay with several cofactors. Formation of glutathione S-transferase placental form-positive (GST-P + ) foci was used as the marker for preneoplastic lesions/clonal expansion. We first conducted a medium-term (8 weeks) study to investigate whether AAI had any tumor-initiating or -promoting activity. Then a long-term (52 weeks) study was conducted to determine whether AAI can directly induce HCC. We showed that oral administration of single dose of AAI (20, 50, or 100 mg/kg) in combination with partial hepatectomy (PH) to stimulate liver proliferation did not induce typical GST-P + foci in liver. In the 8-week study, only high dose of AAI (10 mg · kg -1  · d -1 , 5 days a week for 6 weeks) in combination with PH significantly increased the number and area of GST-P + foci initiated by diethylnitrosamine (DEN) in liver. Similarly, only high dose of AAI (10 mg· kg -1 · d -1 , 5 days a week for 52 weeks) in combination with PH significantly increased the number and area of hepatic GST-P + foci in the 52-week study. No any nodules or HCC were observed in liver of any AAI-treated groups. In contrast, long-term administration of AAI (0.1, 1, 10 mg· kg -1 · d -1 ) time- and dose-dependently caused death due to the occurrence of cancers in the forestomach, intestine, and/or kidney. Besides, AAI-DNA adducts accumulated in the forestomach, kidney, and liver in a time- and dose-dependent manner. Taken together, AAI promotes clonal expansion only in the high-dose group but did not induce any nodules or HCC in liver of adult rats till their deaths caused by cancers developed in the forestomach, intestine, and/or kidney. Findings from our animal studies will pave the way for further large-scale epidemiological investigation of the associations between AA and HCC., (© 2021. The Author(s), under exclusive licence to CPS and SIMM.)

Ovarian cancer (OC) is the leading cause of cancer-related death among all gynecological tumors. N6-methyladenosine (m6A)-related regulators play essential roles in various tumors, including OC. However, the expression of m6A RNA methylation regulators and the related regulatory network in OC and their correlations with prognosis remain largely unknown. In the current study, we obtained the genome datasets of OC from GDC and GTEx database and analyzed the mRNA levels of 21 key m6A regulators in OC and normal human ovarian tissues. The expression levels of 7 m6A regulators were lower in both the OC tissues and the high-stage group. Notably, the 5-year survival rate of patients with OC presenting low VIRMA expression or high HNRNPA2B1 expression was higher than that of the controls. Next, a risk score model based on the three selected m6A regulators (VIRMA, IGF2BP1, and HNRNPA2B1) was built by performing a LASSO regression analysis, and the moderate accuracy of the risk score model to predict the prognosis of patients with OC was examined by performing ROC curve, nomogram, and univariate and multivariate Cox regression analyses. In addition, a regulatory network of miRNAs-m6A regulators-m6A target genes, including 2 miRNAs, 3 m6A regulators, and 47 mRNAs, was constructed, and one of the pathways, namely, miR-196b-5p-IGF2BP1-PTEN, was initially validated based on bioinformatic analysis and assay verification. These results demonstrated that the risk score model composed of three m6A RNA methylation regulators and the related network of miRNAs-m6A regulators-m6A target genes is valuable for predicting the prognosis of patients with OC, and these molecules may serve as potential biomarkers or therapeutic targets in the future., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Li, Ren, Chen, Yang, Zhang, Wang, Zhu, Li, Yang and Zhang.)

