CHEMBIOCHEM
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2023
·
IF 3.2
Xin Li,Changzheng Gao,Wanqing Wei,Wei Song,Weiwei Meng,Jia Liu,Xiulai Chen,Cong Gao,Liang Guo,Liming Liu,Jing Wu
Graphical We developed a pathway for the synthesis of L-ABA in a tri-enzymatic cascade in Escherichia coli BL21 (DE3) using L-Thr, and the expression of three enzymes was optimized by vector design. We solved the crystal structure of the key enzyme LDH and proposed protein engineering strategies based on the structure to improve the catalytic activity of the enzyme. L-2-aminobutyrate (L-ABA) is an important chiral drug intermediate with a key role in modern medicinal chemistry. Here, we describe the development of an efficient method for the asymmetric synthesis of L-ABA in a tri-enzymatic cascade in Escherichia coli BL21 (DE3) using a cost-effective L-Thr. Low activity of leucine dehydrogenase from Bacillus thuringiensis ( Bt LDH) and unbalanced expression of enzymes in the cascade were major challenges. Mechanism-based protein engineering generated the optimal triple variant Bt LDH M3 (A262S/V296C/P150M) with 20.7-fold increased specific activity and 9.6-fold increased k cat / K m compared with the wild type. Optimizing plasmids with different copy numbers regulated enzymatic expression, thereby increasing the activity ratio (0.3 : 1:0.6) of these enzymes in vivo close to the optimal ratio (0.4 : 1 : 1) in vitro . Importing the optimal triple mutant Bt LDH M3 into our constructed pathway in vivo and optimization of transformation conditions achieved one-pot conversion of L-Thr to 130.2 g/L L-ABA, with 95 % conversion, 99 % e.e . and 10.9 g L −1 h −1 productivity (the highest to date) in 12 h on a 500 mL scale. These results describe a potential biosynthesis approach for the industrial production of L-ABA.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2018
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IF 3.909
Qiang Chu,Meng Chen,Dongxiao Song,Xixi Li,Yunyun Yang,Zihuan Zheng,Yonglu Li,Yangyang Liu,Lushuang Yu,Zheng Hua,Xiaodong Zheng
Oxidative stress is a critical cause for the progression of neurodegenerative diseases, indicating that screening natural antioxidant and pharmacological targeting of mechanism need more attention. Natural plant polysaccharides are the primary group of natural antioxidants showing mighty antioxidant activity. Therefore, a polysaccharide (AFP-2) from flowers of Apios americana Medik was isolated, purified and characterized. Then, a H 2 O 2 -induced PC12 cells oxidative stress model was established to investigate the neuroprotective role of AFP-2 and to clarify the potential mechanism of action against H 2 O 2 -induced neurotoxicity. It was found that AFP-2 reduced ROS production and mitochondrial damage caused by hydrogen peroxide in PC12 cells. In addition, data from transmission electron microscope and western blot displayed that AFP-2 significantly activated autophagy in PC12 cells via Akt-mTOR pathway. These results together qualify AFP-2 as an interesting natural polysaccharide worth further investigation as a neuroprotective agent.
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NEW JOURNAL OF CHEMISTRY
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2020
·Vol. 44
·期 37
·15908-15918
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IF 3.288
Xiuna Yu,Zhixiang Liu,Yemei Wang,Hongyu Luo,Xu Tang
Insights into active sites and charge transport behavior are challenging topics for fabricating composite photocatalysts and investigating their photocatalytic degradation reaction mechanisms. Herein, novel composites comprising biomass charcoal and graphitic carbon nitride (CN) were fabricated via facial alkali catalysis and thermal condensation of corncob and melamine precursors. By fine-tuning the calcination temperature, the carbonization temperature of corncob-derived biomass charcoal was controlled, which had a great influence on the optimal photocatalytic activity of C–CN-600, which was 90% of the degradation activity of 2-mercaptobenzothiazole (MBT), and about 2-fold higher than that of pure CN. The corncob not only acts as a precursor for biomass charcoal, but can also prevent the agglomeration of CN at high temperature. Moreover, the charge carrier lifetime, visible light absorption and surface area are also revealed in detail by systematic characterization. In addition, the intermediate products of MBT, the degradation reaction pathway, and the mechanism over C–CN are revealed in depth.
