CHEMICAL ENGINEERING SCIENCE
·
2024
·
IF 4.1
Zhongjian Tan,Yuwei Yan,Jiacong Liao,Huanhuan Shi,Yun Zheng,Weizheng Xu,Chen Yi,Zhiying Dai,Chenyang Xu
Droplet microfluidic technology can use each microdroplet as a microreactor, which has the advantages of low reagent dosage, less cross contamination, and fast reaction time. Combining concentration gradient generation with droplet formation and capture to form a two-dimensional reaction condition screening platform (including reactant concentration and reaction time) is expected to broaden the application range of microfluidic screening. In this work, a microfluidic chip that can dynamically generate and capture microdroplets and form static microdroplet array was designed and fabricated. An optimized Christmas tree structure by adjusting the horizontal channel length ratio was used to generate a chemical concentration gradient while obtaining a uniform outlet flow rate, forming a droplet array with different concentrations. The performance of droplet array with microfluidic concentration gradient (DA-MCG) was verified using sodium fluorescein as a model reagent. The chromogenic reaction of NaOH and phenolphthalein, and luminol chemiluminescence reaction were used to verify the two-dimensional screening ability of DA-MCG. The results indicated that the DA-MCG has the potential to be applied in the field of multi-dimensional drug screening.
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JOURNAL OF MEDICINAL CHEMISTRY
·
2025
·
IF 6.8
Lei Xu,Yaling Wang,Sangyu Hu,Yuzhu Pei,Chenliang Qian,Wenjie Xue,Gao Zhang,Song Wu,Xinxin Si,Xuming Deng,Jie Xia,Jianfeng Wang
To date, the abuse of antibiotics and a gradual decline in novel antibiotic discovery enlarge the threat of drug-resistant bacterial infections, especially methicillin-resistant Staphylococcus aureus (MRSA). Herein, inspired by the unique structures and antibacterial activities of 2-quinolones, a class of novel 2-quinolones with substituted pyridines was synthesized. Notably, compound 11, the derivative with a methylpyridine fragment, showed potent antibacterial and antibiofilm activities, especially for MRSA strains (MIC = 0.02–0.04 μg/mL). A mechanistic study of compound 11 revealed that the increase of intracellular ROS and acceleration of the TCA cycle, which reprogrammed the bacterial metabolism, eventually triggered membrane damage and bacterial death. Most importantly, compound 11, with antibacterial and anti-inflammatory properties, accelerated the reconstruction and healing of MRSA-infected cutaneous wounds by decreasing bacterial loads, attenuating inflammation, and promoting angiogenesis. Overall, these findings provide a novel multifunctional chemotype with broad-spectrum antibacterial activity and highlight a promising strategy for MRSA-infected wound healing.
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ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2024
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IF 6.2
Yihan Hu,Yiming Sun,Haolin Zhang,Linghuan Luo,Haibin Wang,Ruili Zhang,Ming Ge
2-ethylhexyl diphenyl phosphate (EHDPHP) is a widely used organophosphorus flame retardant and plasticizer, which is commonly found in the environment. EHDPHP not only potentially harms the environment but also causes different degrees of damage to the organism. In this study, the duodenum of chicks was selected as the potential toxic target organ to explore the mechanism of duodenal injury induced by EHDPHP exposure. Ninety one-day-old healthy male chicks were selected and randomly divided into C1(control group), C2(solvent control group), L(800 mg/kg), M(1600 mg/kg), H(3200 mg/kg) according to different doses of EHDPHP after one week of environmental adaptation. The chicks were given continuous gavage for 14 d, 28 d, and 42 d. It was found that constant exposure to EHDPHP caused an increase in duodenal MDA content, a decrease in P-gp, SOD, GSH-Px activities, and a decrease in duodenal mucosal immune factor (sIgA, GSH-Px). The expression of sIgM and mucosal link proteins (CLDN, OCLN, ZO-1, JAM) decreased, and the expression of the inflammatory protein (NF-κB, COX2) in duodenal tissues was up-regulated. The results showed that continuous exposure to EHDPHP could cause duodenal oxidative stress, inflammation, and mucosal barrier damage in chicks, which provided a basis for studying the mechanism of toxic damage caused by EHDPHP in poultry.