Objective: To compare the postoperative inflammation and pain response between medial pivot (MP) and posterior stabilized (PS) prostheses among total knee arthroplasty (TKA) patients., Methods: A prospective cohort study was conducted from January 2019 to May 2019 at the Affiliated Hospital of Qingdao University. The study included patients diagnosed with stage III or IV Kellgren-Lawrence knee osteoarthritis (KOA) who had failed conservative treatment, had undergone no previous knee surgeries, had varus substantial deformities (11°-20° deviation), and had received their first unilateral TKA. A total of 109 patients who underwent PS prosthesis TKA and 98 patients who underwent MP prosthesis TKA were continuously enrolled. Inflammation biomarkers, such as leukocyte (white blood cells), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP), together with hemoglobin (Hb), the visual analog pain score (VAS) and range of motion (ROM) were compared between the two groups. The Student t-test was applied to analyze continuous parameters, and the χ 2 -test was used for categorical parameters. The linear mixed model was used for the repeated measurement data from the follow-up visits. Multivariate backward logistic and linear regression models were used to determine the factors potentially influencing prostheses and VAS scores., Results: All these enrolled patients were followed up at 2, 4, 7, and 30 days after TKA. There were no significant differences between the PS group and the MP group in body mass index (BMI), gender, laterality, usage of nonsteroidal anti-inflammatory drugs (NSAIDs) and opioids, and drain tube extubation time (P > 0.05). Compared with the PS group, the MP group were older (67.5 years vs 65.4 years), and had a higher mid-vastus approach rate (67.3% vs 26.6%), a shorter tourniquet duration (68.3 ± 10.2 h vs 73.9 ± 11.2 h), a larger prosthetic pad (10.8 ± 1.2 mm vs 10.4 ± 1.2 mm), and a lower drain tube diversion volume (187.6 ± 119.3 mL vs 234.0 ± 155.7 mL). In the linear mixed model, MP prostheses had less CRP and ESR elevation and less Hb decrease than PS prostheses (P for group × time < 0.001). There were no significant differences in the changing trends between MP and PS prostheses by time for VAS scores and ROM. In the multivariate logistic regression model, MP prostheses showed significant differences compared with PS prostheses in treatment approach (odds ratio [OR] = 3.371, 95% confidence interval [CI]: 1.953-7.127; P < 0.001), ultrasound treatment start time (OR = 2.669, 95% CI: 1.385-5.141; P = 0.003), and tourniquet duration (OR = 0.954, 95% CI: 0.925-0.984; P = 0.003). Higher VAS scores on the second day postoperatively were related to high VAS scores preoperatively, use of opioids, high drain tube diversion, long tourniquet duration, and long drain tube extubation (P < 0.05), respectively., Conclusion: The MP prostheses showed potential advantages compared with PS prostheses in TKA in inflammatory responses., (© 2020 The Authors. Orthopaedic Surgery published by Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.)

The aim of the present study was to investigate the differences of the pathological changes and cognitive function after bilateral common carotid artery occlusion (BCCAO) between Sprague-Dawley (SD) and Wistar rats. Male SD and Wistar rats were randomly divided into 2 groups, respectively: sham operated (S-sham and W-sham) and operated (S-BCCAO and W-BCCAO) groups. The survival rate and the rate of loss of pupillary light reflex (PLR) were observed on day 1, 3, 7, 14 and 28 after the operation, and the light-dark box, Y-maze and odor recognition tests were performed to detect cognitive function on day 28 after the operation. HE and Luxol fast blue staining were used to observe the pathological changes of gray matter (hippocampus), white matter (optical tract), optic nerve, and retina. The results showed that the survival rate of the W-BCCAO group was 62.5%, and PLR loss rate was 100%; whereas the survival rate of the S-BCCAO group was 100%, and PLR loss rate was 58.3%. In the W-BCCAO group, percentages of time spent and distance traveled in the light box were more than those in the W-sham group, but there was no statistical significance between the S-BCCAO and S-sham groups. In the S-BCCAO group, the percentages of time spent and distance traveled in the III arm (labyrinth arm) of the Y-maze were less than those in the S-sham group, but no statistical significance was found between the W-BCCAO group and W-sham group. In the S-BCCAO group, the discrimination ratio of the odor recognition task was less than that in the S-sham group, but no statistical significance could be seen between the W-BCCAO and W-sham groups. Ischemic injury was observed in the CA1 area of the hippocampus in the S-BCCAO group, but no readily visible damage was observed in the W-BCCAO group. Ischemic injury of the visual beam and optic nerve was observed in both the S-BCCAO and W-BCCAO groups. Compared with the corresponding sham groups, the S-BCCAO and W-BCCAO groups showed serious retinal damage with significant thinner retina. The ganglion cell layer (GCL), inner plexiform layer (IPL), and outer plexiform layer (OPL) were thinner in the S-BCCAO group, but no statistical significances were shown in the other layers. All the layers, except the outer nuclear layer (ONL), were significantly thinner in the W-BCCAO group. The results indicate that there are differences of the pathological changes in the hippocampus and visual conduction pathway after BCCAO between SD and Wistar rats, and the degree of learning and memory injury was also different, which suggests that the vascular dementia model of different rat strains should be selected according to research purpose.

