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The interaction between tumor fatty acid metabolism and immune microenvironment is a novel topic in oncology research, and the relationship of lipid-derived factors with immune editing in tumor is unclear. The breast cancer samples from the TCGA database were used as the training set, and samples from GSE42568 were employed as the validation set for constructing a model to identify a signature associated with fatty acid metabolism through Lasso Cox regression. And the changes in immune related signatures and risk score before and after anti-PD-1 monotherapy were caught by the differential analysis in GSE225078. A 14-gene prognostic risk scoring model identifying by fatty acid metabolism relevant signature was conducted, and the high risk group had shorter overall survival and progression free survival than low risk group. Many metabolism-related pathways were enriched in the high risk group, and many immune-related pathways were enriched in low risk group. The crucial differentially expressed genes between the high/low risk groups, CYP4F8 and CD52, were found to be strongly associated with SUCLA2 and ACOT4 of 14-gene model, and strongly related to immune infiltration. Immune related signatures, fatty acid metabolism-risk score and the expression level of ALDH1A1 (in 14-gene-model) changed after anti-PD-1 monotherapy. And the mice model results also showed anti-PD-1 mAb could significantly reduce the expression level of ALDH1A1 (p < 0.01). These results brought up the crosstalk between immune components and fatty acid metabolism in breast cancer microenvironment, which provided a new possibility of targeting fatty acid metabolism for combination therapy in breast cancer immunotherapy.

Objective: The study analyzed the impact of urbanization on epidemiological characteristics of respiratory infectious disease in Tongzhou District, Beijing during 2014–2022 to provide reference for prevention and control priorities of respiratory infectious diseases during the innovative urbanization process in China. Methods: The incidence data of notifiable respiratory infectious diseases (NRIDs) in Tongzhou Beijing during 2014–2022 were summarized. The trend of incidence rate was analyzed by Joinpoint regression model, and entropy method was performed to construct the comprehensive index of urbanization (CIU) and generalized linear model was used to analyze the influence of CIU on the incidence rate of respiratory infectious diseases. Results: Totally 72616 NRIDs cases were reported in Tongzhou District during 2014–2022, and the incidence rate of NRIDs was higher during 2017–2019 (153/100 000) than during 2014–2016 (930/100 000) and during 2020–2022 (371/100 000), respectively (both P

Summary: The co-culture of two adult human colorectal cancer cell lines, Caco-2 and HT29, on Transwell is commonly used as an in vitro gut mimic, yet the translatability of insights from such a system to adult human physiological contexts is not fully characterized. Here, we used single-cell RNA sequencing on the co-culture to obtain a detailed survey of cell type heterogeneity in the system and conducted a holistic comparison with human physiology. We identified the intestinal stem cell-, transit amplifying-, enterocyte-, goblet cell-, and enteroendocrine-like cells in the system. In general, the co-culture was fetal intestine-like, with less variety of gene expression compared to the adult human gut. Transporters for major types of nutrients were found in the majority of the enterocytes-like cells in the system. TLR 4 was not expressed in the sample, indicating that the co-culture model is incapable of mimicking the innate immune aspect of the human epithelium.

ABSTRACT: Wenchang chicken, a prized local breed in Hainan Province of China renowned for its exceptional adaptability to tropical environments and good meat quality, is deeply favored by the public. However, an insufficient understanding of its population architecture and the unclear genetic basis that governs its typical attributes have posed challenges in the protection and breeding of this precious breed. To address these gaps, we conducted whole-genome resequencing on 200 Wenchang chicken samples derived from 10 distinct strains, and we gathered data on an array of 21 phenotype traits. Population genomics analysis unveiled distinctive population structures in Wenchang chickens, primarily attributed to strong artificial selection for different feather colors. Selection sweep analysis identified a group of candidate genes, including PCDH9, DPF3, CDIN1, and SUGCT, closely linked to adaptations that enhance resilience in tropical island habitats. Genome-wide association studies (GWAS) highlighted potential candidate genes associated with diverse feather color traits, encompassing TYR, RAB38, TRPM1, GABARAPL2, CDH1, ZMIZ1, LYST, MC1R, and SASH1. Through the comprehensive analysis of high-quality genomic and phenotypic data across diverse Wenchang chicken resource groups, this study unveils the intricate genetic backgrounds and population structures of Wenchang chickens. Additionally, it identifies multiple candidate genes linked to environmental adaptation, feather color variations, and production traits. These insights not only provide genetic reference for the purification and breeding of Wenchang chickens but also broaden our understanding of the genetic basis of phenotypic diversity in chickens.

Background: To meet the growing global demand for rehabilitation services, the World Health Organization (WHO) launched Rehabilitation 2030. This study was commissioned by the WHO to investigate the integration degree of traditional Chinese medicine (TCM) in Chinese health system rehabilitation services and the demand for TCM rehabilitation in China. Methods: Twenty TCM rehabilitation experts and relevant government administrators were invited to complete the questionnaire between September 2019 and January 2022. The development of traditional, complementary, and integrative medicine (TCI) rehabilitation in China was assessed primarily based on six different health system components. Results: 26 policies, regulations, and national strategic plans related to TCI rehabilitation were issued by relevant government departments since 2002; notably, 14 policies related to TCI rehabilitation development were intensively introduced from 2016 to 2021. These policies cover the three main areas of financing, infrastructure development, and service delivery. The National Administration of Traditional Chinese Medicine's investment in TCM clinical capacity infrastructure and scientific research in 2019–2021 increased by 66% compared to 2010–2012, and the average number of TCM hospitals with rehabilitation departments in 2020 increased by 6.5% compared to 2018. The proportion of community health service centers providing TCM services in primary medical and health institutions has increased by 30.8% over the past 10 years. Conclusion: Long-term continuous policies, substantial financial investment, and expansion of the scope of TCI rehabilitation services in primary care institutions have effectively contributed to the rapid development of TCI rehabilitation. However, human resources and financing mechanisms for TCI rehabilitation need further improvement.