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JOURNAL OF CONTROLLED RELEASE
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2024
·
IF 10.5
Yu Sun,Xiuhua Zhang,Wanrong Hong,Yingfeng Qin,Yunan Man,Maolin He,Jin-Wen Liu,Jia Chen
Growth factor holds great promise for bone regeneration, and spatiotemporal control of their expressing through site-specific reactions is crucial but challenging for on-demand therapy. In this study, we present the development of a novel unnatural amino acids (UAAs)-triggered therapeutic switch (UATS) system, composed of an orthogonal aminoacyl-tRNA-synthase (aaRS)-tRNA pair and a bone morphogenetic protein 2 (BMP2) gene harboring premature stop codon, which enable in situ and on-demand initiation of the expression of BMP2. The resulting UATS system allowed specifically control of base expressing on the BMP2 mRNA that switched to the BMP2 protein with complete structure and function to facilitate bone regeneration. Our investigations showed that the UATS system exhibits remarkable attributes of rapid, sensitive, reversible, and sustained BMP2 expression both in vitro and in vivo settings. Moreover, the implantation of microencapsulated cells with UATS system is applied to a mouse femur defect model, demonstrating high effciency in controlled expressing of BMP2 protein and substantial repair of bone defect following oral administration of UAAs. Therefore, our findings underscore the great potential of UATS system for on-demand awakening of functional growth factor, thus offering promising prospects in the realm of regenerative medicine.
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MOLECULAR CELL
·
2024
·
IF 14.5
Zhenxi Zhang,Yanting Yang,Yang Chen,Jingyu Su,Wenjing Du
The functional integrity of CD8 + T cells is closely linked to metabolic reprogramming; therefore, understanding the metabolic basis of CD8 + T cell activation and antitumor immunity could provide insights into tumor immunotherapy. Here, we report that ME2 is critical for mouse CD8 + T cell activation and immune response against malignancy. ME2 deficiency suppresses CD8 + T cell activation and anti-tumor immune response in vitro and in vivo . Mechanistically, ME2 depletion blocks the TCA cycle flux, leading to the accumulation of fumarate. Fumarate directly binds to DAPK1 and inhibits its activity by competing with ATP for binding. Notably, pharmacological inhibition of DAPK1 abolishes the anti-tumor function conferred by ME2 to CD8 + T cells. Collectively, these findings demonstrate a role for ME2 in the regulation of CD8 + T cell metabolism and effector functions as well as an unexpected function for fumarate as a metabolic signal in the inhibition of DAPK1.
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Polymers
·
2024
·Vol. 16
·期 13
·1863
·
IF 4.7
Yan Qiu,Xinyang Zhao,Hong Li,Sijun Liu,Wei Yu
The viscosity and viscoelasticity of polyelectrolyte solutions with a single electrostatic interaction have been carefully studied experimentally and theoretically. Despite some theoretical models describe experimental results well, the influence of multiple interactions (electrostatic and hydrophobic) on rheological scaling is not yet fully resolved. Herein, we systematically study the microstructures and rheological properties of short-side-chain perfluorosulfonic acid (S-PFSA), the most promising candidate of a proton exchange membrane composed of a hydrophobic backbone with hydrophilic side-chains, in water/2-propanol. Small-angle X-ray scattering confirms that semiflexible S-PFSA colloidal particles with a length of ~38 nm and a diameter of 1–1.3 nm are formed, and the concentration dependence of the correlation length (ξ) obeys the power law ξ~c−0.5consistent with the prediction of Dobrynin et al. By combining macrorheology with diffusing wave spectroscopy microrheology, the semidilute unentangled, semidilute entangled, and concentrated regimes corresponding to the scaling relationships ηsp~c0.5, ηsp~c1.5, and ηsp~c4.1are determined. The linear viscoelasticity indicates that the entanglement concentration (ce) obtained from the dependence of ηspon the polymer concentration is underestimated owing to hydrophobic interaction. The true entanglement concentration (cte) is obtained by extrapolating the plateau modulus (Ge) to the terminal modulus (Gt). Furthermore, Geand the plateau width, τr/τe(τrand τedenote reptation time and Rouse time), scale as Ge~c2.4and τr/τe~c4.2, suggesting that S-PFSA dispersions behave like neutral polymer solutions in the concentrated regime. This work provides mechanistic insight into the rheological behavior of an S-PFSA dispersion, enabling quantitative control over the flow properties in the process of solution coating.
