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Background: In Chinese Pharmacopeia, Picrasma quassioides (PQ) stems and leaves are recorded as Kumu with antimicrobial, anti-cancer, anti-parasitic effects, etc. However, thick stems are predominantly utilized as medicine in many Asian countries, with leaves rarely used. By now, the phytochemistry and bioactivity of PQ leaves are not well investigated., Methods: An Orbitrap Elite mass spectrometer was employed to comprehensively investigate PQ stems and leaves sourced from 7 different locations. Additionally, their bioactivities were evaluated against 5 fungi, 6 Gram-positive bacteria and 9 Gram-negative bacteria, a tumor cell line (A549), a non-tumor cell line (WI-26 VA4) and N 2 wild-type Caenorhabditis elegans., Results: Bioassay results demonstrated the efficacy of both leaves and stems against tumor cells, several bacteria and fungi, while only leaves exhibited anthelmintic activity against C. elegans. A total of 181 compounds were identified from PQ stems and leaves, including 43 β-carbolines, 20 bis β-carbolines, 8 canthinone alkaloids, 56 quassinoids, 12 triterpenoids, 13 terpenoid derivatives, 11 flavonoids, 7 coumarins, and 11 phenolic derivatives, from which 10 compounds were identified as indicator components for quality evaluation. Most alkaloids and triterpenoids were concentrated in PQ stems, while leaves exhibited higher levels of quassinoids and other carbohydrate (CHO) components., Conclusion: PQ leaves exhibit distinct chemical profiles and bioactivity with the stems, suggesting their suitability for medicinal purposes. So far, the antibacterial, antifungal, and anthelmintic activities of PQ leaves were first reported here, and considering PQ sustainability, the abundant leaves are recommended for increased utilization, particularly for their rich content of PQ quassinoids., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Atherosclerotic plaque formation is largely attributed to the impaired efferocytosis, which is known to be associated with the pathologic upregulation of cluster of differentiation 47 (CD47), a key antiphagocytic molecule. By gene expression omnibus (GEO) datasets analysis, we identified that four miRNAs are aberrantly downregulated in atherosclerosis, coronary artery disease, and obesity. Of them, hsa-miR-299-3p (miR-299-3p) was predicted to target the 3'UTR of human CD47 mRNA by bioinformatics analysis. Further, we demonstrated that miR-299-3p negatively regulates CD47 expression by binding to the target sequence "CCCACAU" in the 3'UTR of CD47 mRNA through luciferase reporter assay and site-directed mutagenesis. Additionally, we found that miR-299-3p was downregulated by ~32% in foam cells in response to oxidized low-density lipoprotein (ox-LDL) stimulation, thus upregulating CD47 and contributing to the impaired efferocytosis. Whereas, restoration of miR-299-3p reversed the ox-LDL-induced upregulation of CD47, thereby facilitating efferocytosis. In high-fat diet (HFD) fed ApoE -/- mice, we discovered that miR-299-3p was downregulated thus leading to upregulation of CD47 in abdominal aorta. Conversely, miR-299-3p restoration potently suppressed HFD-induced upregulation of CD47 and promoted phagocytosis of foam cells by macrophages in atherosclerotic plaques, thereby reducing necrotic core, increasing plaque stability, and mitigating atherosclerosis. Conclusively, we identify miR-299-3p as a negative regulator of CD47, and reveal a molecular mechanism whereby the ox-LDL-induced downregulation of miR-299-3p leads to the upregulation of CD47 in foam cells thus contributing to the impaired efferocytosis in atherosclerosis, and propose miR-299-3p can potentially serve as an inhibitor of CD47 to promote efferocytosis and ameliorate atherosclerosis., (© 2024 Federation of American Societies for Experimental Biology.)

Peptide-based therapeutics hold immense promise for the treatment of various diseases. However, their effectiveness is often hampered by poor cell membrane permeability, hindering targeted intracellular delivery and oral drug development. This study addressed this challenge by introducing a novel graph neural network (GNN) framework and advanced machine learning algorithms to build predictive models for peptide permeability. Our models offer systematic evaluation across diverse peptides (natural, modified, linear and cyclic) and cell lines [Caco-2, Ralph Russ canine kidney (RRCK) and parallel artificial membrane permeability assay (PAMPA)]. The predictive models for linear and cyclic peptides in Caco-2 and RRCK cell lines were constructed for the first time, with an impressive coefficient of determination ( R 2 ) of 0.708, 0.484, 0.553, and 0.528 in the test set, respectively. Notably, the GNN framework behaved better in permeability prediction with larger data sets and improved the accuracy of cyclic peptide prediction in the PAMPA cell line. The R 2 increased by about 0.32 compared with the reported models. Furthermore, the important molecular structural features that contribute to good permeability were interpreted; the influence of cell lines, peptide modification, and cyclization on permeability were successfully revealed. To facilitate broader use, we deployed these models on the user-friendly KNIME platform (https://github.com/ifyoungnet/PharmPapp). This work provides a rapid and reliable strategy for systematically assessing peptide permeability, aiding researchers in drug delivery optimization, peptide preselection during drug discovery, and potentially the design of targeted peptide-based materials.

