Nature Communications
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2025
·Vol. 16
·期 1
·1-14
·
IF 15.7
He Wenyan,Huan Xueting,Li Yinchuan,Deng Qisen,Chen Tao,Xiao Wen,Chen Yijun,Ma Lingman,Liu Nan,Shang Zhuo,Wang Zongqiang
The rapid emergence of difficult-to-treat multidrug-resistant pathogens, combined with the scarcity of antibiotics possessing novel mechanisms, poses a significant threat to global public health. Here, we integrate the synthetic-bioinformatic natural product approach with peptide optimization to unveil the antibiotic-producing potential of Paenibacillaceae bacteria. Our culture-independent approach led to the discovery of paenimicin, a novel 11-mer depsi -lipopeptide featuring an unprecedented dual-binding mechanism. By sequestering the phosphate and hydroxyl groups of lipid A in Gram-negative bacteria, as well as the phosphate groups of teichoic acids in Gram-positive bacteria, paenimicin exhibits potent and broad-spectrum efficacy against MDR pathogens in vitro and in vivo models. Paenimicin demonstrates no detectable resistance, favorable pharmacokinetics and low nephrotoxicity, positioning it as a promising candidate for treating severe and urgent MDR infections.
研究领域:
抗菌研究
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生物信息学
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微生物学
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药理学
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传染病学
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合成生物学
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DOI
PubMed
高影响因子
Chinese Journal of Natural Medicines
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2025
·
IF 4.9
Xiaojie Fan,Yufeng Jia,Jiaxin Guo,Jinyuan Yang,Dahong Li,Huiming Hua
Ten novel xanthones, garpedunxanthones A−G ( 1 − 5 , 6a / 6b , 7a / 7b ) and nujiangxanthone Q ( 8 ), along with sixteen known analogs ( 9 − 24 ), were isolated from Garcinia pedunculata and G. nujiangensis . Their structures were elucidated through high-resolution electrospray ionization mass spectrometry (HR-ESI-MS) data, comprehensive nuclear magnetic resonance (NMR) spectroscopic analyses, and electronic circular dichroism (ECD) calculations. All compounds without cytotoxicity were assessed for anti-inflammatory properties by measuring the inhibition of nitric oxide (NO) production in lipopolysaccharide (LPS)-induced RAW264.7 cells. Structure-activity relationships are also discussed. Compounds 7b , 19 , and 21 exhibited significant anti-inflammatory activity with IC 50 values of 16.44 ± 0.69, 14.28 ± 0.78, and 10.67 ± 3.28 μmol·L −1 , respectively. Enzyme-linked immunosorbent assay (ELISA) demonstrated that compounds 7b , 19 , and 21 inhibited the expression of pro-inflammatory cytokines TNF-α and IL-6 in a dose-dependent manner. The inhibitory effect of compound 21 on IL-6 at 20 μmol·L −1 was comparable to that of the positive control. In network pharmacology studies, potential targets of compounds and inflammation were identified from PharmMapper and GeneCards databases. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that the overlapped targets were intricately associated with major pathogenic processes linked to inflammation, including positive regulation of mitogen-activated protein kinase (MAPK) cascade, protein kinase activity, NO synthase regulator activity, MAPK signaling pathway, and EGFR tyrosine kinase inhibitor resistance.
研究领域:
药理学
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植物化学
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炎症研究
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DOI
PubMed
高影响因子
Advanced Science
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2025
·
IF 14.1
Xiaodong Hu,Jiaqi Zhong,Yujiong Chen,Botao Liu,Tianyu Du,Weilai Zhu,Minzhe Zheng,Hongze Liang,Jiahua Ni,Zhaoxiang Peng
The treatment of orthopedic implant–associated infections (IAIs) presents significant challenges due to increasing drug resistance. This study reports a virulence-selective trap–capture–kill antibacterial system for effectively treating persistent infections while promoting local bone tissue regeneration by regulating disordered immune and metabolic microenvironments caused by IAIs. Here, this work fabricates a nanostructured antibacterial system (F-14-TNA) based on a TiO 2 nanotube array modified with a cationic pentacyclic coplanar backbone, fascaplysin derivative 14 (F-14). The modified surface induces a unique virulence-initiated chemotaxis behavior, with the TiO 2 nanostructure selectively trapping hyperpathogenic bacterial strains from the infecting microbiota. These trapped bacterial strains are subsequently captured by the positively charged F-14 surface via electrostatic force. The virulence-selective bacteria are then killed via a reactive oxygen species–mediated pathway regulated by the phosphotransferase system cyclic adenosine monophosphate receptor protein cascade. In vitro and in vivo studies reveal that F-14-TNA has multiple biocompatibility functions, such as effective antibacterial activity, regulation of the immune microenvironment of bone infections, and recovery of disordered bone metabolism. The nanostructure developed in this study provides a novel approach for the treatment of IAIs.
