JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2025
·
IF 6.2
Xiaozan Dai,Guanchen Liu,Quan Zhang,Chao Zhu,Huipeng Gao,Youduo Wu,Chi Cheng,Hailong Lin,Chuang Xue
The fungus Trichoderma reesei is widely employed for industrial enzyme production. However, the mechanisms coordinating enzyme production with amino acid biosynthesis and metabolism remain incompletely understood. Here, we characterized a novel C2H2 zinc finger transcription factor, TrTRC-1, in T. reesei. The deletion of TrTRC-1 enhanced cellulase, xylanase, and extracellular protein production by 9.8–32.4% compared to that in T. reesei Rut C30, while simultaneously stimulating mycelial growth and conidiation. Transcriptomic analysis revealed that the deletion of TrTRC-1 significantly altered the expression of genes associated with primary metabolic pathways, amino acid biosynthesis/metabolism, and carbohydrate-active enzymes. In a 5 L bioreactor, T. reesei ΔTrTRC-1 achieved an FPase activity of 17.35 IU/mL and exhibited robust saccharification efficiency on lignocellulosic biomass. These findings demonstrate that TrTRC-1 serves as a multifunctional regulator in T. reesei, advancing our understanding of the regulatory network that balances enzyme production with cellular metabolism and providing a strategic basis for constructing microbial chassis strains with industrial application prospects.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CNS Neuroscience & Therapeutics
·
2025
·Vol. 31
·期 12
·e70654
·
IF 5
Yulong Liu,Meiling Xia,Xinggao Zhang,Jing Luo,Tianyao Liu,Hong Gong,Jiayin Liu,Mei Chen,Lian Wang,Jinghui Zhao,Meifeng Gong,Yi Luo,Xiaotang Fan
Background Naringin, a flavanone glycoside (naringenin 7-O-neohesperidose), exhibits a broad range of pharmacological activities, including neuroprotection. However, its effects on autistic-like behavior have not been extensively studied. Methods In this investigation, we utilized the autistic BTBR T + tf/J (BTBR) mice to conduct behavioral tests assessing autistic-like phenotypes. We evaluated hippocampal neurogenesis through immunofluorescence and employed molecular biological techniques, along with RNA sequencing, to elucidate the underlying molecular mechanisms. Results Our findings revealed that the administration of naringin alleviated autism-associated behaviors in BTBR mice. RNA sequencing analysis indicated that naringin facilitated the recovery of impaired hippocampal neurogenesis in these mice, as evidenced by an increase in doublecortin (DCX)-positive cells and neuronal progenitor cells (NPCs) in the dentate gyrus (DG). Furthermore, we confirmed that the cannabinoid receptor type-1 (CB1) plays a role in the therapeutic effects of naringin. Conclusions This research highlights the potential of naringin as a promising treatment option for autism spectrum disorder (ASD) and suggests that targeting hippocampal neurogenesis through the CB1 receptor may be an effective strategy.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MEDICINAL CHEMISTRY RESEARCH
·
2019
·Vol. 28
·期 9
·1388-1401
·
IF 1.72
Chen Xin,Liu Xiujie,Qiu kai,Xu Xiang,Li Caiwen,Wang Yan
According to the bio-isosterism theory, a series of N , N ’-disubstitutedphenyl-4-ethoxylbenzene-1, 3-disulfonamides ( 5a - p ) were designed and synthesized by two steps of reactions including chlorosulfonation and ammonolysis. The structures of all compounds have been confirmed by IR, 1 H-NMR, 13 C-NMR, and ESI-MS spectra. The in vitro anti-platelet aggregation activities were evaluated by Born’s test induced by adenosine diphosphate (ADP) and arachidonic acid (AA), respectively. The biological evaluation results revealed that compound 5h had the lowest IC 50 value (0.32 μM) and the highest inhibition rate (40.9 %) that of three positive control agents clopidogrel (0.41 μM, 23.5 %), aspirin (0.53 μM, 28.9 %), and picotamide (0.76 μM, 32.7 %). Afterwards, compounds with higher activities were selected to further study in vitro cytotoxicity via cell counting kit-8 (CCK-8) assay. The cytotoxicity results indicated that compound 5h had simultaneously the lowest cytotoxicity, while other compounds had no significant relationship between the anti-platelet activities and cytotoxicities. Based on above in vitro anti-platelet activity data, the SAR (Structure Activity Relationship) of the target compounds was preliminarily summarized. In general, N , N ’-disubstitutedphenyl-4-ethoxylbenzene-1, 3-disulfonamides have the potential of further study and very likely become safer and more effective anti-platelet agents.