Clear cell renal cell carcinoma (ccRCC) is a fatal urological malignancy. Members of the never-in mitosis gene A (NIMA)-related kinase (NEK) family have been found to participate in the progression of several cancers and could be used as target genes to treat corresponding diseases. Nonetheless, the prognostic value and immune infiltration levels of NEK family genes in ccRCC remain unknown. The GSCA, TIMER, and GEPIA databases were utilized to examine the differential expression of NEK family members in ccRCC, and the Kaplan-Meier plotter was utilized to analyze the prognosis. The STRING database was used to construct a protein-protein interaction network. Analysis of function was performed by the Sangerbox tool. In addition, the relationship between NEK family genes and immune cells was explored using the TIMER and TISIDB databases. Finally, we used quantitative real-time PCR (qPCR) and immunohistochemistry (IHC) for experimental verification. Transcriptional levels of NEK2, NEK3, NEK5, NEK6, and NEK11 significantly differed between ccRCC and normal tissues. Moreover, there was a significant correlation between NEK1, NEK2, NEK4, NEK8, NEK9, and NEK10 and their clinicopathological stages in patients with ccRCC. Based on survival analysis, ccRCC patients with high transcriptional levels of NEK2, NEK3, NEK8, and NEK10 and low transcriptional levels of NEK1, NEK4, NEK5, NEK6, NEK7, NEK9, NEK11 had shorter survival times. Additionally, a significant relationship was observed between NEK family members and immune cell infiltration, immune cell markers, and immune subtypes. These results indicate that NEK family members are significantly differentially expressed in ccRCC, and a significant correlation exists between the NEK family and prognosis and immune infiltration. NEK family members may act as therapeutic targets and prognostic indicators in ccRCC., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Somatic mutations have been observed to induce aldosterone-producing adenomas (APAs). These may be accelerated during pregnancy. Somatic PRKACA mutations are common in cortisol-producing adenomas (CPAs). However, their role in APAs, particularly aldosterone- and cortisol-producing adenomas (A/CPAs), is not well understood. This study aims to investigate the association between PRKACA mutations and the accelerated development of A/CPAs during pregnancy., Case Presentation: A patient with primary aldosteronism (PA) associated with severe Cushing's syndrome (CS) underwent surgical resection of an adrenal tumor one year after delivery. Pathologic examination revealed an adrenocortical adenoma characterized primarily by zona glomerulosa hyperplasia. Somatic mutation analysis revealed the presence of the somatic PRKACA mutation, which was validated as a deleterious mutation by various computational databases. Immunohistochemical results showed positive staining for cytochrome P450 family 11 subfamily B member 1 (CYP11B1), cytochrome P450 family 11 subfamily B member 2 (CYP11B2), and luteinizing hormone/chorionic gonadotropin receptor (LHCGR). Our study included a review of 20 previously documented cases of aldosterone- and cortisol-producing adenomas (A/CPAs), two of which were concurrently positive for both CYP11B1 and CYP11B2, consistent with our findings., Conclusion: Somatic mutations in PRKACA may correlate with the upregulation of LHCGR, which synergistically drives the accelerated growth of co-secretion tumors during pregnancy, thereby exacerbating disease progression., (© 2024. The Author(s).)

Type 3 resistant starch from Canna edulis (Ce-RS3) is an insoluble dietary fiber which could improve blood lipids in animals, but clinically robust evidence is still lacking. We performed a double-blind randomized controlled trial to assess the effects of Ce-RS3 on lipids in mild hyperlipidemia. One hundred and fifteen patients were included followed the recruitment criteria, and were randomly allocated to receive Ce-RS3 or placebo (native starch from Canna edulis) for 12 weeks (20 g/day). In addition to serum lipids, complete blood counts, serum inflammatory factors, antioxidant indexes, and dietary survey, 16 S rRNA sequencing technique was utilized to analyze the gut microbiota alterations. Targeted quantitative metabolomics (TQM) was used to detect metabolite changes. Compared with the placebo, Ce- RS3 significantly decreased levels of total cholesterol, lowdensity lipoprotein cholesterol, and non-high-density lipoprotein cholesterol, and increased the glutathione peroxidase. Based on the 16 S rRNA sequencing, TQM, the correlation analysis, as well as the Kyoto Encyclopedia of Genes (KEGG) and Genomes and Human Metabolome Database (HMDB) analysis, we found that Ce-RS3 could increase the abundances of genera Faecalibacterium and Agathobacter, while reduce the abundances of genera norank_f_Ruminococcaceae and Christensenellaceae_R-7_ group to regulate phenylalanine metabolism, which could reduce the fatty acid biosynthesis and fatty acid elongation in the mitochondria to lower blood lipids. Conclusively, we firstly confirmed the feasibility of Ce-RS3 for clinical application, which presents a novel, effective therapy for the mild hyperlipidemia. (Chictr. org. cn. Clinical study on anti-mild hyperlipidemia of Canna edulis RS3 resistant starch, ID Number: ChiCTR2200062871)., 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. Published by Elsevier Ltd.)

Excessive reactive oxygen species (ROS) in the microenvironment of osteoporosis (OP) not only accelerate the bone absorption, but also affect the osteogenic and mineralized effect of osteoblasts. Procyanidins (PC) have been reported to have anti-oxidation effects, but low bioavailability. This study aimed to explore the effect of magnesium oxide nanoparticles (MgO-PC NPs)-loaded PC on the osteogenesis and mineralization of osteoblasts that stimulated by H 2 O 2 . PC was loaded onto MgO NPs and characterized by transmission electron microscopy, energy dispersive spectroscopy, dynamic light scattering, and Fourier transform infrared spectroscopy. After primary screening by cytotoxicity assay, MgO-PC NPs containing 20 μM of PC were chosen for further studies. In H 2 O 2 -stimulated osteoblasts, dichlorodihydrofluorescein diacetate probe, Cell Counting Kit-8, quantitative real-time polymerase chain reaction, alkaline phosphatase staining/activity and Alizarin red staining were used to detect the ROS production, cell viability and osteogenic and mineralized markers of osteoblasts. PC was loaded onto MgO NPs to successfully receive MgO-PC NPs with a diameter of about 144 nm and negative potential. PC can sustain release from MgO-PC NPs for at least 16 d. The controlled release of PC from MgO-PC NPs can effectively eliminate ROS and thereby promoted the cell activity. Most importantly, the osteogenesis and mineralization of osteoblasts under oxidative stress were also significantly reversed by MgO-PC NPS. Thus, these findings indicate that MgO-PC NPs may be developed as a potential therapeutic strategy for OP., (© 2024 IOP Publishing Ltd.)