Salvianolic acid A (SAA) is a traditional Chinese medicine that has a good therapeutic effect on cardiovascular disease. However, the underlying mechanisms by which SAA improves mitochondrial respiration and cardiac function in diabetic cardiomyopathy (DCM) remain unknown. This study aims to elucidate whether SAA had any cardiovascular protection on the pathophysiology of DCM and explored the potential mechanisms. Diabetes was induced in rats by 30 mg/kg of streptozotocin (STZ) treatment. After a week of stability, 5 mg/kg isoprenaline (ISO) was injected into the rats subcutaneously. 3 mg/kg SAA was orally administered for six weeks and 150 mg/kg Metformin was selected as a positive group. At the end of this period, cardiac function was assessed by ultrasound, electrocardiogram, and relevant cardiac injury biomarkers testing. Treatment with SAA improved cardiac function, glucose, and lipid levels, mitochondrial respiration, and suppressed myocardial inflammation and apoptosis. Furthermore, SAA treatment inhibits the apoptosis pathway through CRYAB in diabetic cardiomyopathy rats. As a result, this study not only provides new insights into the mechanism of SAA against DCM but also provides new therapeutic ideas for the discovery of anti-DCM compounds in the clinic.

ABSTRACT: Poultry is susceptible to fatty liver which lead to decrease egg production and increase mortality. But the potential molecular mechanisms remain largely unclear. In the current study, in combination with transcriptome sequencing and miRNA sequencing data analysis from F1 generation of the normal liver and fatty liver tissues, the differentially expressed miR-375 and its target gene RBPJ were screened and verified. The expression levels of miR-375 and RBPJ gene in the liver between control and fatty liver groups of F0-F3 generation for Jingxing-Huang (JXH) chicken are different significantly (P < 0.05 or P < 0.01). And downregulated RBPJ expression can promote TG content and lipid droplets in primary hepatocytes cultured in vitro (P < 0.01). Cell proliferation-related genes, including PMP22, IGF-1, IGF-2, and IGFBP-5, increased or decreased significantly after overexpression or knock-down RBPJ (P < 0.05 or P < 0.01), respectively. This study uniquely revealed that miR-375 induced lipid synthesis and inhibited cell proliferation may partly due to regulation of RBPJ expression, thereby involving in fatty liver formation and inheritance in chicken. The results could be useful in identifying candidate genes and revealing the pathogenesis of fatty liver that may be used for disease-resistance selective breeding in chicken.

Objectives: Norovirus is associated with one-fifth of all gastroenteritis cases, but basic epidemiological data is lacking, especially in developing countries. As long-term surveillance on norovirus gastroenteritis is scarce in western China, this study aims to update the epidemiological knowledge of norovirus gastroenteritis and to characterize the genotypes of norovirus strains. Methods: Stool samples were collected from hospitalized children under 5 years old with gastroenteritis in Chengdu, China. All samples were tested for norovirus as well as rotavirus, sapovirus, enteric adenovirus, and astrovirus by real-time RT-PCR. RdRp and VP1 genes were sequenced in norovirus-positive samples to investigate viral phylogenies. Results: Of the 1181 samples collected from 2015 to 2019, 242 (20.5%) were positive for norovirus.Among norovirus-positive cases, 65 cases had co-infection with another virus; norovirus/enteric adenovirus was most frequently detected (50.8%, 33/65). The highest positive rate was observed in children aged 13–18 months (23.7%, 68/287). Norovirus infection peaked in autumn (36.6%, 91/249), followed by summer (20.3%, 70/345). Pearson correlation analysis showed significant correlation between the norovirus-positive rate and humidity (r = 0.773, P

Pulmonary arterial hypertension (PAH) is a severe cardiopulmonary dysfunctional disease, characterized by progressive vascular remodeling. Inflammation is an increasingly recognized feature of PAH, which is important for the initiation and maintenance of vascular remodeling. High levels of various inflammatory mediators have been documented in both PAH patients and experimental models of PAH. Similarly, multiple immune cells were found to accumulate in and around the wall of remodeled pulmonary vessels and in the vicinity of plexiform lesions, respectively. On the other hand, inflammation is also a bridge from autoimmune diseases to PAH. Autoimmune diseases always lead to chronic inflammation, characterized by the low-level persistent infiltration of immune cells, and elevated levels of several pro-inflammatory cytokines and chemokines. In addition, circulating autoantibodies are found in the peripheral blood of patients, indicating a possible role of autoimmunity in the pathogenesis of PAH. Thus, anti-inflammatory and immunotherapy might be new strategies to prevent or even reverse the process of PAH. Many anti-inflammatory agents and immunotherapies have been confirmed in animal models while some clinical trials employing immunotherapies are completed or currently underway. Here, we review pathological mechanisms associated with inflammation and immunity in the development of PAH, and discuss potential interventions for the treatment of PAH.

Background: The role of peripheral blood lymphocyte (pBL) in breast cancer has long been studied. However, the predictive role of pBL in advanced breast cancer (ABC) is poorly understood. Methods: A total of 303 patients with ABC were consecutively recruited at our center between January 2015 and September 2019. At baseline, pBL subtypes were detected in all patients with 229 blood samples available for circulating tumor DNA (ctDNA) detection. pBL was analyzed through flow cytometry. ctDNA-based gene mutations were detected using next generation sequencing. The cutoff value of pCTL was estimated by X-tile software. Progression free survival (PFS) was estimated by Kaplan-Meier curve and Cox hazard proportion regression model, with difference detection by log-rank test. Results: Median follow-up time of the study was 21.0 months. The median age of diagnosis was 52.0 years. Among the pBL subtypes, only pCTL level was found predictive for PFS in the HER2+ patients whom received anti-HER2 therapy (13.1 vs. 5.6 months, P = 0.001). However, the predictive role of pCTL was not found in HR-positive (P = 0.716) and TNBC (P = 0.202). pCTL high associated with suppressive immune indictors including lower CD4/CD8 ratio (P = 0.004) and high level of Treg cell (P = 0.004). High occurrence of FGFR1 amplification which has been reported as immune suppressor was also found in HER2+ patients with pCTL high (22.2% vs. 4.3%, P = 0.048). Conclusions: Higher pCTLs level associated with shorter PFS and FGFR1 mutation in HER2+ ABC patients.