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Nature Communications
·
2024
·Vol. 15
·期 1
·1-23
·
IF 14.7
Luo Yu-Wei,Zhou Jiang-Peng,Ji Hongyu,Xu Doudou,Zheng Anqi,Wang Xin,Dai Zhizheng,Luo Zhicheng,Cao Fang,Wang Xing-Yue,Bai Yunfang,Chen Di,Chen Yueming,Wang Qi,Yang Yaying,Zhang Xinghai,Chiu Sandra,Peng Xiaozhong,Huang Ai-Long,Tang Kai-Fu
Though RNAi and RNA-splicing machineries are involved in regulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication, their precise roles in coronavirus disease 2019 (COVID-19) pathogenesis remain unclear. Herein, we show that decreased RNAi component (Dicer and XPO5) and splicing factor (SRSF3 and hnRNPA3) expression correlate with increased COVID-19 severity. SARS-CoV-2 N protein induces the autophagic degradation of Dicer, XPO5, SRSF3, and hnRNPA3, inhibiting miRNA biogenesis and RNA splicing and triggering DNA damage, proteotoxic stress, and pneumonia. Dicer, XPO5, SRSF3, and hnRNPA3 knockdown increases, while their overexpression decreases, N protein-induced pneumonia’s severity. Older mice show lower expression of Dicer, XPO5, SRSF3, and hnRNPA3 in their lung tissues and exhibit more severe N protein-induced pneumonia than younger mice. PJ34, a poly(ADP-ribose) polymerase inhibitor, or anastrozole, an aromatase inhibitor, ameliorates N protein- or SARS-CoV-2-induced pneumonia by restoring Dicer, XPO5, SRSF3, and hnRNPA3 expression. These findings will aid in developing improved treatments for SARS-CoV-2-associated pneumonia.
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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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JOURNAL OF ALLOYS AND COMPOUNDS
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2025
·
IF 6.3
Chunyan Fan,Xuxin Song,Yao Tang,Zehao Zang,Yangyang Ren,Lanlan Li,Xiaofei Yu,Xiaojing Yang,Zunming Lu,Xinghua Zhang
Designing catalysts that simultaneously optimize both hydrogen and oxygen evolution reaction (HER and OER) emerges as a critical materials challenge. Co(OH)₂ is recognized as an effective OER electrocatalyst, but the low HER activity limits its application in overall water splitting. In this work, we synthesized sulfur (S) and selenium (Se) doped Co(OH) 2 catalysts with significantly enhanced HER activity using an electrochemical deposition method. The S-Co(OH) 2 and Se-Co(OH) 2 catalysts own low HER overpotentials of 48 mV and 59 mV at 10 mA cm −2 . And they require 1.56 V and 1.64 V at the same current density for water splitting, the sustain stable performance for > 100 h at current densities (100 mA cm −2 ) show their practical durability. Density Functional Theory (DFT) calculations and experimental results reveal that non-metal doping induces electronic reconfiguration of Co and optimizes the ΔG H* value for intermediate formation, thus accelerating hydrogen generation and enhancing the intrinsic HER activity. This work presents an effective strategy for incorporating non-metal elements into transition metal-based catalysts, and provides insight to boost HER intrinsic activity and achieve bifunctional catalytic performance for water splitting.