Immunoevasion has been a severe obstacle for the clinical treatment of breast cancer (BC). CD47, known as an anti-phagocytic molecule, plays a key role in governing the evasion of tumor cells from immune surveillance by interacting with signal-regulated protein α (SIRPα) on macrophages. Here, we report for the first time that miR-299-3p is a direct regulator of CD47 with tumor suppressive effects both in vitro and in vivo. miRNA expression profiles and overall survival of BC cohorts from the Cancer Genome Atlas, METABRIC, or GSE19783 datasets showed that miR-299-3p is downregulated in BC tissues and that BC patients with low levels of miR-299-3p have poorer prognoses. Using dual-luciferase reporter, qRT-PCR, Western blot, and phagocytosis assays, we proved that restoration of miR-299-3p can suppress CD47 expression by directly targeting the predicted seed sequence "CCCACAU" in its 3'-UTR, leading to phagocytosis of BC cells by macrophages, whereas miR-299-3p inhibition or deletion reversed this effect. Additionally, Gene Ontology (GO) analysis and a variety of confirmatory experiments revealed that miR-299-3p was inversely correlated with cell proliferation, migration, and the cell cycle process. Mechanistically, miR-299-3p can also directly target ABCE1, an essential ribosome recycling factor, alleviating these malignant phenotypes of BC cells. In vivo BC xenografts based on nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice further proved that restoration of miR-299-3p resulted in a significant suppression of tumorigenesis and a promotion of macrophage activation and infiltration. Overall, our study suggested that miR-299-3p is a potent inhibitor of CD47 and ABCE1 to exhibit bifunctional BC-suppressing effects through immune activation conjugated with malignant behavior inhibition in breast carcinogenesis and thus can potentially serve as a novel therapeutic target for BC., 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.)

Although human pluripotent stem cell (PSC)-derived brain organoids have enabled researchers to gain insight into human brain development and disease, these organoids contain solely ectodermal cells and are not vascularized as occurs during brain development. Here it is created less complex and more homogenous large neural constructs starting from PSC-derived neuroprogenitor cells (NPC), by fusing small NPC spheroids into so-called concentroids. Such concentroids consisted of a pro-angiogenic core, containing neuronal and outer radial glia cells, surrounded by an astroglia-dense outer layer. Incorporating PSC-derived endothelial cells (EC) around and/or in the concentroids promoted vascularization, accompanied by differential outgrowth and differentiation of neuronal and astroglia cells, as well as the development of ectodermal-derived pericyte-like mural cells co-localizing with EC networks. Single nucleus transcriptomic analysis revealed an enhanced neural cell subtype maturation and diversity in EC-containing concentroids, which better resemble the fetal human brain compared to classical organoids or NPC-only concentroids. This PSC-derived "vascularized" concentroid brain model will facilitate the study of neurovascular/blood-brain barrier development, neural cell migration, and the development of effective in vitro vascularization strategies of brain mimics., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive and fatal neurodegenerative disorder, characterized by selective loss of motor neurons (MNs). A number of causative genetic mutations underlie the disease, including mutations in the fused in sarcoma (FUS) gene, which can lead to both juvenile and late-onset ALS. Although ALS results from MN death, there is evidence that dysfunctional glial cells, including oligodendroglia, contribute to neurodegeneration. Here, we used human induced pluripotent stem cells (hiPSCs) with a R521H or a P525L mutation in FUS and their isogenic controls to generate oligodendrocyte progenitor cells (OPCs) by inducing SOX10 expression from a TET-On SOX10 cassette. Mutant and control iPSCs differentiated efficiently into OPCs. RNA sequencing identified a myelin sheath-related phenotype in mutant OPCs. Lipidomic studies demonstrated defects in myelin-related lipids, with a reduction of glycerophospholipids in mutant OPCs. Interestingly, FUS R521H OPCs displayed a decrease in the phosphatidylcholine/phosphatidylethanolamine ratio, known to be associated with maintaining membrane integrity. A proximity ligation assay further indicated that mitochondria-associated endoplasmic reticulum membranes (MAM) were diminished in both mutant FUS OPCs. Moreover, both mutant FUS OPCs displayed increased susceptibility to ER stress when exposed to thapsigargin, and exhibited impaired mitochondrial respiration and reduced Ca 2+ signaling from ER Ca 2+ stores. Taken together, these results demonstrate a pathological role of mutant FUS in OPCs, causing defects in lipid metabolism associated with MAM disruption manifested by impaired mitochondrial metabolism with increased susceptibility to ER stress and with suppressed physiological Ca 2+ signaling. As such, further exploration of the role of oligodendrocyte dysfunction in the demise of MNs is crucial and will provide new insights into the complex cellular mechanisms underlying ALS., (© 2024. The Author(s).)

Microwave-absorbing materials adapting to high temperatures and harsh environments are in great demand. Herein, a core-shelled Ti 3 AlC 2 @La 2 Zr 2 O 7 (TAC@LZO) composite was designed and fabricated by encapsulating the La 2 Zr 2 O 7 (LZO) thermal insulation ceramic on the surface of highly conductive Ti 3 AlC 2 (TAC) via chemical coprecipitation and subsequent heat treatment. The continuous LZO ceramic coating on the surface improved the oxidation resistance of the composite at 600 °C and modulated its dielectric properties. The TAC@LZO composite exhibited an excellent microwave absorption performance within the temperature range of 25-600 °C, minimum reflection loss (RL min ) < -55 dB, and effective absorption bandwidth (EAB, RL < -10 dB) of 4 GHz. This work presents an effective approach for developing stable high-temperature microwave absorbers from thermal insulation ceramics.

Cardamine circaeoides Hook.f. & Thomson (CC), a herb of the genus Cardamine (family Brassicaceae), has a rich historical usage in China for both culinary and medicinal purposes. It is distinguished by its remarkable ability to hyperaccumulate selenium (Se). CC has demonstrated efficacy in the prevention of metabolic disorders. However, investigations into the effects of CC on asymptomatic hyperuricemia remain scarce. The objective of this study is to elucidate the mechanism by which CC aqueous extract (CCE) exerts its anti-hyperuricemic effects on asymptomatic hyperuricemic rats induced by potassium oxonate (PO) by integrating metabolomics and network pharmacological analysis. Asymptomatic hyperuricemia was induced by feeding rats with PO (1000 mg/kg) and CCE (0.75, 1.5, or 3 g/kg) once daily for 30 days. Various parameters, including body weight, uric acid (UA) levels, histopathology of renal tissue, and inflammatory factors (IL-1β, IL-6, IL-8, and TNF-α) were assessed. Subsequently, metabolomic analysis of kidney tissues was conducted to explore the effects of CCE on renal metabolites and the related pathways. Furthermore, network pharmacology was employed to explicate the mechanism of action of CCE components identified through UPLC-Q-TOF-MS analysis. Finally, metabolomic and network-pharmacology analyses were performed to predict crucial genes dysregulated in the disease model and rescued by CCE, which were then subjected to verification by RT-qPCR. The findings revealed that CCE significantly inhibited the UA levels from the 21st day to the 30th day. Moreover, CCE exhibited significant inhibition of IL-1β, IL-6, IL-8, and TNF-α levels in renal tissues. The dysregulation of 18 metabolites and the tyrosine, pyrimidine, cysteine, methionine, sphingolipid, and histidine metabolism pathways was prevented by CCE treatment. A joint analysis of targets predicted using the network pharmacology approach and the differential metabolites found in metabolics predicted 8 genes as potential targets of CCE, and 3 of them (PNP gene, JUN gene, and ADA gene) were verified at the mRNA level by RT-qPCR. We conclude that CCE has anti-hyperuricemia effects and alleviates renal inflammation in a rat model of hyperuricemia, and these efficacies are associated with the reversal of increased ADA, PNP, and JUN mRNA expression in renal tissues., 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 © 2023 Zhu, Di, Li, Liang, Liu, Nuermaimaiti, Fei, Wang, Wang and Zhang.)