Therapies against hepatitis B virus (HBV) have improved in recent decades; however, the development of individualized treatments has been limited by the lack of individualized infection models. In this study, we used human induced pluripotent stem cell (hiPSC) to generate a functional liver organoid (LO) that inherited the genetic background of the donor, and evaluated its application in modeling HBV infection and exploring virus–host interactions. To establish a functional hiPSC-LO, we cultured hiPSC-derived endodermal, mesenchymal, and endothelial cells with a chemically defined medium in a three-dimensional microwell culture system. Based on cell-cell interactions, these cells could organize themselves and gradually differentiate into a functional organoid, which exhibited stronger hepatic functions than hiPSC derived hepatic like cell (HLC). Moreover, the functional LO demonstrated more susceptibility to HBV infection than hiPSC-HLC, and could maintain HBV propagation and produce infectious virus for a prolonged duration. Furthermore, we found that virus infection could cause hepatic dysfunction of hiPSC-LOs, with down-regulation of hepatic gene expression, induced release of early acute liver failure markers, and altered hepatic ultrastructure. Therefore, our study demonstrated that HBV infection in hiPSC-LOs could recapitulate virus life cycle and virus induced hepatic dysfunction, suggesting that hiPSC-LOs may provide a promising individualized infection model for the development of individualized treatment for hepatitis. Keywords: Liver organoid, hiPSC, Hepatitis B virus, Virus-host interactions

Summary: Radio frequency identification (RFID) is a cost-effective and durable method to trace and track individual objects in multiple contexts by wirelessly providing digital signals; RFID is thus widely used in many fields. Here, we implement this concept to biological tissues by producing a compact RFID chip-incorporated organoid (RiO). The 0.4 mm RFID chips are reproducibly integrated inside the self-assembling organoids from 10 different induced pluripotent stem cell (iPSC) lines from healthy and diseased donors. We use the digitalized RiO to conduct a phenotypic screen on a pool of RiO, followed by detection of each specific donor in situ. Our proof-of-principle experiments demonstrated that a severely steatotic phenotype could be identified by RFID chip reading and was specific to a genetic disorder of steatohepatitis. Given evolving advancements surrounding RFID technology, the digitalization principle outlined here will expand organoid medicine potential toward drug development, precision medicine, and transplant applications. : Cell Biology; Stem Cells Research; Bioengineering Subject Areas: Cell Biology, Stem Cells Research, Bioengineering

Summary: Early endoderm progenitors naturally possess robust propagating potential to develop a majority of meter-long gastrointestinal tracts and are therefore considered as a promising source for therapy. Here, we demonstrated the reproducible generation of human CDX2+ posterior gut endoderm cells (PGECs) from five induced pluripotent stem cell clones by manipulating FGF, TGF, and WNT signaling. Transcriptome analysis suggested that putative PGECs harbored an intermediate signature profile between definitive endoderm and organ-specific endoderm. We found that combinatorial EGF, VEGF, FGF2, Chir99021, and A83-01 treatments selectively amplify storable PGECs up to 1021 cell scale without any gene transduction or feeder use. PGECs, compared with induced pluripotent stem cells, showed stable differentiation propensity into multiple endodermal lineages without teratoma formation. Furthermore, transplantation of PGEC-derived liver bud organoids showed therapeutic potential against fulminant liver failure. Together, the robustly amplified PGECs may be a promising cellular source for endoderm-derived organoids in studying human development, modeling disease, and, ultimately, therapy. : In this article, Takebe, Taniguchi, and colleagues derived a unique population of CDX2+ posterior endoderm progenitors (PGECs) from human pluripotent stem cells that are highly expandable and storable in a chemically defined condition. CDX2+ endoderm progenitors can form multiple endodermal organoids. Transplantation of human liver bud organoids from robustly propagated PGECs rescued lethal liver failure of immunodeficient mice. Keywords: progenitors, posterior gut endoderm cells, organoid, liver bud, transplant, human, pluripotent stem cells, iPSC, CDX2, intestine

Summary: Background: Spectral-domain optical coherence tomography (SDOCT) can be used to detect glaucomatous optic neuropathy, but human expertise in interpretation of SDOCT is limited. We aimed to develop and validate a three-dimensional (3D) deep-learning system using SDOCT volumes to detect glaucomatous optic neuropathy. Methods: We retrospectively collected a dataset including 4877 SDOCT volumes of optic disc cube for training (60%), testing (20%), and primary validation (20%) from electronic medical and research records at the Chinese University of Hong Kong Eye Centre (Hong Kong, China) and the Hong Kong Eye Hospital (Hong Kong, China). Residual network was used to build the 3D deep-learning system. Three independent datasets (two from Hong Kong and one from Stanford, CA, USA), including 546, 267, and 1231 SDOCT volumes, respectively, were used for external validation of the deep-learning system. Volumes were labelled as having or not having glaucomatous optic neuropathy according to the criteria of retinal nerve fibre layer thinning on reliable SDOCT images with position-correlated visual field defect. Heatmaps were generated for qualitative assessments. Findings: 6921 SDOCT volumes from 1 384 200 two-dimensional cross-sectional scans were studied. The 3D deep-learning system had an area under the receiver operation characteristics curve (AUROC) of 0·969 (95% CI 0·960–0·976), sensitivity of 89% (95% CI 83–93), specificity of 96% (92–99), and accuracy of 91% (89–93) in the primary validation, outperforming a two-dimensional deep-learning system that was trained on en face fundus images (AUROC 0·921 [0·905–0·937]; p

The safety of feeding transgenic cry1Ab/cry1Ac rice (a genetically modified (GM) rice variety) to broilers was examined from an immunological perspective. Hatchling Arbor Acres chickens (240) were assigned to two dietary treatments (diets containing GM or non-GM rice) with 12 replicates per group and 10 birds per replicate. Traits were measured on one randomly selected bird from each replicate at d 21 and 42. The 42-d feeding trial revealed that cry1Ab/cry1Ac rice had no significant effect relative to non-GM rice on body weight and the immune organ indices. No significant pathological lesion in the spleen and bursa of Fabricius was found in the GM rice group. There were no significant differences in serum concentrations of immunoglobulin Y (IgY), IgM, interleukin 4 (IL-4) and IL-6 between the two groups at d 21 or 42, except for IL-6 being higher (P

Purpose: To evaluate the effectiveness of oxygen nebulization at preventing radiotherapy-induced mucositis in patients with nasopharyngeal cancer. Methods: Sixty patients with nasopharyngeal cancer treated with simultaneous integrated boost intensity-modulated radiotherapy were randomly assigned to oxygen nebulization or ultrasonic nebulization groups; treatment was once daily for 20 minutes. All patients received routine oral care. We compared saliva pH and volume, food intake, and change in oral mucosa during radiotherapy, and dry mouth and sore throat after radiotherapy between the two groups. Results: There were significant differences in the incidence of grade III or IV mucositis, saliva volume and pH, and dry mouth and sore throat between the two groups when the total dose was 33 Gy (p