Competing Interests: Competing interests: None declared.

Competing Interests: Competing interests: None declared.

Aristolochic acid I (AAI) derived from a natural herbal alkaloid is a nephrotoxicant. AAI-induced acute kidney injury (AKI), a devastating clinical disease associated with high mortality rates, is difficult for early diagnosis. To address this issue, we identified and validated early-detection biomarkers for AAI-induced acute kidney injury via profiling microRNA expression in rats. Global miRNA expression profile analysis found that 21 miRNAs were significantly dysregulated in kidney of rats treated by 40 mg/kg AAI on day 2, day 4, or day 6, among which 5 miRNAs were upregulated at all three time points. Quantitative RT-PCR confirmed that miR-21-3p on day 4 and day 6 was obviously upregulated in kidney of rats treated by 40 mg/kg AAI. Further examination found that miR-21-3p was increased in plasma early on day 2 in 10 mg/kg AAI-treated rats, but not in non-target organs. Importantly, the elevation of plasma miR-21-3p preceded the increase in blood urea nitrogen and creatinine, and the presence of renal tubular injury, characterized by differential increase before and after the presence of renal tubular lesions. Our findings thus show that miRNA expression is upregulated in kidney and plasma of AKI rat induced by AAI, and plasma miR-21-3p may be served as a new potential biomarker for early diagnosing AAI-induced acute kidney injury in rats, and possibly in humans.

Many Aristolochia species herbal drugs, used for diseases treatment since antiquity, contain active component aristolochic acid mixture, which consists of aristolochic acid I and II. However, it remains unclear whether aristolochic acid I is gastrotoxic, though evidence has shown that aristolochic acid mixture is nephrotoxic, carcinogenic, and genotoxic. The present study aimed to investigate the gastrotoxicity in rats treated with aristolochic acid I alone. Four groups of rats were orally administrated with vehicle (1% NaHCO3), or 30mg, 60mg, and 90mg/kg/day of aristolochic acid I for twelve days. The results showed that aristolochic acid I can induce obvious body weight loss, forestomach injury characterized by necrosis, ulcer, hyperkeratosis, and hyperplasia of epithelial cells. The severity of these forestomach lesions was presented in a dose-dependent mode. Meanwhile, only non-specific, slight renal tubule degeneration, and occasionally single necrotic epithelial cell were found in aristolochic acid I-treated rats' kidney. These resulst indicated aristolochic acid I had obvious gastrotoxicity, and such aristolochic acid I-induced forestomach toxicity probably presented much prior to kidney injury. Such irritation lesions may play a partial role in gastric cancer development of rats induced by aristolochic acid. Therefore, these results expanded our understanding on the digestive system toxicity of aristolochic acid I., (Copyright © 2016 Elsevier GmbH. All rights reserved.)