As a chronic inflammatory disease, rheumatoid arthritis (RA) can cause progressive damage to joints and various organs. Hydrogen peroxide plays a significant role in the pathogenesis and progression of RA and thus serves as a biomarker for diagnosing this disease. Although fluorescent probes have emerged as promising tools for detecting H 2 O 2 , most available ones suffer from the aggregation-caused quenching (ACQ) effect, short-wavelength emission, low sensitivity, and poor water solubility. Herein, a new type of "turn-on" AIE probe based on excited state intramolecular proton transfer (ESIPT) was developed, with phenylboronic acid pinacol ester-appended quinolinium as the H 2 O 2 recognition site, which is in the quenched state due to the twisted intramolecular charge transfer (TICT) effect. The probe HTQ-R exhibits good water solubility, high sensitivity, a low detection limit (210 nM), rapid response ability, and good biocompatibility towards hydrogen peroxide, and has shown the ability to accurately target mitochondria. Furthermore, HTQ-R was successfully used to detect exogenous and endogenous hydrogen peroxide in living cells, which enabled real-time monitoring of H 2 O 2 in RA mice, demonstrating its potential significance in the diagnosis and treatment of RA.

Respiratory viral infections, such as coronavirus disease of 2019 (COVID-19) and influenza, cause significant morbidity and mortality and have become a worldwide public health concern with tremendous economic and societal burdens. Vaccination is a major strategy for preventing infections. However, some new vaccines have an unmet need for impairing responses in certain individuals, especially COVID-19 vaccines, despite ongoing vaccine and adjuvant research. Here, we evaluated the effectiveness of Astragalus polysaccharide (APS), a bioactive polysaccharide extracted from the traditional Chinese herb Astragalus membranaceus as an immune adjuvant to regulate the efficacy of influenza split vaccine (ISV) and recombinant severe acute respiratory syndrome (SARS)-Cov-2 vaccine in mice. Our data indicated that APS as an adjuvant can facilitate the induction of high levels of hemagglutination inhibition (HAI) titer and specific antibody immunoglobulin G (IgG) and confer protection against the lethal challenge of influenza A viruses, including increased survival and amelioration of weight loss in mice immunized with the ISV. RNA sequencing (RNA-seq) analysis revealed that the NF-κB and Fc gamma R-mediated phagocytosis signaling pathways are essential for the immune response of mice immunized with the recombinant SARS-Cov-2 vaccine (RSV). Another important finding was that bidirectional immunomodulation of APS on cellular and humoral immunity was observed, and APS-adjuvant-induced antibodies persisted at a high level for at least 20 weeks. These findings suggest that APS is a potent adjuvant for influenza and COVID-19 vaccines, and has the advantages of bidirectional immunoregulation and persistent immunity., 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 The Authors. Published by Elsevier B.V. All rights reserved.)

Uncontrolled angiogenesis is a common denominator underlying many deadly and debilitating diseases such as myocardial infarction, chronic wounds, cancer, and age-related macular degeneration. As the current range of FDA-approved angiogenesis-based medicines are far from meeting clinical demands, the vast reserve of natural products from traditional Chinese medicine (TCM) offers an alternative source for developing pro-angiogenic or anti-angiogenic modulators. Here, we investigated 100 traditional Chinese medicine-derived individual metabolites which had reported gene expression in MCF7 cell lines in the Gene Expression Omnibus (GSE85871). We extracted literature angiogenic activities for 51 individual metabolites, and subsequently analysed their predicted targets and differentially expressed genes to understand their mechanisms of action. The angiogenesis phenotype was used to generate decision trees for rationalising the poly-pharmacology of known angiogenesis modulators such as ferulic acid and curculigoside and validated by an in vitro endothelial tube formation assay and a zebrafish model of angiogenesis. Moreover, using an in silico model we prospectively examined the angiogenesis-modulating activities of the remaining 49 individual metabolites. In vitro , tetrahydropalmatine and 1 beta-hydroxyalantolactone stimulated, while cinobufotalin and isoalantolactone inhibited endothelial tube formation. In vivo , ginsenosides Rb3 and Rc, 1 beta-hydroxyalantolactone and surprisingly cinobufotalin, restored angiogenesis against PTK787-induced impairment in zebrafish. In the absence of PTK787, deoxycholic acid and ursodeoxycholic acid did not affect angiogenesis. Despite some limitations, these results suggest further refinements of in silico prediction combined with biological assessment will be a valuable platform for accelerating the research and development of natural products from traditional Chinese medicine and understanding their mechanisms of action, and also for other traditional medicines for the prevention and treatment of angiogenic diseases., 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 © 2023 Zhu, Yang, Han, Mervin, Hosseini-Gerami, Li, Wright, Trapotsi, Liu, Fan and Bender.)