Gamma delta T cells play a crucial role in anti-tumor immunity due to their cytotoxic properties. However, the role and extent of γδ T cells in production of pro-tumorigenic interleukin-17 (IL-17) within the tumor microenvironment of colorectal cancer (CRC) remains controversial. In this study, we re-analyzed nine published human CRC whole-tissue single-cell RNA sequencing datasets, identifying 18,483 γδ T cells out of 951,785 total cells, in the neoplastic or adjacent normal tissue of 165 human CRC patients. Our results confirm that tumor-infiltrating γδ T cells exhibit high cytotoxicity-related transcription in both tumor and adjacent normal tissues, but critically, none of the γδ T cell clusters showed IL-17 production potential. We also identified various γδ T cell subsets, including poised effector-like T cells, tissue-resident memory T cells, progenitor exhausted-like T cells, and exhausted T cells, and noted an increased expression of cytotoxic molecules in tumor-infiltrating γδ T cells compared to their normal area counterparts. We proposed anti-tumor γδ T effector cells may arise from tissue-resident progenitor cells based on the trajectory analysis. Our work demonstrates that γδ T cells in CRC primarily function as cytotoxic effector cells rather than IL-17 producers, mitigating the concerns about their potential pro-tumorigenic roles in CRC, highlighting the importance of accurately characterizing these cells for cancer immunotherapy research and the unneglectable cross-species discrepancy between the mouse and human immune system in the study of cancer immunology., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024. Published by Elsevier Inc.)

Background: Chronic postoperative surgical pain (CPSP) is a frequent complication following breast surgery and poses a challenge in terms of treatment. We hypothesized that the incidence of CPSP would be reduced at 3 months post-breast surgery with the administration of S-ketamine compared to a placebo., Patients and Methods: Participants were recruited and randomly assigned to either the S-ketamine group (S) or the control group (C). In group S, S-ketamine was administered as a 1.5 mg kg -1 bolus followed by 2 mg kg -1 h -1 infusion, while in group C, a placebo of 0.9% saline was administered in the same volume and rate as S-ketamine. The primary outcome was the incidence of CPSP, measured using a 0-10 numeric rating scale (NRS), at 3 months postsurgery., Results: A total of 72 patients scheduled for mastectomy were enrolled (group S, n = 33; group C, n = 32). The incidence of CPSP at 3 months postsurgery was significantly lower in group S compared to group C (18.2% vs. 48.3%, P < .05). There was no statistical difference between the 2 groups in terms of the incidence of moderate to severe pain. NRS scores for postoperative pain at rest and during movement were significantly lower at 4 h and 24 h post-surgery (P < .05, respectively). Patients in Group S had lower Patient Health Questionnaire-9 (PHQ-9) scores at one week and 3 months post-surgery compared to Group C (P < .05, respectively)., Conclusion: S-ketamine infusion reduces the incidence of CPSP 3 months after breast surgery., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Protein-based subunit vaccines are weakly immunogenic, and developing self-adjuvanting vaccines with adjuvant conjugated to antigen is a promising approach for generating optimal immune responses. Here, we report a novel adjuvant-protein conjugate vaccine based on versatile oxime ligation technique. Firstly, the adjuvant properties of a series of TLR7 and TLR7/8 small molecule agonists in self-adjuvanting vaccines were systematically compared by coupling them to proteins in consistent ratio via p-carboxybenzaldehyde (p-CBA) for the first time. All conjugate vaccines induced cytokine secretion in murine and human macrophages in vitro, and promoted specific antibody production in vivo. Notably, a conjugate containing imidazoquinoline TLR7/8 agonist (TLR7/8a1) showed the greatest enhancement in Th1/2 balanced antibody response. To minimize the interference with the protein antigenic integrity, we further developed a systematic glycoconjugation strategy to conjugate this TLR7/8a1 onto the glycan chains of SARS-CoV-2 S1 glycoprotein via oxime ligation, in which S1 containing different numbers of aldehyde groups were obtained by differential periodate oxidation. The resulting TLR7/8a1-S1 conjugate triggered a potent humoral and cellular immunity in vivo. Together these data demonstrate the promise of these TLR7 and TLR7/8 agonists as effective built-in adjuvants, and the versatile oxime ligation strategy might broaden potential applications in designing different conjugate vaccines., 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 this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Bioenvironmental and biological factors have the potential to contribute to the development of glioma, a type of brain tumor. Recent studies have suggested that a unique circular RNA called circCSNK1G3 could play a role in promoting the growth of glioma cells. It does this by stabilizing a specific microRNA called miR-181 and reducing the expression of a tumor-suppressor gene known as chromobox protein homolog 7 (CBX7). To further investigate circCSNK1G3 and its effects on glioma, we utilized a nanoplatform called adeno-associated virus (AAV)-RNAi.To explore the functional implications of circCSNK1G3, we employed siRNA to silence its expression. Along with these effects, the silencing of circCSNK1G3 led to a depletion of miR-181d and an upregulation of CBX7. When we introduced miR-181d mimics, which artificially increase the levels of miR-181d, the anti-glioma cell activity induced by circCSNK1G3 siRNA was almost completely reversed. Conversely, inhibiting miR-181d mimicked the effects of circCSNK1G3 silencing. Moreover, when we overexpressed circCSNK1G3 in glioma cells, we observed an elevation of miR-181d and a depletion of CBX7. We found that the growth of A172 xenografts (tumors) carrying circCSNK1G3 shRNA was significantly inhibited. In these xenograft tissues, we detected a depletion of circCSNK1G3 and miR-181d, as well as an upregulation of CBX7., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Semi-supervised medical image segmentation presents a compelling approach to streamline large-scale image analysis, alleviating annotation burdens while maintaining comparable performance. Despite recent strides in cross-supervised training paradigms, challenges persist in addressing sub-network disagreement and training efficiency and reliability. In response, our paper introduces a novel cross-supervised learning framework, Quality-driven Deep Cross-supervised Learning Network (QDC-Net). QDC-Net incorporates both an evidential sub-network and an vanilla sub-network, leveraging their complementary strengths to effectively handle disagreement. To enable the reliability and efficiency of semi-supervised training, we introduce a real-time quality estimation of the model's segmentation performance and propose a directional cross-training approach through the design of directional weights. We further design a truncated form of sample-wise loss weighting to mitigate the impact of inaccurate predictions and collapsed samples in semi-supervised training. Extensive experiments on LA and Pancreas-CT datasets demonstrate that QDC-Net surpasses other state-of-the-art methods in semi-supervised medical image segmentation. Code release is available at https://github.com/Medsemiseg., Competing Interests: Declaration of competing interest We declare that we have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Wenchang chicken, a prized local breed in Hainan Province of China renowned for its exceptional adaptability to tropical environments and good meat quality, is deeply favored by the public. However, an insufficient understanding of its population architecture and the unclear genetic basis that governs its typical attributes have posed challenges in the protection and breeding of this precious breed. To address these gaps, we conducted whole-genome resequencing on 200 Wenchang chicken samples derived from 10 distinct strains, and we gathered data on an array of 21 phenotype traits. Population genomics analysis unveiled distinctive population structures in Wenchang chickens, primarily attributed to strong artificial selection for different feather colors. Selection sweep analysis identified a group of candidate genes, including PCDH9, DPF3, CDIN1, and SUGCT, closely linked to adaptations that enhance resilience in tropical island habitats. Genome-wide association studies (GWAS) highlighted potential candidate genes associated with diverse feather color traits, encompassing TYR, RAB38, TRPM1, GABARAPL2, CDH1, ZMIZ1, LYST, MC1R, and SASH1. Through the comprehensive analysis of high-quality genomic and phenotypic data across diverse Wenchang chicken resource groups, this study unveils the intricate genetic backgrounds and population structures of Wenchang chickens. Additionally, it identifies multiple candidate genes linked to environmental adaptation, feather color variations, and production traits. These insights not only provide genetic reference for the purification and breeding of Wenchang chickens but also broaden our understanding of the genetic basis of phenotypic diversity in chickens., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