研究领域:
生物医学工程
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纳米医学
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感染免疫学
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骨科学
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微生物学
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转化医学
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材料科学
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DOI
PubMed
高影响因子
JOURNAL OF MATERIALS SCIENCE-MATERIALS IN MEDICINE
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2025
·Vol. 36
·期 1
·1-17
·
IF 4.5
Chen Shaoqing,Liang Caiqin,Li Pengyin,Liu Chun,Zeng Xierong,Xiong Xinbo,Ni Xinye
Hydroxyapatite (HA) coatings on carbon fiber-reinforced carbon (C f /C) composites hold promise for orthopedic implants. However, the interface between HA and C f /C is prone to delamination, limiting its application. To address this, a polydopamine (PDA)-polyvinyl alcohol (PVA)-graphene oxide (GO) transition layer was introduced to reinforce and toughen HA coatings on C f /C composites (PDA-PVA-GO/C f /C) via hydrothermal electro-deposition/post-hydrothermal treatment. For comparison, the PDA and PDA/PVA transition layers were also prepared on C f /C, designated as PDA/C f /C and PDA-PVA/C f /C, respectively. The precursor and transformed coatings obtained were monetite and HA. XRD analyses revealed that PDA and PVA infiltrated the monetite lattice without affecting the HA lattice parameters. Remarkably, scratch tests demonstrated that the HA/PVD-PVA-GO coating on C f /C exhibited a dense configuration and compact interfacial structure, achieving a maximum critical load of 51.5 N, surpassing other reported electrochemically prepared HA coatings. Moreover, scratch tests indicated a more homogeneous scratch pattern with no sudden delamination of the coating from the matrix. In vitro assessments revealed that all HA coatings with the transition layer exhibited enhanced bioactivity and cell compatibility compared with HA alone. In particular, PDA/PVA/GO-C f /C exhibited the best superior efficacy in promoting the proliferation of mouse embryonic osteoblast precursor (MC3T3-E1) cells and significantly increased Alkaline phosphatase (ALP) production in rat bone marrow mesenchymal stem cells (BMSCs). These findings underscore the potential of PDA-PVA-GO/C f /C as a promising biomaterial for bone regeneration. Graphical
研究领域:
生物医学工程
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材料科学
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表面工程
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生物材料
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骨科
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DOI
PubMed
高影响因子
CLINICAL ORAL IMPLANTS RESEARCH
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2025
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IF 5.3
Minghao Zuo,Heng Zhang,Jialu Lv,Yanyan Zhou,Zhijian Xie,Yiqun Zhou
Objectives This study aimed to develop a novel self-glazed zirconia (SZr) dental implant featuring micro/nano-roughened thread and polished neck, and to examine its properties both in vitro and in vivo. Material and Methods The micro/nano-roughened SZr surfaces (SZr-MN) were manufactured using sandblasting and chemical vapor deposition. Surface topography, elemental composition, roughness, and contact angle were systematically characterized. Streptococcus mutans and Porphyromonas gingivalis were used to evaluate bacterial adhesion. Bone marrow mesenchymal stem cells (BMSCs) and human immortalized keratinocytes were used to assess cell adhesion, proliferation, and osteogenic differentiation. The sandblasting large-grit acid-etching treated titanium (Ti) surfaces (Ti-SLA) served as the control. Ti and SZr implants were inserted into the mandibles of Beagle dogs, followed by radiological, fluorescent, and histomorphometric analyses after 8 and 12 weeks of healing. Results The SZr-MN surface exhibited micro-scale ravines and gullies densely covered with curled, sheet-like nano-structures, which led to suitable roughness and improved hydrophilicity. Compared to the Ti-SLA surface, the SZr-MN surface demonstrated significantly reduced bacterial adhesion, along with increased adhesion and osteogenic differentiation of BMSCs. Consequently, the SZr implant achieved more extensive and denser surrounding bone tissue and enhanced osseointegration compared to the Ti implant, while both showed comparable dimensions of peri-implant soft and hard tissues. Conclusions The novel SZr implant surfaces demonstrated excellent antibacterial activity, biocompatibility, and proosteogenic effect, leading to enhanced osseointegration and satisfactory soft tissue sealing. Our findings offer a unique perspective on improving the biological activity of zirconia dental implants.