Background: Pancreatic cancer is one of the most lethal cancers worldwide. Aidi injection (ADI) is a representative antitumor medication based on Chinese herbal injection, but its antitumor mechanisms are still poorly understood., Materials and Methods: In this work, the subcutaneous xenograft model of human pancreatic cancer cell line Panc-1 was established in nude mice to investigate the anticancer effect of ADI in vivo. We then determined the components of ADI using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS) and explored the possible molecular mechanisms against pancreatic cancer using network pharmacology., Results: In vivo experiments, the volume, weight, and degree of histological abnormalities of implanted tumors were significantly lower in the medium and high concentration ADI injection groups than in the control group. Network pharmacology analysis identified four active components of ADI and seven key targets, TNF, VEGFA, HSP90AA1, MAPK14, CASP3, P53 and JUN. Molecular docking also revealed high affinity between the active components and the target proteins, including Astragaloside IV to P53 and VEGFA, Ginsenoside Rb1 to CASP3 and Formononetin to JUN., Conclusion: ADI could reduce the growth rate of tumor tissue and alleviate the structural abnormalities in tumor tissue. ADI is predicted to act on VEGFA, P53, CASP3, and JUN in ADI-mediated treatment of pancreatic cancer., (© 2023. The Author(s).)

Echinacea purpurea (L.) Moench (EP) is a well-known botanical supplement with antioxidant characteristics. However, the effects of EP on oxidative stress induced by hyperthyroidism have not yet been studied. This study was designed to evaluate the antioxidative effect of ethanolic Echinacea Purpurea (EEP) on hyperthyroidism-induced oxidative stress mice using an integrated strategy combining transcriptomics with network pharmacology analysis. Firstly, a hyperthyroidism mice model was induced via thyroxine (160 mg/kg) and EEP (1, 2, or 4 g/kg) once daily for 2 weeks. Body weight, thyroid-stimulating hormones, and oxidative stress markers were tested. Secondly, EEP regulating the potential genes at transcript level were analyzed. Thirdly, a network pharmacology based on the constituents of EEP identified using UPLC-Q-TOF-MS analysis was adopted. Finally, a joint analysis was performed to identify the key pathway. The results showed that EEP significantly changed the thyroid-stimulating hormones and oxidative stress markers. Meanwhile, RT-qPCR and Western Blotting demonstrated that the mechanism of the antioxidant effect of EEP reversed the mRNA expression of EHHADH, HMGCR and SLC27A2 and the protein expression of FABP and HMGCR in AMPK and PPAR signaling pathways. This study integrates transcriptomics with network pharmacology to reveal the mechanism of ameliorative effect of EEP on hyperthyroidism-induced oxidative stress.

In order to reduce the sintering temperature and improve the mechanical properties of B4C ceramics, ZrB2 was formed in situ using the SPS sintering method with ZrO2 and B4C as raw materials. Thermodynamic calculations revealed that CO pressure affected the formation of ZrB2 at temperatures from 814 °C to 1100 °C. The experimental results showed that the ZrB2 grain size was <5 µm and that the grains were uniformly distributed within the B4C ceramics. With an increase in ZrO2 content, the Vickers hardness and flexural strength of the B4C ceramics first increased and then decreased, while the fracture toughness continuously increased. When the content of ZrO2 was 15 wt%, the Vickers hardness, fracture toughness and flexural strength of B4C ceramics were 35.5 ± 0.63 GPa, 3.6 ± 0.24 MPa·m1/2 and 403 ± 10 MPa, respectively. These results suggest that ZrB2 inhibits B4C grain growth, eliminates crack tip stress, and provides fine grain to strengthen and toughen B4C ceramics.

Lepidium meyenii Walp. (Maca), as a natural food supplement, has strong antioxidant and energy metabolism-improving characteristics, and Maca polysaccharide (MP) is its effective component. MP has been shown to mitigate liver damage in previous research, and Cyclophosphamide (CYP)-induced hepatotoxicity is also a major concern in clinical practice. We investigated the possible cytoprotective effect of MP on CYP-induced liver injury, and explored its underlying mechanism by analyzing the resulting liver metabolic profiles. MP significantly inhibited increases in serum transaminase, improved pathological changes, reduced oxidative stress, and increased the levels of energy metabolism-related enzymes. Metabolomic analysis showed that MP corrected lipid metabolic problems and regulated the pentose phosphate pathway and acid metabolism, thereby protecting against apoptosis of hepatocytes. The Pearson correlation analysis indicated that antioxidant enzymes and energy metabolism-related enzymes are closely correlated with these differential metabolites. In addition, the upstream Keap1-Nrf2 antioxidant signal transduction pathway was explored to validate the possible mechanism of the cytoprotective effect of MP. In conclusion, MP plays a protective role in CYP-induced hepatotoxicity through these potential metabolic means, where it ameliorates oxidative stress, improves energy metabolism, and restores mitochondrial respiration by regulating the Keap1-Nrf2 signaling pathway, thereby preventing liver damage.

Introduction: Functional constipation (FC) is a common functional gastrointestinal disease and is one of the most common outpatient diseases. The purpose of this study was to investigate the efficacy and safety of the traditional Chinese medicine Besunyen Detox Tea (BDT) for FC and to compare the effect of BDT between constipation patients with and non-dryness-heat syndrome., Methods and Analysis: This multicenter, prospective, observational registry study included 1000 participants diagnosed with FC. This study will collaborate with 3 comprehensive hospitals and 15 community hospitals and recruit patients into the registry between July 2022 and July 2023. After enrollment, we will collect the individual characteristics of each patient, anthropometric data and general condition, bowel movement, patient assessment of constipation symptoms, patient assessment of constipation quality of life, TCM syndrome scale, and time to take the laxative product again after treatment. We will also record adverse events and economic indicators at each visit., Discussion: This is the first registry-based study to collect real-world data of participants diagnosed with FC receiving BDT treatment. The results of this registry may also reflect these characteristics and provide direct clinical evidence to verify the importance of syndrome differentiation and treatment for the use of TCM health care products., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Oxidative stress and memory impairment have been implicated as common functional brain diseases. Nuclear factor E2-related factor 2 (Nrf2) is highly induced in oxidative stress, indicating that Nrf2 is an emerging target of memory therapy. This study aimed to investigate the effect of noni on brain memory impairment induced by hydrocortisone and its protective mechanism in mice., Methods: Male Kunming mice ( n  = 8/group) were given hydrocortisone by gastric gavage for 14 consecutive days to establish the memory impairment model, except for those in the control group. On the same day, the corresponding drugs were given by gastric gavage. The changes in ethology were examined. The brains were extracted and subjected to western blot analysis and biochemical analyses to assess the activities of antioxidative stress., Results: The middle- and high-dose noni groups exhibited ameliorated ethology, and the high-dose noni group exhibited increased cerebral protein expression of Nrf2, Kelch-like ECH-associated protein 1 (KEAP1), and haem oxygenase-1 (HO-1) compared to the model group. The arrangement of CA3 vertebral cells in the hippocampus of mice was slightly compact, and hyperchromasia and pyknosis were alleviated. Furthermore, biochemical analyses showed that the activities of enzymes related to oxidative stress in the high-dose noni group were increased., Conclusions: Noni might be a powerful antioxidant that can protect nerve cells and may possess potential benefits for the treatment of memory impairment., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Rui Zhang et al.)