Objective: To investigate the differences between emergency surgery and selective surgery treatment of ankle fractures with dislocation., Methods: In the study, 40 patients with ankle fracture and dislocation were treated and followed up from May 2013 to May 2014, and all the data were collected and analyzed. The subjects involved 29 male patients and 11 female patients. The patients were randomly separated into two groups, and the patients in group A were given surgical intervention within 6 hours after injury, while those in group B were initially given close reduction and given selective operation when the soft tissue condition got better. Group A contained 13 male patients and 7 female patients with average age of 37.10; Group B consisted of 15 male and 5 female, with average age of 37.85., Results: The Baird-Jackson score was applied for assessment of the patients' outcomes. According to the score, the outcomes were classified into excellent, good, fair, and poor. In group A (emergency group), the outcomes were 13 (65.0%), 4 (20.0%), 3 (15.0%), and 0, respectively. In group B (selective group), they were 11 (55.0%), 7 (35.0%), 2 (10.0%), and 0, respectively. The numbers of the patients from excellent to poor were 24 (55.0%), 11 (27.5%), 5 (12.5%), and 0, respectively., Conclusion: There is no significant difference in postoperative function between the two groups, however, early surgical intervention can benefit in accomplishing anatomical reduction much easier and shortening the time of hospitalization, which is cost-saving for the patients.

Pregnancy-related pelvic ring disease brings great suffering to pregnant women, including the separation of the pubic symphysis and sacroiliac joint pain. Hormonal changes leading to ligamentous laxity is the main reason for Pregnancy-related pelvic ring disease. In normal pregnant cases, and the physiologic widening at the symphysis is about 3-7 mm. When the widening of the symphysis is more than 10 mm, it may lead to symptoms and need active treatment. Currently the diagnosis of the pubic symphysis separation is based on the clinical symptoms and signs. The treatment of acute pubic symphysis separation bases on conservative therapy, includes bed rest and physical therapy. But when the widening of the symphysis is more than 4 cm, the surgery intervention may be a good treatment. If the conservative treatment is not obviously effective, the surgery consists of plate fixation in the pubic symphysis and sacroiliac screw fixation. Other indications for the surgical intervention include inadequate reduction, recurrent diastasis, intractable symptoms, and open rupture.

Background: Old pelvis fractures are among the most challenging fractures to treat because of their complex anatomy, difficult-to-access surgical sites, and the relatively low incidence of such cases. Proper evaluation and surgical planning are necessary to achieve the pelvic ring symmetry and stable fixation of the fracture. The goal of this study was to assess the use of three-dimensional (3D) printing techniques for surgical management of old pelvic fractures., Methods: First, 16 dried human cadaveric pelvises were used to confirm the anatomical accuracy of the 3D models printed based on radiographic data. Next, nine clinical cases between January 2009 and April 2013 were used to evaluate the surgical reconstruction based on the 3D printed models. The pelvic injuries were all type C, and the average time from injury to reconstruction was 11 weeks (range: 8-17 weeks). The workflow consisted of: (1) Printing patient-specific bone models based on preoperative computed tomography (CT) scans, (2) virtual fracture reduction using the printed 3D anatomic template, (3) virtual fracture fixation using Kirschner wires, and (4) preoperatively measuring the osteotomy and implant position relative to landmarks using the virtually defined deformation. These models aided communication between surgical team members during the procedure. This technique was validated by comparing the preoperative planning to the intraoperative procedure., Results: The accuracy of the 3D printed models was within specification. Production of a model from standard CT DICOM data took 7 hours (range: 6-9 hours). Preoperative planning using the 3D printed models was feasible in all cases. Good correlation was found between the preoperative planning and postoperative follow-up X-ray in all nine cases. The patients were followed for 3-29 months (median: 5 months). The fracture healing time was 9-17 weeks (mean: 10 weeks). No delayed incision healing, wound infection, or nonunions occurred. The results were excellent in two cases, good in five, and poor in two based on the Majeed score., Conclusions: The 3D printing planning technique for pelvic surgery was successfully integrated into a clinical workflow to improve patient-specific preoperative planning by providing a visual and haptic model of the injury and allowing patient-specific adaptation of each osteosynthesis implant to the virtually reduced pelvis.