研究领域:
牙科
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生物材料
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生物医学工程
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微生物学
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细胞生物学
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DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2025
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IF 5.6
Fei Wang,Chao Jiang,Teng-Jie Wang,Xin Pan,Bin Che,Ding-Yi Zhang,Kai-Long Zhang,Ping Zhou,Ke-Feng Ren
Bacterial infections, aseptic loosening, and poor osseointegration remain challenges for orthopedic implants. In this study, we developed a dual-network polyelectrolyte antibacterial coating for orthopedic implants to prevent bacterial infections. The coating was prepared via UV-triggered in situ polymerization, composed of polyethyleneimine (PEI) and polyacrylic acid (PAA), with enhanced mechanical properties due to electrostatic interactions between them. The antimicrobial peptide ε-poly-L-lysine (EPL) was immobilized in the coating, providing efficient antibacterial functionality. The coating's substrate was made of hydroxyapatite (HA) and polylactic acid (PLA) composites to promote bone cell growth and tissue regeneration. In vitro experimental results demonstrated that the coating exhibited excellent antibacterial properties against both Gram-negative and Gram-positive bacteria, while enhancing the adhesion, proliferation, and differentiation of osteoblasts. In vivo experiments further confirmed the coating's capability to resist infection in an infected microenvironment. This study provides a practical strategy for developing orthopedic implant surface coatings with antibacterial functions.
研究领域:
生物医学工程
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材料科学
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骨科
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抗菌技术
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组织工程
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DOI
PubMed
高影响因子
BLOOD
·
2025
·Vol. 145
·期 10
·1074-1088
·
IF 23.1
Yong Long,Qianqian Zhang,Ling Ling,Yuan Zhuang,Xiaolei Wei,Haoyang Huang,Zhanping Lu,Yushan Huang,Xianming Chen,Yuhua Ye,Xiaoqin Feng,Haokun Zhang,Binbin Huang,Yueyan Huang,Yidan Liang,Mingyan Fang,Yukio Nakamura,Bin Lin,Xinhua Zhang,Daru Lu,Xin Jin,Xiangmin Xu
Accumulation of free α-globin is a critical factor in the pathogenesis of β-thalassemia. Autophagy plays a crucial role in clearing toxic free α-globin, thereby reducing disease severity. However, the impact of natural mutations in autophagy-related genes (ATGs) on the phenotypic variability of β-thalassemia remains unclear. In this study, we systematically investigated the relationship between variants in ATGs and disease phenotypes in a cohort of 1022 patients with β-thalassemia, identifying 4 missense mutations in the autophagy and beclin 1 regulator 1 (AMBRA1) gene. Disruption of the Ambra1 gene in β-thalassemic mice was found to reduce autophagic clearance of α-globin in red blood cell precursors, exacerbating disease phenotypes. Functional characterization of the AMBRA1 gene and these mutations in patient-derived CD34+ cells, edited human umbilical cord blood–derived erythroid progenitor 2 (HUDEP-2) cells, and engineered HUDEP-2 β-thalassemic cells confirmed that AMBRA1 facilitates the autophagic clearance of free α-globin in human erythroid cells. Functional studies demonstrated that AMBRA1 missense mutants destabilize Unc-51-like kinase 1 protein, inhibit light chain 3 protein lipidation, and subsequently hinder autophagic flux, leading to increased α-globin deposition. Additionally, these mutations were associated with erythrotoxic effects in vitro, including increased intracellular reactive oxygen species levels, higher apoptosis rates, and impaired erythroid differentiation and maturation. This study sheds light on the molecular association between mutations in ATGs and the exacerbation of β-thalassemia, highlighting the potential role of the AMBRA1 gene as a promising diagnostic and therapeutic target for β-hemoglobinopathies.