Mental health has become a new challenge in cancer treatment, with a high prevalence of depression in patients with cancer. Albiflorin (AF) and paeoniflorinn (PF) are isomers extracted from the root of Paeoniae Radix Alba (Baishao in Chinese), belonging to the monoterpene glycosides, and multiple studies have been conducted on their antidepression and anti-cancer effects. However, the effects of AF and PF on cancer-related depression are unclear. Therefore, the current study aims to investigate whether the two isomers are able to exert antidepressant-like effects and understand the underlying mechanisms in a rat model, established by combining irradiation with chronic restraint stress and solitary confinement. Our results demonstrate a significant regulation of AF and PF in the pharmacodynamic index, including the peripheral blood, organ index, behavioral traits, and HPA axis, relative to control rats. In serum and cerebral cortex metabonomics analysis, AF and PF showed a significantly restorative trend in abnormal biomarkers and regulating ether lipid metabolism, alanine, aspartate, glutamate metabolism, tryptophan metabolism, carnitine metabolism, arachidonic acid metabolism, arginine and proline metabolism pathway. Eight potential biomarkers were further screened by means of receiver operating characteristic (ROC) analysis. The data indicate that AF and PF could effectively ameliorate a depression-like state in the model rats, and the mechanism may be associated with the regulation of the neuroendocrine immune system and disrupted metabolic pathways. Further experiments are warranted to comprehensively evaluate the antidepressant effects of AF and PF in cancer-related depression. This study provides a better insight into the action mechanisms of antidepression of TCM, and provides a new perspective for the therapy of cancer-related depression., 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 conflictof interest., (Copyright © 2022 Zhao, Zhang, Zhu, He, Fei, Yue, Wang and Wang.)

With the increasing popularity of herbal medicine, high standards of the high quality control of herbs becomes a necessity, with the herb recognition as one of the great challenges. Due to the complicated processing procedure of the herbs, methods of manual recognition that require chemical materials and expert knowledge, such as fingerprint and experience, have been used. Automatic methods can partially alleviate the problem by deep learning based herb image recognition, but most studies require powerful and expensive computation hardware, which is not friendly to resource-limited settings. In this paper, we introduce a deep learning-enabled mobile application which can run entirely on common low-cost smartphones for efficient and robust herb image recognition with a quite competitive recognition accuracy in resource-limited situations. We hope this application can make contributions to the increasing accessibility of herbal medicine worldwide., (© 2022. The Author(s).)

Background: Breast cancer is the leading cause of cancer death in women. The current methods of chemotherapy for breast cancer generally have strong adverse reactions and drug resistance. Therefore, the discovery of novel anti-breast cancer lead compounds is urgently needed., Objective: This study aimed to design and synthesize a series of 2-alkyl substituted fluorinated genistein analogues and evaluate their anti-breast cancer activity., Methods: Target compounds were obtained in a multistep reaction synthesis. The anti-tumor activity of compounds I-1~I-35 was evaluated with MCF-7, MDA-MB-231, MDA-MB-435, and MCF-10A cell lines in vitro, with tamoxifen as the positive control. Molecular docking was used to study the interaction between the synthesized compounds and PI3K-gamma., Results: A series of 2-alkyl substituted fluorinated genistein analogues was designed, synthesized, and screened for their bioactivity. Most of the compounds displayed better selectivity toward breast cancer cell lines as compared to tamoxifen. Among these analogues, I-2, I-3, I-4, I-9, I-15, and I-17 have the strongest selective inhibition of breast cancer cells. Compounds I-10, I-13, I-15, I-17, and I- 33 were found to have significant inhibitory effects on breast cancer cells. Molecular docking studies have shown that these compounds may act as PI3Kγ inhibitors and may further exhibit anti-breast cancer effects., Conclusion: Most of the newly synthesized compounds could highly, selectively inhibit breast cancer cell lines. The experimental results indicate that the synthesized analogs may also have obvious selective inhibitory effects on other malignant proliferation cancer cells., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Polymer-derived SiBCN ceramics (PDCs-SiBCN) are promising ultrahigh-temperature ceramics owing to their excellent high-temperature oxidation resistance and electromagnetic wave (EMW)-absorbing capability. In this paper, the microstructure evolutions, the dielectric properties, and EMW absorption properties of Y 2 O 3 -doped SiBCN ceramics were investigated. The results reveal that Y 2 O 3 acting as a catalyst promotes the formation of SiC, BN(C), and graphite crystalline phases in the SiBCN ceramics, and these crystalline phases are constructed as conduction phases and polarization phases to enhance the EMW-adsorbing properties. The minimum reflection loss (RL min ) reaches -42.22 dB at 15.28 GHz, and the effective absorption bandwidth is 4.72 GHz (13.28-18.00 GHz). In addition, there is only 0.56 wt % mass loss for the Y 2 O 3 -doped SiBCN ceramics when they are heated from ambient temperature to 1500 °C in air, indicating that the Y 2 O 3 -doped SiBCN ceramics obtain excellent oxidation resistance at high temperature. We believe that rare metal oxidation is beneficial for the growth of crystalline phases in the PDCs, resulting in high EMW-absorbing properties and oxidation resistance. Thus, the research extends a novel method and design strategy for microstructure regulation and property enhancement of PDCs.