To improve the hydration properties of high-temperature pressed peanut protein isolate (HPPI), we investigated the effect of cold plasma (CP) oxidation on functional and structural properties. Compared to HPPI, the hydrated molecules number and the surface contact angle were significantly decreased at 70 W, from 77.2 × 10 9 to 17.7 × 10 9 and from 85.74° to 57.81°, respectively. The reduction of the sulfhydryl content and the increase of the disulfide bond and di-tyrosine content indicated that the structural transformation was affected by the oxidation effect. In terms of structural changes, a stretched tertiary structure, ordered secondary structure, and rough apparent structure were observed after CP treatment. Additionally, the enhancement of surface free energy and group content such as -COOH, -CO and -OH on the surface of HPPI contributed to the formation of hydrated crystal structures. In general, the oxidation effect of CP effectively improved the hydration properties of HPPI and broaden its application field., 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 this paper., (Copyright © 2023. Published by Elsevier B.V.)

Remdesivir (RDV) and tenofovir alafenamide (TAF) are prodrugs designed to be converted to their respective active metabolites. Plasma protein binding (PPB) determination of these prodrugs is important for patients with possible alteration of free fraction of the drugs due to plasma protein changes in renal impairment, hepatic impairment, or pregnancy. However, the prodrugs' instability in human plasma presents a challenge for accurate PPB determination. In this research work, two approaches were used in the method development and qualification for PPB assessment of RDV and TAF. For RDV, dichlorvos was used to inhibit esterase activity to stabilize the prodrug in plasma during equilibrium dialysis (ED). The impact of dichlorvos on protein binding was evaluated and determined to be insignificant by comparing the unbound fraction (f u ) determined by the ED method with dichlorvos present and the f u determined by an ultrafiltration method without dichlorvos. In contrast to RDV, TAF degradation in plasma is ∼3-fold slower, and TAF stability cannot be improved by dichlorvos. Fit-for-purpose acceptance criteria for the TAF PPB method were chosen, and an ED method was developed based on these criteria. These two methods were then qualified and applied for PPB determinations in clinical studies., 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 this paper., (Copyright © 2023 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)

Background: To meet the growing global demand for rehabilitation services, the World Health Organization (WHO) launched Rehabilitation 2030. This study was commissioned by the WHO to investigate the integration degree of traditional Chinese medicine (TCM) in Chinese health system rehabilitation services and the demand for TCM rehabilitation in China., Methods: Twenty TCM rehabilitation experts and relevant government administrators were invited to complete the questionnaire between September 2019 and January 2022. The development of traditional, complementary, and integrative medicine (TCI) rehabilitation in China was assessed primarily based on six different health system components., Results: 26 policies, regulations, and national strategic plans related to TCI rehabilitation were issued by relevant government departments since 2002; notably, 14 policies related to TCI rehabilitation development were intensively introduced from 2016 to 2021. These policies cover the three main areas of financing, infrastructure development, and service delivery. The National Administration of Traditional Chinese Medicine's investment in TCM clinical capacity infrastructure and scientific research in 2019-2021 increased by 66% compared to 2010-2012, and the average number of TCM hospitals with rehabilitation departments in 2020 increased by 6.5% compared to 2018. The proportion of community health service centers providing TCM services in primary medical and health institutions has increased by 30.8% over the past 10 years., Conclusion: Long-term continuous policies, substantial financial investment, and expansion of the scope of TCI rehabilitation services in primary care institutions have effectively contributed to the rapid development of TCI rehabilitation. However, human resources and financing mechanisms for TCI rehabilitation need further improvement., Competing Interests: The authors declare that they have no conflicts of interest., (© 2023 Korea Institute of Oriental Medicine. Published by Elsevier B.V.)