✓ 已验证
DOI
高影响因子
Polymers
·
2025
·Vol. 18
·期 1
·64
·
IF 4.9
Ruijun Zhang,Ziyi Dong,Qiqi He,Junhua Li,Yuexin Hu,Jianhua Qian
Accurate knowledge of phase behavior in polyolefin–solvent mixtures is critical for ensuring stable operation and safe scale-up of industrial solution polymerization processes. The binary (n-hexane + ethylene/1-octene copolymer, POE96k-10) and ternary (α-olefin +n-hexane + POE96k-10) phase behaviors were investigated via a visual high-pressure cell (POE96k-10:Mw= 96 kg·mol–1,Mw/Mn= 3.87, 1-octene mole fraction = 10.31 mol%) at temperatures of 380~480 K and pressures as high as 14 MPa. To systematically analyze the effects of α-olefin mass fraction and type on phase transition, four industrially relevant α-olefins (ethylene, 1-butene, 1-hexene, and 1-octene) were investigated. The results show that the phase transition temperature and pressure for liquid–liquid and liquid–vapor transitions show an approximately linear dependence on α-olefin mass fraction. Ethylene, 1-butene, and 1-hexene lower the phase transition temperature, whereas 1-octene increases it. Ethylene exhibits a strong anti-solvent effect, significantly lowering the transition temperature while increasing the phase transition pressure. The modified Sanchez-Lacombe equation of state (MSL EOS) effectively correlates and reproduces the phase equilibrium data of the α-olefin +n-hexane + POE96k-10 ternary systems, though its accuracy decreases with increasing α-olefin chain length.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2021
·
IF 5.811
Liu Yang,Tang Liang-Liang,Liang Chen,Wu Ming-Ming,Zhang Zhi-Ren
Antiangiogenic tyrosine kinases inhibitors induce hypertension, which may increase the incidents of cardiovascular complications and limit their use. However, the mechanisms by which usage of TKIs results in hypertension have not been fully understood. Here, we report the potential mechanisms of how sunitinib, a widely used TKI, induces hypertension. Male SD rats were randomly divided into control group and sunitinib-administrated group. We show that sunitinib administration for seven days caused a significant increase in artery blood pressure, along with glycerolipid metabolism abnormalities including decreased food intake and low body weight, hypoglycemia, hyperinsulinemia. Sunitinib administration also resulted in a significant increase in the levels of insulin autoantibody (IAA), cyclic adenosine monophosphate and free fatty acid in serum; whereas, sunitinib administration had no effects on serum glucagon levels. Sunitinib led to the decreased insulin sensitivity as determined by insulin tolerance test (ITT) and glucose tolerance test (GTT), reflecting insulin resistance occurred in sunitinib-treated rats. The results obtained from wire myograph assay in the mesenteric arteries show that endothelium-dependent relaxation, but not endothelium-independent relaxation, was impaired by sunitinib. Furthermore, western blot analysis revealed that the expressions levels of phosphorylated IRS-1, Pellino-1, AKT and eNOS were significantly attenuated by sunitinib in rat mesenteric artery tissues and in the sunitinib-treated primary cultured mesenteric artery endothelial cells. The levels of serum and endothelium-derived nitric oxide were also significantly decreased by sunitinib. Moreover, sunitinib-induced decrease in the expression levels of phosphorylated AKT and eNOS was further reduced by knocking down of Pellino-1 in MAECs. Our results suggest that sunitinib causes vascular dysfunction and hypertension, which are associated with insulin resistance- and Pellino-1-mediated inhibition of AKT/eNOS/NO signaling. Our results may provide a rational for preventing and/or treating sunitinib-induced endothelial dysfunction and hypertension.
✓ 已验证
DOI
PubMed
高影响因子
CELLULAR AND MOLECULAR LIFE SCIENCES
·
2023
·Vol. 80
·期 3
·1-16
·
IF 8
Li Xiaoxue,Zhang Yumeng,Chang Jianghao,Zhang Chenglin,Li Lin,Dai Yifan,Yang Haiyuan,Wang Ying
Previous studies have shown that mfat-1 transgenic mice have protective effects against some central nervous system (CNS) disorders, owing to the high docosahexaenoic acid (DHA) content enriched in their brains. However, whether this protective effect is connected to the blood – brain barrier (BBB) remains unclear. This study aims to investigate the mechanisms of the protective effect against hypoxic-ischemic brain damage (HIBD) of mfat-1 transgenic mice. mfat-1 mice not only demonstrated a significant amelioration of neurological dysfunction and neuronal damage but also partly maintained the physiological permeability of the BBB after HIBD. We initially showed this was associated with elevated major facilitator superfamily domain-containing 2a (Mfsd2a) expression on the BBB, resulting from more lysophosphatidylcholine (LPC)-DHA entering the brain. Wild-type (WT) mice showed a similar Mfsd2a expression trend after long-term feeding with an LPC-DHA-rich diet. Knockdown of Mfsd2a by siRNA intra-cerebroventricular (ICV) injection neutralized the protective effect against HIBD-induced BBB disruption in mfat-1 mice, further validating the protective function of Mfsd2a on BBB. HIBD-induced BBB high permeability was attenuated by Mfsd2a, primarily through a transcellular pathway to decrease caveolae-like vesicle-mediated transcytosis. Taken together, these findings not only reveal that mfat-1 transgenic mice have higher expression of Mfsd2a on the BBB, which partly sustains BBB permeability via vesicular transcytosis to alleviate the severity of HIBD, but also suggest that dietary intake of LPC-DHA may upregulate Mfsd2a expression as a novel therapeutic strategy for BBB dysfunction and survival in HIBD patients.