Coupling between the surface and near-bottom currents in the Gulf of Mexico (GoM) has been reported in many case studies. However, geographical variations of this coupling need more examination. In this study, surface geostrophic currents derived from satellite-observed sea surface height and subsurface currents from a collection of deep ocean moorings are used to examine the surface and bottom coupling in different parts of the GoM. The short-period (30-90 days) fluctuations generated by the Loop Current (LC) and the LC eddies (LCEs) have a more vertically coherent structure and stronger deep ocean expressions than the long-period fluctuations (>90 days). In addition, the strength of the coupling is modulated by the long-period variations of the LC and LCE sheddings. Moreover, the surface and bottom coupling varies geographically. In the LC region, the surface fluctuations along the eastern side of the LC are important in causing the bottom current fluctuations through baroclinic instability under the LC and through traveling topographic Rossby waves (TRWs) north of the LC. In the central deep GoM, the bottom currents are affected by the upper fluctuations of the northern LC through both local baroclinic instability and remote TRW propagation. In the northwestern GoM, the bottom current fluctuations are largely related to the remote surface variability from the west side of the LC by TRWs propagating northwestward. This study will help us better understand mechanisms of the bottom current fluctuations that are important for the dispersal of deep ocean materials and properties., (©2020. The Authors.)

Compound Kushen injection (CKI), a medicine in widespread clinical use in China, has proven therapeutic effects on cancer. However, few molecular mechanism analyses have been carried out. To address this problem, bioinformatics approaches combining weighted gene co-expression network analysis with network pharmacology methods were undertaken to elucidate the underlying molecular mechanisms of CKI in the treatment of esophageal cancer (ESCA). First, the key gene modules related to the clinical traits of ESCA were analysed by WCGNA. Based on the results, the hub genes related to CKI treatment for ESCA were explored through network pharmacology. Molecular docking simulation was performed to recognize the binding activity of hub genes with CKI compounds. The results showed that the potential hub targets, including EGFR, ErbB2, CCND1 and IGF1R, are therapeutic targets of CKI for the treatment of ESCA. Moreover, these targets were significantly enriched in many pathways related to cancer and signalling pathways, such as the PI3K-Akt signalling pathway and ErbB signalling pathway. In conclusion, this research partially highlighted the molecular mechanism of CKI in the treatment of ESCA, offering great potential in the identification of the effective compounds in CKI and biomarkers for ESCA treatment.

Background: As an effective prescription for gastric cancer (GC), Compound Kushen Injection (CKI) has been widely used even though few molecular mechanism analyses have been carried out., Methods: In this study, we identified 16 active ingredients and 60 GC target proteins. Then, we established a compound-predicted target network and a GC target protein-protein interaction (PPI) network by Cytoscape 3.5.1 and systematically analyzed the potential targets of CKI for the treatment of GC. Finally, molecular docking was applied to verify the key targets. In addition, we analyzed the mechanism of action of the predicted targets by Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses., Results: The results showed that the potential targets, including CCND1, PIK3CA, AKT1, MAPK1, ERBB2, and MMP2, are the therapeutic targets of CKI for the treatment of GC. Functional enrichment analysis indicated that CKI has a therapeutic effect on GC by synergistically regulating some biological pathways, such as the cell cycle, pathways in cancer, the PI3K-AKT signaling pathway, the mTOR signaling pathway, and the FoxO signaling pathway. Moreover, molecular docking simulation indicated that the compounds had good binding activity to PIK3CA, AKT1, MAPK1, ERBB2, and MMP2 in vivo., Conclusion: This research partially highlighted the molecular mechanism of CKI for the treatment of GC, which has great potential in the identification of the effective compounds in CKI and biomarkers to treat GC.

Background: Considering the limitations of conventional western treatment for community-acquired pneumonia (CAP) and the extensive exploration of Chinese herbal injections (CHIs), systematically and critically evaluating the efficacy of CHIs in the treatment of CAP is necessary., Purpose: This study constructed a network meta-analysis (NMA) to investigate the efficacy of CHIs (including the Reduning injection (RDN), Yanhuning injection (YHN), Xiyanping injection (XYP), and Tanreqing injection (TRQ)) combined with Western medicine (WM) and WM alone in CAP., Methods: A literature review was conducted in several databases from inception to June 2018. The quality of the included studies was assessed by the Cochrane risk of bias tool and modified Jadad scale. Data were analyzed by STATA 13.0 and WinBUGS 14.0 software. Surface under the cumulative ranking curve (SUCRA) probability values were applied to rank the examined treatments. Clustering analysis was utilized to compare the effect of CHIs between two different outcomes., Results: A total of 47 eligible randomized controlled trials involving 4713 patients and 4 CHIs were included. The results of the NMA showed that RDN, YHN, XYP and TRQ combined with WM significantly improved treatment performance compared to WM alone. YHN+WM had obvious superiorities in the clinical effective rate, time for the disappearance of cough and the level of C-reactive protein. TRQ+WM was the most advantageous in shortening the time for defervescence and the average hospitalization time. XYP+WM was shown to reduce the time for the disappearance of lung rales best. Sixteen articles reported adverse drug reactions/adverse drug events (ADRs/ADEs) in detail, and 17 articles reported that there were no obvious ADRs/ADEs., Conclusion: This NMA showed that using CHIs in combination with WM improved treatment performance and could be beneficial for patients with CAP compared to using WM alone. Thereinto, YHN+WM showed a preferable improvement on patients with CAP when unified considering the clinical effective rate and other outcomes. As for safety, more evidence is needed to support this hypothesis., (Copyright © 2019 The Authors. Published by Elsevier GmbH.. All rights reserved.)

In order to solve the problem that bolts in traditional packaged direct methanol fuel cells (DMFCs) take up a large area and reduce the specific energy (energy per unit weight) and power density (power per unit area), a new button-type micro direct methanol fuel cell (B-μDMFC) is designed, assembled, and packaged. The cell with four different structures was tested before and after packaging. The results indicate that the button cell with three-dimensional graphene and springs has the best performance. The equivalent circuit and methanol diffusion model was applied to explain the experimental results. The peak volumetric specific power density of the cell is 11.85 mW cm -3 . This is much higher than traditional packaged DMFC, because the novel B-μDMFC eliminates bolts in the structure and improves the effective area ratio of the cell., Competing Interests: The authors declare no conflict of interest.