Poultry is susceptible to fatty liver which lead to decrease egg production and increase mortality. But the potential molecular mechanisms remain largely unclear. In the current study, in combination with transcriptome sequencing and miRNA sequencing data analysis from F1 generation of the normal liver and fatty liver tissues, the differentially expressed miR-375 and its target gene RBPJ were screened and verified. The expression levels of miR-375 and RBPJ gene in the liver between control and fatty liver groups of F0-F3 generation for Jingxing-Huang (JXH) chicken are different significantly (P < 0.05 or P < 0.01). And downregulated RBPJ expression can promote TG content and lipid droplets in primary hepatocytes cultured in vitro (P < 0.01). Cell proliferation-related genes, including PMP22, IGF-1, IGF-2, and IGFBP-5, increased or decreased significantly after overexpression or knock-down RBPJ (P < 0.05 or P < 0.01), respectively. This study uniquely revealed that miR-375 induced lipid synthesis and inhibited cell proliferation may partly due to regulation of RBPJ expression, thereby involving in fatty liver formation and inheritance in chicken. The results could be useful in identifying candidate genes and revealing the pathogenesis of fatty liver that may be used for disease-resistance selective breeding in chicken., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Three undescribed meroterpenoids, named bipolacochlioquinones A-C, together with seven known compounds, were isolated from the plant endophytic fungus Bipolaris victoriae S27 derived from the fresh stems of Rubia podantha Diels. Their structures were mainly determined by extensive spectroscopic analysis. The relative configurations of bipolacochlioquinones A-C were assigned using the ROESY spectrum, comparison of their spectral data with that reported in the literatures, and NMR calculations. Moreover, their complete absolute configurations were further established by electronic circular dichroism calculations using density functional theory. Among them, bipolacochlioquinone A is found to represent the first example of previously undescribed 6/6/6/6/6 pentacyclic dioxane-containing cochlioquinones, and bipolacochlioquinone B possesses a rare 6/6/6/6/5 pentacyclic system bearing a tetrahydrofuran ring fused to a polyketide and a sesquiterpenoid subunit. All compounds were evaluated for their inhibitory effects on tumor growth, metastasis, and the NF-κB signaling pathway. Among them, bipolacochlioquinone C and cochlioquinone A show the most potent cytotoxicities and NF-κB inhibitory activities. The effects of bipolacochlioquinone C and cochlioquinone A on the expression of NF-κB-associated proteins were also evaluated using western blotting. These results indicate that bipolacochlioquinone C and cochlioquinone A can inhibit the growth and metastasis of HCT116 and MDA-MB-231 cells by suppressing the NF-κB signaling pathway., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Pulmonary arterial hypertension (PAH) is a severe cardiopulmonary dysfunctional disease, characterized by progressive vascular remodeling. Inflammation is an increasingly recognized feature of PAH, which is important for the initiation and maintenance of vascular remodeling. High levels of various inflammatory mediators have been documented in both PAH patients and experimental models of PAH. Similarly, multiple immune cells were found to accumulate in and around the wall of remodeled pulmonary vessels and in the vicinity of plexiform lesions, respectively. On the other hand, inflammation is also a bridge from autoimmune diseases to PAH. Autoimmune diseases always lead to chronic inflammation, characterized by the low-level persistent infiltration of immune cells, and elevated levels of several pro-inflammatory cytokines and chemokines. In addition, circulating autoantibodies are found in the peripheral blood of patients, indicating a possible role of autoimmunity in the pathogenesis of PAH. Thus, anti-inflammatory and immunotherapy might be new strategies to prevent or even reverse the process of PAH. Many anti-inflammatory agents and immunotherapies have been confirmed in animal models while some clinical trials employing immunotherapies are completed or currently underway. Here, we review pathological mechanisms associated with inflammation and immunity in the development of PAH, and discuss potential interventions for the treatment of PAH., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Nine new pyrrole alkaloids, including two undescribed dimeric pyrrole 2‑carbaldehyde alkaloids, lepipyrrolins A-B (1-2), seven pyrrole-alkaloid derivatives, macapyrrolins D-J (3-9), along with three known ones (10-12) were isolated from the rhizomes of Lepidium meyenii. Their structures and absolute configurations were demonstrated by extensive spectroscopic data (1D, 2D NMR, HRESIMS), and calculated electronic circular dichroism (ECD) experiment. Compounds 1, 3-12 were tested for their nitric oxide inhibitory effects. Furthermore, compound 1 was evaluated for its cytotoxic activity against five human tumor cell lines (HL-60, SMMC-7221, A549, MCF-7, and SW480) in vitro, and displayed selective cytotoxicity against SMMC-7721 with IC 50 value of 16.78 ± 0.49 μM., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: To evaluate the efficacy and safety of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) for the treatment of cervical squamous intraepithelial lesion (SIL)., Methods: We prospectively screened and enrolled patients with cervical SIL and persistent high-risk human papilloma virus (HR-HPV) infection to receive ALA-PDT from March 27, 2019, to January 23, 2020, at Beijing Youan Hospital, China. The primary outcome was the remission rate of SIL and HPV. The secondary outcome was the symptom improvement and adverse events of ALA-PDT in these cases., Results: 54 patients with cervical SIL and persistent HR-HPV infection were enrolled and divided these individuals into three groups: high-grade squamous intraepithelial lesion (HSIL) group (10 patients), low-grade squamous intraepithelial lesion (LSIL) group (33 patients), and simple HR-HPV infection group (11 patients). 49 of 54 patients finished six sessions treatment and 46 of 49 patients complete the follow-up. After six sessions' treatment, HR-HPV remission rates were 71.43 %(5/7)in the simple HR-HPV infection group, 63.64 %(14/22) in the LSIL group, and 50 %(4/8) in the HSIL group. The histology remission rates were 80 %(4/5) in the simple HR-HPV infection group, 69.57 %(16/23)in the LSIL group, and 75 % (6/8) in the HSIL group. Symptoms improvement rates in the simple HR-HPV infection, LSIL group, and HSIL group were 100 %(5/5), 66.67 %(5/15) and 71.43 %(5/7). No severe adverse events or systemic side effects were observed in treatment., Conclusion: Topical ALA-PDT is an effective and safe treatment for cervical SIL., (Copyright © 2021. Published by Elsevier B.V.)