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Materials Today Communications
·
2025
·
IF 4.5
Shuhong Nie,Zheng Wang,Xiaohui Jiang,Liangmin Yu,Mengxuan Sun
Reasonable heteroatom doping and structural construction can improve the performance of electromagnetic wave (EMW) absorbing materials. Eugenol-acrylate monomer (EAM) with rich double bonds is synthesized from eugenol and acrylic anhydride by esterification without solvation. EAM and acrylonitrile (AN) are used as raw materials, the EAM as a source of carbon, the AN as nitrogen source. According to different molar ratios, a series of eugenol-group polymer microspheres with particle size ranging from 0.8 to 1.5μm are prepared by precipitation polymerization through one-pot method. Furthermore, N-doped carbonization microspheres with excellent EMW absorption properties are prepared by a controlled carbonization process with particle size ranging from 0.4 to 1.0μm. In this study, the molar ratios of EAM and AN are adjusted to optimize the EMW absorption properties of the prepared EMW absorbing materials of carbonization microspheres. It is confirmed that carbonization microspheres have good EMW absorption performance at an EAM to AN ratio of 7:3 and a thickness of 3 mm, the minimum reflection loss (RL min ) is −40.89 dB (12.56 GHz), and the effective absorption bandwidth (EAB) is 5.01 GHz (10.01–15.02 GHz). In this work, derivatives of eugenol with rich double-bond from a wide range of sources are involved in the process of copolymerizing microspheres maintained morphological stability before and after carbonization, which provided an efficient and easy method for the preparation of nitrogen and oxygen doped carbon microspheres, enriched the types of wave absorbing materials, and laid a foundation for future work.
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TALANTA
·
2024
·
IF 5.6
Xiaohu Liu,Ruifeng Xie,Kang Li,Zhelei Zhu,Xi Huang,Qian He,Zhe Sun,Haiyang He,Yuancai Ge,Qingwen Zhang,Hu Chen,Yi Wang
We have developed a convenient surface-enhanced Raman scattering (SERS) platform based on vertical standing gold nanowires (v-AuNWs) which enabled the on-mask detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) related substances such as the Spike-1 protein and the corresponding pseudo-virus. The Spike-1 protein was clearly distinguished from BSA protein with an accuracy above 99 %, and the detection limit could be achieved down to 0.01 μg/mL. Notably, a similar accuracy was achieved for the pseudo-SARS-CoV-2 (pSARS-2) virus as compared to the pseudo-influenza H7N9 (pH7N9) virus. The sensing strategy and setups could be easily adapted to the real SARS-CoV-2 virus and other highly contagious viruses. It provided a promising way to screen the virus carriers by a fast evaluation of their wearing v-AuNWs integrated face-mask which was mandatory during the pandemic.
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CRYSTENGCOMM
·
2024
·Vol. 27
·期 1
·38-45
·
IF 2.6
Jiali Han,Shujun Zhu,Xinxin Chen,Haichao Zhou,Jianguo Pan,Shangke Pan
In recent years, lead-free organic–inorganic hybrid zero-dimensional metal halides have attracted considerable attention due to their outstanding optical properties, largely attributed to the confinement of localized metal groups. We report the discovery of a newly structured [MMim]2[CuI3] crystal with a distinct [CuI3]2− trigonal planar structure encapsulated by inert organic [MMim]+ clusters. The structure, composition, and thermal stability of the crystal were analyzed using XRD and TG–DTA. The optical properties of [MMim]2[CuI3] crystals were both experimentally measured and theoretically calculated. These crystals exhibit intense broadband orange luminescence with pronounced Stokes shifts and a microsecond-scale fluorescence lifetime decay, primarily due to self-trapped exciton emission. Temperature-dependent fluorescence spectra were also recorded to explore the luminescence mechanism. In summary, these findings highlight the remarkable potential of lead-free [MMim]2[CuI3] crystals in advancing optoelectronic applications.