The present study aimed to investigate the therapeutic effects of Euterpe oleracea Mart. (EO) on alcoholic liver diseases (ALD). A total of 30 Wistar rats were randomly divided into three groups (10 rats per group), including alcohol group (alcohol intake), EO group (alcohol + EO puree intake) and control group (distilled water intake). The activity of superoxide dismutase (SOD) and alkaline phosphatase (ALP), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and the levels of cholesterol (CHO), triglyceride (TG), malondialdehyde (MDA) and glutathione (GSH) in the serum as well as the liver tissue levels of interleukin 8 (IL-8), tumor necrosis factor-α (TNF-α) and transforming growth factor-β (TGF-β) were measured. Histopathological changes in liver tissues were observed by hematoxylin and eosin staining. Reverse-transcription quantitative PCR analysis was performed for detecting the expression of nuclear factor (NF)-κB and CD68. The results indicated that EO intake significantly decreased ALT, AST, ALP, TG and CHO as well as the hepatic index in alcohol-treated rats. In addition, EO treatment relieved alcohol-induced oxidative stress by decreasing the levels of MDA and TG, and increasing the activity of SOD and GSH levels. In addition, the expression of TNF-α, TGF-β, IL-8, NF-κB and CD-68 in the liver were decreased by EO treatment. Furthermore, EO intake alleviated the histopathological liver damage, including severe steatosis and abundant infiltrated inflammatory cells. In conclusion, EO alleviated alcohol-induced liver injury in rats by alleviating oxidative stress and inflammatory response.

1. Polymorphisms of cytochrome P450 2C19 (CYP2C19) is an important factor contributing to variability of voriconazole pharmacokinetics. Polymorphisms of CYP3A4, CYP3A5, CYP2C9 and non-genetic factors such as age, gender, body mass index (BMI), transaminase levels, concomitant medications might also affect voriconazole initial steady serum trough concentration (VIC min ) in haematological patients, but the effects were not clear. 2. Eighteen single-nucleotide polymorphisms in CYP2C19, CYP3A4, CYP3A5, CYP2C9 were genotyped. Patients were stratified into two groups according to CYP2C19 genotype. Group 1 were patients with CYP2C19*2 or CYP2C19*3, and Group 2 were homozygous extensive metabolizers. The effects were studied in different groups. VIC min was adjusted on daily dose (VIC min /D) for overcoming effect of dose. 3. A total of 106 blood samples from 86 patients were included. In final optimal scaling regression models, polymorphisms of rs4646437 (CYP3A4), age, BMI was identified to be factors of VIC min /D in Group 1 (R 2  =   .255, p < .001). Only age was confirmed as a factor of VIC min /D in Group 2 (R 2  =   0.144, p = .021). 4. Besides polymorphisms of CYP2C19, in individualized medication of voriconazole in haematological patients, polymorphisms of CYP3A4, and non-genetic factors as BMI, age should also be taken into account, especially for individuals with CYP2C19*2 or CYP2C19*3.

Neuropathic pain remains as the most frequent cause of suffering and disability around the world. The isomers paeoniflorin (PF) and albiflorin (AF) are major constituents extracted from the roots of Paeonia (P.) lactiflora Pall. Neuroprotective effect of PF has been demonstrated in animal models of neuropathologies. However, only a few studies are related to the biological activities of AF and no report has been published on analgesic properties of AF about neuropathic pain to date. The aim of this study was to compare the effects of AF and PF against CCI-induced neuropathic pain in rat and explore the underlying mechanism. We had found that both PF and AF could inhibit the activation of p38 mitogen-activated protein kinase (p38 MAPK) pathway in spinal microglia and subsequent upregulated proinflammatory cytokines (interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α)). AF further displayed remarkable effects on inhibiting the activation of astrocytes, suppressing the overelevated expression of phosphorylation of c-Jun N-terminal kinases (p-JNK) in astrocytes, and decreasing the content of chemokine CXCL1 in the spinal cord. These results suggest that both PF and AF are potential therapeutic agents for neuropathic pain, which merit further investigation.

Paeonia lactiflora root (baishao in Chinese) is a commonly used herb in traditional Chinese medicine (TCM). Paeoniflorin (PF) and albiflorin (AF) are two major active constituents of P. lactiflora. In this paper, we aimed to investigate the hematopoietic effects of PF and AF on myelosuppression mice induced by radiotherapy and to explore the underlying mechanism. The finding indicated that PF and AF significantly increased the numbers of white blood cells (WBC) and reversed the atrophy of thymus. Furthermore, PF and AF increased the levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3) and reduced the levels of tumor necrosis factor-α (TNF-α) in serum and increased the level of colony-stimulating factor (G-CSF) in plasma. Lastly, PF and AF not only enhanced the mRNA levels of GM-CSF and G-CSF in the spleens, but also increased the protein levels of G-CSF and GM-CSF in bone marrow. Our results suggest that PF and AF may promote the recovery of bone marrow hemopoietic function in a myelosuppressed mouse model.

Rural-urban differences in the prevalence of chronic diseases in the adult population of northeast China are examined. The Jilin Provincial Chronic Disease Survey used personal interviews and physical measures to research the presence of a range of chronic diseases among a large sample of rural and urban provincial residents aged 18 to 79 years (N = 21 435). Logistic regression analyses were used. After adjusting for age and gender, rural residents had higher prevalence of hypertension, chronic ischemic heart disease, cerebrovascular disease, chronic low back pain, arthritis, chronic gastroenteritis/peptic ulcer, chronic cholecystitis/gallstones, and chronic lower respiratory disease. Low education, low income, and smoking increased the risk of chronic diseases in rural areas. Reducing rural-urban differences in chronic disease presents a formidable public health challenge for China. The solution requires focusing attention on issues endemic to rural areas such as poverty, lack of chronic disease knowledge, and the inequality in access to primary care., (© 2014 APJPH.)

A simply way was proposed to prepare solid-phase microextraction (SPME) fiber with cation-exchange functional groups by the thermally initiated radical polymerization of poly(butadiene-maleic acid) (PBMA) copolymer onto a silica capillary. The capacity of the fiber coating could be easily controlled by fabricating successive layers of PBMA. The performance of the fiber combined with ion chromatography was evaluated by choosing Mg(2+) and Ca(2+) as model analytes; ∼13 and ∼51-fold enrichment factors for Mg(2+) and Ca(2+) were obtained, respectively.