✓ 已验证
DOI
PubMed
高影响因子
CHEMICO-BIOLOGICAL INTERACTIONS
·
2019
·
IF 3.407
Jialin Xu,Leilei Zhou,Qi Weng,Linxia Xiao,Qingyong Li
Beta-amyloid (Aβ) has pivotal functions in the pathogenesis of Alzheimer's Disease (AD). In the present study, we adopted an vitro model that involved Aβ 25-35 -induced oxidative damage in PC12 cells. Aβ 25-35 (10 μΜ) treatment for 24 h induced significant cell death and oxidative stress in PC12 cells, as evidenced by cell viability reduction, LDH release, ROS accumulation and increased production MDA . (1E,4E)-1, 5-bis(4-hydroxy-3-methoxyphenyl) penta-1, 4-dien-3-one (CB) and (1E, 4E)-1-(3, 4-dimethoxyphenyl)-5-(4-hydroxy-3, 5-dime-thoxyphenyl) Penta-1, 4-dien-3-one (FE), two Curcumin (Cur) analogues displayed neuroprotective effects against Aβ 25-35 -induced oxidative damage and cellular apoptosis in PC12 cells. Here, we investigated three different treatment ways of CB and FE. It was interesting that post-treatment of CB and FE (restoring way) showed similar effect to the preventive way, while attenuating way did not show any protective effect. We found that low dose CB and FE increased transcriptional factor NF-E2-related factor 2 (Nrf2)/hemo oxygenase 1 (HO-1) protein expression and decreased Kelch-like ECH-associated protein 1 (Keap1) in PC 12 cells. In addition, CB and FE promoted the translation of Nrf2 into nuclear and enhanced the activity of superoxide dismutase (SOD)/catalase, which confirmed cytoprotection against Aβ 25-35 -induced oxidative damage. Moreover, CB and FE could increase Bcl-2 expression level, decrease the level of Bax and Cyt-c in Aβ 25-35 -treated PC12 cells. Ultimately, the neuroprotective effect of CB and FE provides a pharmacological basis for its clinical use in prevention and treatment of AD.
✓ 已验证
DOI
PubMed
高影响因子
iScience
·
2022
·
IF 6.107
Jiajun Liu,Ting Li,Ge Wang,Jiahuan Chen,Qingqing Yao,Qian Li,Xinfeng Zhao
Summary Methods of immobilized proteins are challenged by the way how to capture the proteins in their intact functional states. Here we present a two-point, high-specific method for the immobilization of conformationally specific angiotensin II type 1 receptor (AT 1 R) on amino-functionalized polystyrene microspheres. We identified a selective DNA aptamer of AT 1 R by a column-based SELEX approach with micromolar affinity. Two single-stranded DNA strands were utilized to introduce the AT 1 R aptamer and angiotensin II 3-8 peptide to the microsphere surface, resulting in the two surface-positioned sites. The two-point immobilized AT 1 R exhibited enhanced ligand-binding activity and stability in comparison with that prepared by a one-positioned site. Ginsenoside Rg1 and rosmarinic acid were screened from the herbal extract and proved to bind with AT 1 R through the allosteric and orthosteric sites of the receptor, respectively. These provide a generally applicable approach for functional protein immobilization with enhanced conformation stability, ligand binding activity, and screening efficiency.