研究领域:
血液学
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分子生物学
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遗传学
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DOI
PubMed
高影响因子
ADVANCED MATERIALS
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2025
·
IF 26.8
Xiaoya Ding,Jiante Li,Luoran Shang,Yuanjin Zhao
The use of micromotors-based delivery systems for inflammatory bowel disease (IBD) treatment has recently gained considerable interest. The current research primarily focuses on how to design micromotors with more elaborate geometries and actuation mechanisms to improve IBD therapeutic effects. Herein, a novel type of reactive oxygen species (ROS)-responsive hemispheroid adhesive micromotors (HMPs) as efficient delivery systems is developed to treat IBD. Such HMPs are fabricated through microfluidic electrospray technique, with a platinum (Pt) layer and dopamine (DOPA) coating layer covered on its top surface and baseplate, respectively. The Pt on HMPs′ top surface can produce oxygen from hydrogen peroxide, thereby providing a propulsion force for them to move spontaneously upon exposure to ROS environment. Moreover, the DOPA layer on the baseplate contributed to the outstanding adhesive capacity to tissues. Therefore, by incorporating anti-inflammatory dexamethasone (DXM) into HMPs, the resultant micromotor systems are imparted with superior antioxidant and anti-inflammatory capacities, which also exhibits desirable therapeutic effect upon treating IBD by alleviating inflammatory response, restoring epithelial barrier functions, and mitigating IBD-associated symptoms. The treatment mechanism of DXM-loaded HMPs mainly involves alleviating oxidative stress, reducing proinflammatory cytokines secretion, and protecting intestinal barrier. Collectively, these results illustrate HMPs-based micromotor systems are valuable for gastrointestinal disease treatment.
研究领域:
生物医学工程
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药物递送系统
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纳米医学
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胃肠病学
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微型机器人
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产品关联
DOI
PubMed
高影响因子
LIFE SCIENCES
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2018
·
IF 3.234
Shuli Fan,Xiang Gao,Peng Chen,Xu Li
Myricetin has been reported to promote osteogenic differentiation and inhibit osteoclastogenesis. The aim of this study was to investigate the potential effects of myricetin on glucocorticoid-induced osteoporosis (GIOP) both in vivo and in vitro . Male Sprague-Dawley (SD) rats were given dexamethasone (DEX, 0.1 mg/kg, s.c.) once daily and myricetin (1 mg/kg or 2.5 mg/kg, i.p.) once every other day for a total of five weeks. Body weight was recorded once a week. Bone mineral density (BMD), the activities or levels of bone turnover markers, and histological changes were assessed. MC3T3-E1 cells were incubated with DEX (1 μM) and myricetin (20 μM). Osteoblast proliferation, differentiation and mineralization were evaluated. U0126 was added to evaluate the involvement of the ERK signaling pathway. The results showed that myricetin increased body weight gain and inhibited DEX-induced reduction in BMD, enhanced alkaline phosphatase (ALP) activity, and upregulated osteocalcin (OCN), bone morphogenetic protein 2 (BMP2) and runt-related transcription factor 2 (Runx2) levels, whereas reduced tartrate-resistant acid phosphatase (TRAP) activity and C-terminal telopeptide of type I collagen (CTx) level. In addition, myricetin ameliorated histological changes in the femurs. In our in vitro studies, myricetin promoted osteoblast differentiation and mineralization in DEX-treated MC3T3-E1 cells, accompanied by increases in BMP2, Runx2, ALP, OCN, collagen type I alpha 1 (COL1A1) and osteopontin (OPN) levels. The promotion effects of myricetin on osteogenic differentiation and matrix mineralization were reversed by U0126. These results suggest that myricetin may alleviate DEX-induced osteoporosis by promoting osteogenic differentiation and matrix mineralization via the ERK signaling pathway.
研究领域:
药理学
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骨科
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细胞生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2025
·
IF 5.4
Wēi Wang,Jian Zhang,Song-Lin Jiang,Zhi-Min Rao,Hui Liu,Lei Wang,Chun-Li Cai,Xin-Chang Xu,Chen-Huan Yu,Wéi Wang
Ethnopharmacological relevance Psoriasis is an immune-mediated genetic skin disease, which is characterized by hyperproliferation and aberrant differentiation of epidermal keratinocytes. Recently, there are not any cures for psoriasis because of the limited availability of safe and effective medications. Dictamni Cortex is the root bark of Dictamnus dasycarpus Turcz. And exhibits anti-inflammatory, antibacterial, hepatoprotective and anticancer activities. It is widely used for preventing various bone and skin diseases, including rheumatoid arthritis, psoriasis, eczema and impetigo. However, the active compounds responsible for treating psoriasis in the herb remain unknown. Aim of the study To investigate the inhibitory effects of active compounds in the herb against the hyperproliferation of human HaCaT keratinocytes in vitro and imiquimod (IMQ)-induced psoriasis-like dermatitis in mice. Materials and methods The effects of each active compound in the herb against the proliferation, apoptosis, migration, and invasion of HaCaT cells were