Background: The role of peripheral blood lymphocyte (pBL) in breast cancer has long been studied. However, the predictive role of pBL in advanced breast cancer (ABC) is poorly understood., Methods: A total of 303 patients with ABC were consecutively recruited at our center between January 2015 and September 2019. At baseline, pBL subtypes were detected in all patients with 229 blood samples available for circulating tumor DNA (ctDNA) detection. pBL was analyzed through flow cytometry. ctDNA-based gene mutations were detected using next generation sequencing. The cutoff value of pCTL was estimated by X-tile software. Progression free survival (PFS) was estimated by Kaplan-Meier curve and Cox hazard proportion regression model, with difference detection by log-rank test., Results: Median follow-up time of the study was 21.0 months. The median age of diagnosis was 52.0 years. Among the pBL subtypes, only pCTL level was found predictive for PFS in the HER2+ patients whom received anti-HER2 therapy (13.1 vs. 5.6 months, P = 0.001). However, the predictive role of pCTL was not found in HR-positive (P = 0.716) and TNBC (P = 0.202). pCTL high associated with suppressive immune indictors including lower CD4/CD8 ratio (P = 0.004) and high level of Treg cell (P = 0.004). High occurrence of FGFR1 amplification which has been reported as immune suppressor was also found in HER2+ patients with pCTL high (22.2% vs. 4.3%, P = 0.048)., Conclusions: Higher pCTLs level associated with shorter PFS and FGFR1 mutation in HER2+ ABC patients., Competing Interests: Declaration of competing interest The authors declare no potential conflicts of interest., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Breast cancer is the most common cause of cancer-related death in women worldwide. MicroRNA (miRNA) ectopic expression has been reported to be involved in the regulation of gene expression in breast cancer. We screened several differentially expressed miRNAs associated with breast cancer chemoresistance, growth, and metastasis using a miRNA microarray. Increased expression of miR-4472 has been associated with larger breast tumors and chemoresistance. However, the biologic function of miR-4472 and its molecular mechanisms in cancer progression have not yet been reported., Materials and Methods: Real-time quantitative polymerase chain reaction was used to measure the expression of miR-4472 in breast cancer tissue and cell lines. The biologic functions of miR-4472 and its target gene were explored using Transwell, cell proliferation, and flow cytometry assays. Bioinformatics tools, dual-luciferase reporter assays, and Western blot were used to identify the target genes of miR-4472. Western blot was used to explain the participation of miR-4472 and target gene in epithelial-to-mesenchymal transition., Results: miR-4472 was significantly upregulated in highly metastatic breast cancer tissues, and its expression was positively associated with larger tumor size and advanced pTNM stage. miR-4472 promoted breast cancer cell metastasis and growth. Repulsive guidance molecule A (RGMA) was a direct target gene of miR-4472. RGMA was identified as a suppressor in cancer metastasis. miR-4472 downregulated expression of RGMA and promoted epithelial-to-mesenchymal transition by suppressing E-cadherin and initiating vimentin, β-catenin, and Slug., Conclusions: miR-4472 contributes to the progression of breast cancer by regulating RGMA expression and inducing epithelial-to-mesenchymal transition, indicating that miR-4472/RGMA might serve as a therapeutic target for breast cancer., (Copyright © 2019 Elsevier Inc. All rights reserved.)

In recent years, the development of Chinese herbal medicine (CHM) has been challenged by shortages of CHM resources and drug safety concerns related to end products. There have been significant efforts by Chinese scholars to tackle these challenges, which are revealed by analyzing the research trend of CHM resources via surveying Chinese Traditional and Herbal Drugs (Zhong Cao Yao), a representative journal in CHM. Our study focused on 781 articles in CHM resources from 2013 to 2018 and included four subject areas: germplasm resources, quality analysis and evaluation, cultivation, and bioengineering of CHM. Discussion and prospective for future investigations were also presented, including: construct the core germplasm of medicinal plants and expand germplasms; combine molecular research with field experiments and promote the deeper study of cultivation of CHM plants; improve the quality evaluation method of CHM and strengthen the identification of Chinese patented medicines; promote the sustainable development of CHM resources by utilizing bioengineering and synthetic biology. This study helps international scholars understand the status quo of CHM research and provides theoretical support for the healthy, modern, and international development of CHM, and it will facilitate the sustainable development of the traditional Chinese medicine industry., Competing Interests: The authors declare no conflict of interests., (© 2019 Tianjin Press of Chinese Herbal Medicines. Published by Elsevier B.V.)

Contamination of vegetable plants with cadmium (Cd) has become a serious issue in recent years. In the present study, pakchoi (Brassica chinensis L.) grown in Cd-contaminated soil inoculated with abscisic acid (ABA)-generating bacteria, Azospirillum brasilense and Bacillus subtilis, showed 28%-281% and 26%-255% greater biomass, and 40%-79% and 43%-77% lower Cd concentrations, respectively, than those of the control bacteria-free plants. These treatments also alleviated the Cd-induced photosynthesis inhibition and oxidative damage (indicated by malondialdehyde [MDA], H 2 O 2 , and O 2 • - ). Furthermore, the application of bacteria also remarkably improved the levels of antioxidant-related compounds (total phenolics, total flavonoids, ascorbate, and 2,2-diphenyl-1-picrylhydrazyl [DPPH] activity) and nutritional quality (soluble sugar and soluble protein) in the Cd-supplied plants. Based on these results, we conclude that the application of ABA-generating bacteria might be an alternative strategy for improving the biomass production and quality of vegetable plants grown in Cd-contaminated soil., (Copyright © 2019. Published by Elsevier Inc.)

Background: microRNA-139 (miR-139) is dysregulated in various types of tumors and plays a key role in carcinogenesis. miR-139 may be used as a diagnostic and prognostic biomarker of cancers. However, the data from the literature are not consistent. The present study aimed to verify the prognostic and diagnostic values of miR-139 in solid tumors., Data Sources: PubMed, Web of Science and Embase databases were searched and publications from January 2011 to August 2017 were included. We used Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) database to further validate this meta-analysis., Results: Eight individual studies from seven articles were included. Pooled analyses showed that low miR-139 expression was related to worse overall survival (OS) [hazard ratio (HR) = 2.27; 95% confidence intervals (CI): 1.74-2.95; P < 0.001] in solid tumors, including hepatocellular carcinoma (HCC) and glioblastoma multiforme (GBM), consisting with the results of TCGA. However, our results of CRC showed that low miR-139 expression was associated with poor OS which was contradictory with the results in TCGA database and need larger samples to validate the phenomenon; whereas for CRC patients, high miR-139 expression predicted poor RFS, which was in good accordance with TCGA results. The results of 27 microarrays from GEO database showed that miR-139 expression levels were lower in tumor tissues compared to adjacent non-tumor tissues or healthy tissues. Decreased miR-139 expression was also significantly correlated with poor differentiation grade (OR = 3.57; 95% CI: 1.44-8.85; P = 0.006). However, the combined data indicated that no associations between miR-139 expression and the following parameters such as age (pooled OR = 1.50; 95% CI: 0.69-3.24; P = 0.304), gender (pooled OR = 0.92; 95% CI: 0.56-1.51; P = 0.738), tumor size (pooled OR = 1.51; 95% CI: 0.69-3.31; P = 0.298), late tumor-node-metastasis stage (pooled OR = 1.63; 95% CI: 0.99-2.68; P = 0.057) and lymph-node-metastasis (pooled OR = 0.66; 95% CI: 0.34-1.28; P = 0.222)., Conclusions: Low miR-139 expression was related to poor prognosis in HCC and GBM, which could be regarded as a potential prognostic biomarker. However, its precise functional role in CRC still need to be further investigated through larger samples and multicenter studies., (Copyright © 2018 First Affiliated Hospital, Zhejiang University School of Medicine in China. Published by Elsevier B.V. All rights reserved.)