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Biomaterials Advances
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2025
·
IF 6
Long Yang,Yufei Liu,Yong Yang,Yuhu Zhou,Zihao Zou,Min He,Changlei Yang,Daizhu Yuan,Jieheng Wu,Chuan Ye
Artificial bone substitutes have garnered significant attention within the field of biomaterials, and the use of tissue engineering technology to repair bone defects has emerged as a promising alternative. However, when artificial bone substitutes are implanted in the body, they can induce many adverse cellular and tissue immune responses. In this study, we use coaxial electrospinning technology to fabricate microfiber with controllable diameter, excellent mechanical properties and surface porous structure. Poly(3-hydroxybutyrate- co -4-hydroxybutyrate) (P34HB) and polyethylene glycol (PEG) were used as shell solutions and polyvinyl alcohol (PVA) and bone morphogenetic protein-2 (BMP-2) peptides as core solutions. Compared to PVA/P34HB-PEG (P/P-P) scaffolds, PVA-BMP-2/P34HB-PEG (P-B/P-P) scaffolds polarized more human monocytic leukemia cell line (THP-1 cells) toward alternatively activated macrophages (M2), as demonstrated by increased M2 and decreased classically activated macrophage (M1) phenotypic marker expression in the cells. P-B/P-P microfibers have the potential to regulate the polarization state of macrophages, induce them to differentiate into an M2 phenotype and inhibit the inflammatory response of surrounding tissues. In addition, microfibers with a hollow porous structure facilitate the controlled release of BMP-2 peptides by regulating the fiber diameter, enhancing the differentiation of pre-osteoblastic cell line derived from mouse calvaria (MC3T3-E1) cells in an osteogenic direction and facilitating the repair of bone defects in vivo. This study presents microfibers essential for modulating the osteoimmune microenvironment, facilitating efficient bone regeneration.
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BMC MUSCULOSKELETAL DISORDERS
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2024
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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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Catalysts
·
2025
·Vol. 15
·期 9
·826
·
IF 4
Anran Zhu,Zhufan Zou,Yu Cong,Yinghua Yin,Ning Li
A novel two-step strategy was developed for the efficient synthesis of decalin and octahydroindene from lignocellulose-derived platform compounds. In the first step, bicyclic intermediates were directly generated via a cascade dehydration/Robinson annulation of 4-hydroxy-2-butanone with cyclohexanone (or cyclopentanone). Among the evaluated catalysts, CaO demonstrated the highest activity and selectivity. Based on CO2-TPD results, the excellent performance of CaO can be rationalized by its proper basicity. In the second step, these intermediates were selectively hydrodeoxygenated to decalin (or octahydroindene) over Ni/H-ZSM-5 catalyst. Under the investigated reaction conditions, ~90% overall yields of decalin and octahydroindene were achieved. This work provides a viable strategy for the selective conversion of lignocellulose-derived platform compounds to the additives for improving the thermal stability of aviation fuel.
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PEST MANAGEMENT SCIENCE
·
2025
·
IF 3.8
Hamza Tariq,Peiyu Chen,Gang Wang,Siyuan Xie,Lanning Wang,Jingkun Lv,Fei Wang,Muhammad Saqib Bilal,Abdur Rashid Khan,Nasir Ahmed Rajput,Danyu Shen,Daolong Dou
BACKGROUND Alternaria alternata is a globally distributed plant pathogen infecting >400 plant species. Trans -2-decenal is a notable plant-derived secondary metabolite with strong volatility and antifungal properties, although its specific activity and mode-of-action against A. alternata remain unclear. RESULTS Toxicity assays showed that trans -2-decenal inhibited A. alternata with a median inhibitory concentration (IC 50 ) of 12.23 mg L −1 . Treated with trans -2-decenal resulted in hyphal abnormalities, reduced spore production and suppressed spore germination. Mechanistically, it disrupted fungal cell membrane integrity, as confirmed by propidium iodide staining and increased leakage of DNA and soluble proteins in conductivity assays. Further investigations revealed that trans -2-decenal disrupted redox homeostasis by inducing reactive oxygen species (ROS) accumulation. DCFH-DA fluorescence staining showed elevated ROS levels, whereas antioxidant enzyme assays revealed dose-dependent changes, including decreased superoxide anion (O 2 . − ) and catalase (CAT) activity, and significantly increased hydrogen peroxide (H 2 O 2 ), superoxide dismutase (SOD) and malondialdehyde (MDA) levels, collectively indicating oxidative stress and damage. Transcriptome analysis identified 2319 differentially expressed genes (DEGs), with gene ontology (GO) enrichment highlighting inhibition of pathways associated with oxidative stress response, transmembrane transport and ribosome biogenesis. Molecular docking further suggested interactions between trans -2-decenal and key antioxidant enzyme and membrane transporter of A. alternata . In vivo assays showed that 32 mg L −1 trans -2-decenal fumigation achieved protective and curative efficacies of 97.14% and 96.54%, respectively, against yam leaf spot disease. CONCLUSION Trans -2-decenal inhibited A. alternata through a multitarget synergistic mechanism, providing theoretical support for its development as a plant-derived biofumigant and a promising tool for the green management of A. alternata -induced diseases. © 2025 Society of Chemical Industry.