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BMC MUSCULOSKELETAL DISORDERS
·
2024
·
IF 2.2
Kuishuai Xu,Liang Zhang,Tianrui Wang,Tengbo Yu,Xia Zhao,Yingze Zhang
Objective Type 2 diabetes mellitus (T2DM) is one of the high risk factors for sarcopenia. However, the pathogenesis of diabetic sarcopenia has not been fully elucidated. This study obtained transcriptome profiles of gastrocnemius muscle in normal and T2DM rats based on high-throughput sequencing technology, which may provide new ideas for exploring the pathogenesis of diabetic sarcopenia. Methods Twelve adult male Sprague-Dawley rats were randomly divided into Control group and T2DM group, and gastrocnemius muscle tissue was retained for transcriptome sequencing and real-time quantitative polymerase chain reaction (qRT-PCR) 6 months later. Screening differentially expressed genes (DEGs), Cluster analysis, gene ontology (GO) functional annotation analysis and Kyoto Encyclopedia of Genes and Gnomes (KEGG) functional annotation and enrichment analysis were performed for DEGs. Six DEGs related to apoptosis were selected for qTR-PCR verification. Results Transcriptomic analysis showed that there were 1016 DEGs between the gastrocnemius muscle of T2DM and normal rats, among which 665 DEGs were up-regulated and 351 DEGs were down-regulated. GO analysis showed that the extracellular matrix organization was the most enriched in biological processes, with 26 DEGs. The extracellular matrix with 35 DEGs was the most abundant cellular component. The extracellular matrix structural constituent, with 26 DEGs, was the most enriched in molecular functions. The highest number of DEGs enriched in biological processes, cellular components and molecular functions were positive regulation of transcription by RNA polymerase II, nucleus and metal ion binding, respectively. There were 78, 230 and 89 DEGs respectively. KEGG pathway enrichment analysis showed that ECM-receptor interaction, PI3K-Akt signaling pathway and TGF-β signaling pathway( p < 0.001) had higher enrichment degree and number of DEGs. qRT-PCR results showed that the fold change of Map3k14, Atf4, Pik3r1, Il3ra, Gadd45b and Bid were 1.95, 3.25, 2.97, 2.38, 0.43 and 3.6, respectively. The fold change of transcriptome sequencing were 3.45, 2.21, 2.59, 5.39, 0.49 and 2.78, respectively. The transcriptional trends obtained by qRT-PCR were consistent with those obtained by transcriptome sequencing. Conclusions Transcriptomic analysis was used to obtain the “gene profiles” of gastrocnemius muscle of T2DM and normal rats. qRT-PCR verification showed that the genes related to apoptosis were differentially expressed. These DEGs and enrichment pathways may provide new ideas for exploring the pathogenesis of diabetic sarcopenia. Supplementary Information The online version contains supplementary material available at 10.1186/s12891-024-07568-x.
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SENSORS AND ACTUATORS B-CHEMICAL
·
2025
·
IF 7.7
Yue-Yang Zhang,Le-Yu Huang,Huiling Wang,Sixuan Meng,Fei Yang,Shi-Yu Liu
Carboxylesterase 2 (CES2), an extensively expressed serine esterase which widely distributed in various organs and tissues, exerts important roles in maintaining normal physiological function while abnormal expression of CES2 was correlated with many metabolic diseases and cancers. Thus, to develop efficient tool for detection of CES2 activity is of great importance in related clinical diagnosis and research of physiological function of CES2. To date, several enzyme-activated fluorescent probes were developed for CES2 sensing. Among which regulation of CES2 in diseases such as diabetics, colitis, cancers and liver injury could be visualized. However, even though CES2 displayed relatively high expression level in kidney, its regulation in pathological process of kidney injury was rarely studied, and thus related preliminary investigation is in urgent demand. Herein, by rational design and construction of an enzyme-activated fluorescent probe (named as DDXB ) with high catalytic efficacy, sensitivity and specificity toward CES2, down-regulation of CES2 activity in acetaminophen (APAP)-induced liver injury and dextran sulfate sodium (DSS)-induced colitis model was successfully visualized. Most importantly, aberrant up-regulation of CES2 in streptozotocin (STZ), renal ischemia reperfusion (IR) injury (RIRI) and cisplatin (CDDP)-induced kidney injury model was first revealed via DDXB- based fluorescence imaging and further confirmed by immunohistochemistry (IHC) staining. Thus, preliminary evidence for identifying CES2 as potential biomarker of kidney injury were first provided, and the newly developed probe could serve as an efficient tool for related diagnosis or further investigation of CES2 physiological function in more diseases.
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JOURNAL OF FLUORESCENCE
·
2024
·
IF 2.6
Dai Zhengyuan,Liu Hao,Sun Xuyuan,Wang Ying,Fan Jie,Li Li,Ding Yaping
Using o-phenylenediamine as carbon source and phytic acid as phosphorus source, two P-rich carbon quantum dots RCDs and BCDs were synthesized successfully by changing the reaction temperature and time of hydrothermal method. It was found that RCDs with red emission could realize sensitive detection of 2-methylimidazole, and 2-methylimidazole had no obvious quenching effect on BCDs with blue emission, which made RCDs a sensitive, quick and selective fluorescence sensor for 2-methylimidazole detection. Under the optimal experimental conditions, the fluorescence intensity of RCDs decreased with the increasing of 2-methylimidazole concentration. The detection of 2-methylimidazole concentration by the carbon quantum dots sensor showed a good linear relationship in the range of 5 ~ 110 µM, and the low detection limit was 0.61 µM (S/N = 3). The sensor is able to detect 2-methylimidazole in lake water, enabling the application of real samples. The results show that this work provides a simple fluorescence method to detect 2-methylimidazole in water.
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