Peroxiredoxin 3 (PRX3) is predominantly located in mitochondria and plays a major role in scavenging hydrogen peroxide of mitochondria. In the present study, we detected plasma PRX3 in pregnant women receiving oral glucose tolerance test at 24-28 gestational weeks. Plasma PRX3 was significantly increased about 1 h later than insulin secretion. In vitro detection of PRX3 in mouse islet cells showed up-regulation by more than 2-fold at 1 h and reached its top at 2 h of glucose stimulation, and the PRX3 level in cultured mediums was concomitantly elevated in a glucose concentration-dependent manner. In addition, both fasting plasma insulin and PRX3 were significantly higher in the subjects of term pregnancy as compared to that at 24-28 gestational weeks, and there was a positive correlation between plasma PRX3 and insulin. Our results indicate that PRX3 plays an active role in the response to insulin release. The positive association of plasma PRX3 and insulin suggest PRX3 to be a potential indicator of high insulin resistance., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Renal interstitial fibrosis is an inevitable consequence of virtually every type of chronic kidney disease. The underlying mechanisms, however, are not completely understood. In the present study, we identified surfactant protein A (SP-A) as a novel protein factor involved in the renal fibrosis induced by unilateral ureter obstruction (UUO). UUO induced SP-A expression in mouse kidney epithelium, likely due to the increased acidic stress and inflammation. Interestingly, SP-A deficiency aggravated UUO-prompted kidney structural damage, macrophage accumulation, and tubulointerstitial fibrosis. SP-A deficiency appeared to worsen the fibrosis by enhancing interstitial myofibroblast accumulation. Moreover, SP-A deficiency increased the expression of TGF-β1, the major regulator of kidney fibrosis, particularly in the interstitial cells. Mechanistically, SP-A deficiency increased the expression and release of high mobility group box 1 (HMGB1), a factor regulating TGF-β expression/signaling and implicated in renal fibrosis. SP-A also blocked HMGB1 activities in inducing TGF-β1 expression and myofibroblast transdifferentiation from kidney fibroblasts, demonstrating that SP-A protected kidney by impeding both the expression and fibrogenic function of HMGB1. Since SP-A physically interacted with HMGB1 both in vitro and in kidney tissue in vivo, SP-A may exert its protective role by binding to HMGB1 and thus titrating its activity during UUO-induced renal fibrosis., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Understanding the adsorption mechanisms of metal cations on the surfaces of solids is important for determining the fate of these metals in water and wastewater treatment. The adsorption kinetic, isothermal, thermodynamic and mechanistic properties of cadmium (Cd(II)) in an aqueous solution containing Mg-Al-CO3- and magnetic Fe3O4/Mg-Al-CO3-layered double hydroxide (LDH) were studied. The results demonstrated that the adsorption kinetic and isotherm data followed the pseudo-second-order model and the Langmuir equation, respectively. The adsorption process of Cd(II) was feasible, spontaneous and endothermic in nature. X-ray diffraction (XRD) and Fourier transform infrared (FTIR) spectroscopy were used to explain the adsorption mechanisms. The characteristic XRD peaks and FTIR bands of CdCO3 emerged in the LDH spectra after Cd(II) adsorption, which indicated that the adsorption of Cd(II) by LDHs occurred mainly via CdCO3 precipitation, surface adsorption and surface complexation. Furthermore, the magnetic Fe3O4/Mg-Al-CO3-LDH can be quickly and easily separated using a magnet before and after the adsorption process., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Apolipoprotein E (ApoE) genotypes are related to clinical presentations in patients with Wilson's disease, indicating that ApoE may play an important role in the disease. However, our understanding of the role of ApoE in Wilson's disease is limited. High copper concentration in Wilson's disease induces excessive generation of free oxygen radicals. Meanwhile, ApoE proteins possess antioxidant effects. We therefore determined whether copper-induced oxidative damage differ in the liver of wild-type and ApoE knockout (ApoE(-/-)) mice. Both wild-type and ApoE(-/-) mice were intragastrically administered with 0.2 mL of copper sulfate pentahydrate (200 mg/kg; a total dose of 4 mg/d) or the same volume of saline daily for 12 weeks, respectively. Copper and oxidative stress markers in the liver tissue and in the serum were assessed. Our results showed that, compared with the wild-type mice administered with copper, TBARS as a marker of lipid peroxidation, the expression of oxygenase-1 (HO-1), NAD(P)H dehydrogenase, and quinone 1 (NQO1) significantly increased in the ApoE(-/-) mice administered with copper, meanwhile superoxide dismutase (SOD) activity significantly decreased. Thus, it is concluded that ApoE may protect the liver from copper-induced oxidative damage in Wilson's disease., (Copyright © 2015 Elsevier Inc. All rights reserved.)

We report here the synthesis of three new nickel(II) complexes: [Ni(PzTA)2CO3]·5H2O (PzTA=2,4-diamino-6-(2'-pyrazin)-1,3,5-triazine) in 1, [NiQ(PyTA)(H2O)2]Cl·H2O (HQ=8-hydroxyquinoline, PyTA=2,4-diamino-6-(2'-pyridyl)-1,3,5-triazine) in 2, [NiQ(PzTA)(H2O)2]Cl·H2O in 3, and they were characterized by UV spectroscopy, elemental analysis, molar conductivity and X-ray single crystal diffraction. Binding of the complexes to ct-DNA was investigated with electronic spectroscopy, ethidium bromide displacement from DNA, viscometry and cyclic voltammetry. The results depicted the DNA binding mode of the three complexes was intercalation, and complex 1 together with external static-electricity. Moreover, the three complexes also presented potential anti-oxidant activity. Interestingly, we found 1 was sensitive to oxygen and to the polarity of nonaqueous solvents in fluorescence spectroscopy. Fluorescence of 2 and 3 is weak in neutral aqueous solvents, but is greatly enhanced by addition of ct-DNA. Thus, 2 and 3 can be used to DNA detection as DNA fluorescence probes with a LOD of 1.61 ng mL(-1), 4.90 ng mL(-1) for the relative wide linear range of 0.01-20 μg mL(-1), 0.02-30 μg mL(-1), respectively. These findings indicate that 1 may be a potential optical probe for oxygen-free environments in nonaqueous form, while 2 and 3 were DNA-targeted probes., (Copyright © 2015 Elsevier B.V. All rights reserved.)