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Nature Cancer
·
2025
·
IF 28.5
Han Jinpeng,Wang Shenqiang,Fang Weifeng,Yang Yinxian,Zhou Ruyi,Zhang Yuqi,Yu Jicheng,Tang Ruikang,Liu Zhaoming,Gu Zhen
Long-acting controlled drug release formulations are highly desired for potentiating efficacy and reducing administration frequency. Here we present a kinetically controllable long-term interleukin-2 (IL-2) release platform by the fusion and boundary elimination of calcium carbonate and calcium phosphate amorphous phases. Unlike mixtures, a group of hybrid biominerals with the chemical formula Ca(CO 3 ) x (PO 4 ) 2(1− x )/3 (CaCPs, 0 < x < 1) was fabricated under high pressure (2 GPa), and the CaCPs showed crystallization-driven release behaviors to optimize the in vivo fate of IL-2. Ca(CO 3 ) 1/2 (PO 4 ) 1/3 dynamically remodeled immunosuppressive tumor microenvironments, preferentially activated cytotoxic and memory T cells by improving IL-2 redistribution and achieved weeks-long IL-2 retention in tumors with high tolerance and biosafety. In a melanoma model in female mice, Ca(CO 3 ) 1/2 (PO 4 ) 1/3 revealed superior antitumor effects to inhibit local tumor recurrence, hinder the growth of distant untreated tumors and maintain long-term T cell responses against the rechallenged metastatic tumors.
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ADVANCED MATERIALS
·
2025
·
IF 26.8
Anquan Zhu,Heng Liu,Lulu Qiao,Bin Liu,Kunlun Liu,Chuhao Luan,Kai Liu,Yin Zhou,Dewu Lin,Guoqiang Gan,Jiapei Li,Guo Hong,Wenjun Zhang
The electrochemical nitrate reduction reaction (eNO 3 RR) is widely recognized as a promising strategy for sustainable ammonia production and supporting the nitrogen cycle. However, its advancement is impeded by complex behavior of reaction intermediates and the inevitable reconstruction of precatalysts. To address these challenges, the generation and utilization of active hydrogen (*H) are strategically managed by tailoring the RuO 2 /Co 3 O 4 precatalyst and optimizing the electrolyte composition (OH − and NO 3 − concentration), thereby selectively enhancing ammonia formation. Consequently, the in situ reconstructed RuO 2 /Co(OH) 2 catalyst achieves an impressive ammonia yield of 35.9 ± 0.9 mg h −1 cm −2 and a Faradaic efficiency (FE) of 98.1 ± 2.6% at −0.3 V versus RHE. Furthermore, the catalyst shows significant potential for applications in nitrate-rich wastewater treatment and rechargeable Zn-NO 3 − batteries, maintaining stable operation for over 260 hours at 1 mA cm −2 with only a 6 mV increase in the potential window. Mechanistic studies reveal that electron-rich RuO 2 facilitates *H generation through water dissociation, which subsequently migrates to Co(OH) 2 to hydrogenate nitrogenous intermediates, selectively producing ammonia. This study highlights the importance of designing efficient catalytic systems that address both precatalyst reconstruction and the complexities of reactant and intermediate conversion in electrolytes, which are essential for managing the intricate electron and proton transfer processes involved in eNO 3 RR.
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