analyzed by MTT, flow cytometry, and Transwell assays, respectively. The profiles of differentially expressed mRNAs between model group and dictamnine (DIC)-treated group were compared by transcriptome sequencing. The levels of inflammatory cytokines and chemokines in the mediums and skin tissues were measured by ELISA assay. IMQ-induced psoriasis-like dermatitis in mice were evaluated by HE stain and immunohistochemical analysis. The expressions of HIF1A and its downstream were measured by western blotting analysis. Results Compared with the methanol extract and other active compounds, DIC displayed the strongest inhibition on the hyperproliferation of KGF-stimulated HaCaT cells. DIC remarkably inhibited the proliferation, migration and invasion of HaCaT cells in a concentration-dependent manner. It also reduced the production of IL-6, IL-23 and VEGF, the activities of GSH and SOD, and the expressions of K17 , CCL20 and CXCL2 mRNAs, but elevated the levels of ROS, Fe 2+ and MDA in KGF-exposed HaCaT cells. Moreover, DIC significantly mitigated imiquimod-induced psoriasis-like dermatitis in mice. Mechanically, DIC promoted the ferroptosis of HaCaT cells via targeting HIF1A, thereby suppressing the nuclear translocation of HIF1A and its dowmstream GPX4 and SLC7A11. These benefits of DIC treatment could be reversed by ferroptotic inhibitor Ferrostatin-1 and HIF1A stabilizer DMOG. Conclusions DIC ameliorated psoriasis in part by triggering HIF1A-dependent ferroptosis in keratinocytes. It suggested that DIC was the main active compound in D. Cortex and has therapeutic potential for the treatment of psoriasis.
研究领域:
药理学
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皮肤科
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分子生物学
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民族药理学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2024
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IF 6.7
Kaineng Huang,Yi He,Xingyu Li,Yuanjiang Pan,Yuanji Gao
Herein, a new strategy is employed to build a controllable thermal-coupled charge ionization (TCCI) device to elucidate the desorption–ionization mechanism of plasma ion sources. Efficient synergistic desorption and ionization are achieved within the TCCI device by independently controlling the desorption temperature and plasma charges. The TCCI device efficiently ionizes samples using abundant free electrons, charges, and active species from arc plasma. The coexistence of free electrons and hydroxide radicals confers redox capability to the TCCI system, implying the presence of a unified redox mechanism even when the arc plasma is transmitted through a metal conductor over a distance. In addition, molecular ions of the analytes facilitate the differentiation between primary and secondary amines during their analysis. Notably, the TCCI device enables a switch between hard and soft ionization by adjusting the thermal desorption temperature. At high temperatures (>400 °C), the TCCI device exhibits hard ionization characteristics, producing fragment ions beneficial for isomer discrimination. The TCCI mass spectrometry exhibits robust performance in terms of sensitivity and accuracy for detecting antibiotics and sterols in saline solutions, achieving linearity with correlation coefficients ≥0.99 and excellent reproducibility. The successful analysis of seven pharmaceuticals and four sterols in complex matrices using the TCCI device demonstrates its excellent salt and matrix tolerance. Overall, the TCCI device, with its independent control over thermal desorption and arc plasma, achieves efficient synergistic desorption and ionization, overcoming limitations in existing ionization technologies and contributing to the study of gas-phase ion dynamics and mechanisms.
研究领域:
分析化学
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质谱学
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等离子体科学
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产品关联
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2025
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IF 6.1
Yue Zhang,Hui Zhao,Qianxi Feng,Rui Guo,Li Zhong,Shengxian Liang
Benzotriazole ultraviolet stabilizers (BUVSs) are pervasive environmental contaminants that pose significant risks to human health. This study evaluated the effects of three typical BUVSs (UV-328, UV-329, and UV-P) on human mesenchymal stem cells (hMSCs), which play crucial roles in tissue maintenance and repair. hMSCs were exposed to BUVSs across a range of concentrations, and their maintenance and differentiation capacities were assessed. At concentrations below 50 μM, no significant cytotoxicity was observed. However, at non-cytotoxic doses, UV-P exhibited stronger effects on the differentiation of hMSCs compared to UV-328 and UV-329, significantly inhibiting adipogenesis and enhancing osteogenesis. Mechanistically, UV-P was found to significantly enrich the PPAR signaling pathway during both differentiation processes. Dual-luciferase reporter assays confirmed UV-P's interaction with PPARγ_LBD at an alternate binding site outside the canonical pocket. These findings raise concerns about the health impacts of BUVSs, particularly UV-P, and underscore the need for further investigation into their toxicological profiles.
研究领域:
细胞生物学
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毒理学
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环境健康科学
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DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）