✓ 已验证
DOI
PubMed
高影响因子
Experimental and Therapeutic Medicine
·
2022
·Vol. 24
·期 1
·1-8
·
IF 2.751
Maoshun Tang,Yi Zheng,Jianping Li,Yuanlang Hu
Venous endothelial cell apoptosis can be induced by endoplasmic reticulum (ER) stress, thus serving an important role in the formation of deep venous thrombosis. X‑box binding protein 1 (XBP1) is a protein associated with ER. The present study aimed to explore the function of XBP1/C/EBP homologous protein (CHOP) pathway in the process of endothelial cell apoptosis under hyperglycemia. Small interfering (si)RNAs targeting XBP1 and CHOP were designed to downregulate the expression of XBP1 and CHOP in human umbilical vein endothelial cell, respectively. Flow cytometry was used to determine cell apoptosis. The expression of XBP1, glucose‑regulated protein 78 (GRP78), CHOP, Puma, cleaved caspase‑3 and Cytochrome c was evaluated by western blotting. There were seven groups of cells that were used in the present study: i) Control (5.5 mM D‑glucose); ii) hypertonic (hypertonic control, 27.8 mM mannitol and 5.5 mM D‑glucose); iii) 16.7 mM D‑glucose; iv) 33.3 mM D‑glucose; v) 33.3 mM + NC (33.3 mM D‑glucose incubated with NC); vi) 33.3 mM + si‑XBP1 (33.3 mM D‑glucose incubated with siRNA against XBP1); and vii) 33.3 mM + si‑CHOP (33.3 mM D‑glucose incubated with siRNA against CHOP). Compared with the control, the apoptosis rate of human umbilical vein endothelial cells (HUVECs) increased greatly with the increase in the concentration of D‑glucose. Compared with the 33.3 mM D‑glucose group, the HUVECs incubated with 33.3 mM D‑glucose and si‑XBP1 or 33.3 mM D‑glucose and si‑CHOP demonstrated a significantly lower apoptosis rate. Compared with the control, XBP1, GRP78, CHOP, Puma, cleaved caspase‑3 and cytochrome c were significantly upregulated in the hypertonic, 16.7 mM D‑glucose, 33.3 mM D‑glucose and 33.3 mM + negative control (NC) groups. Compared with the 33.3 mM D‑glucose group, the expression levels of XBP1, GRP78, CHOP, Puma, cleaved caspase‑3 and cytochrome c in the 33.3 mM + si‑XBP1 or 33.3 mM + si‑CHOP groups significantly decreased. High dosage of glucose induced endothelial cell apoptosis by promoting the expression of apoptotic proteins by activating endoplasmic reticulum stress. XBP1/CHOP may be a potential target for the treatment of deep vein thrombosis as one of the key pathways regulating ERS by regulating apoptosis of endothelial cells.
✓ 已验证
DOI
PubMed
高影响因子
Cell Reports
·
2023
·
IF 8.8
Qianyu Yang,Huaxing Dai,Ying Cheng,Beilei Wang,Jialu Xu,Yue Zhang,Yitong Chen,Fang Xu,Qingle Ma,Fang Lin,Chao Wang
Nanoplastics (NPs) as contaminants in food and water have drawn increasing public attention. However, little is known about how NPs shape the gut immune landscape after injection. In this study, we fabricate NPs (∼500 nm) and microplastics (MPs) (∼2 μm) and evaluate their in vivo effects by feeding them to mice. The results suggest that NPs show a better ability to induce gut macrophage activation than MPs. In addition, NPs trigger gut interleukin-1 (IL-1)-producing macrophage reprogramming via inducing lysosomal damage. More importantly, IL-1 signaling from the intestine can affect brain immunity, leading to microglial activation and Th17 differentiation, all of which correlates with a decline in cognitive and short-term memory in NP-fed mice. Thus, this study provides insight into the mechanism of action of the gut-brain axis, delineates the way NPs reduce brain function, and highlights the importance of fixing the plastic pollution problem worldwide.
✓ 已验证
DOI
PubMed
高影响因子
Science of Advanced Materials
·
2014
·Vol. 6
·期 9
·1936-1942
·
IF 2.908
Li Xiang,Ding Xuelian,Wang Gongke,Zhou Yixuan,Hou Ruipeng,Gao Shuyan,Lu Yan
In this work, we have developed a simple and highly sensitive fluorescent biosensor for the detection of HIV-1 RNase H activity and inhibition by using graphene oxide (GO) as sensing platform. In our approach, a DNA-RNA substrate was prepared which a carboxy fluorescein (FAM) was labeled
at the 3 termini of single strand DNA. The FAM labeled DNA-RNA substrate preserves most of the fluorescence when mixed with GO. However, in the present of RNase H, RNase H can cleavage the RNA into fragments, resulting in the dissociation of ssDNA and mononucleotides. The fluorescence intensity
was greatly quenched after the addition of GO. Because of the super quenching ability of GO, the as-proposed method provides a wide linear range from 1.0 to 26.3 units mL–1 and a low detection limit of 0.6 units mL–1 for HIV-1 RNase H activity analysis. Additionally,
this approach shows potential for high-throughput screening of HIV-1 RNase H inhibitors. The method not only provides a universal platform for monitoring activity and inhibition of RNase H but also shows great potential in biological process researches, drug discovery, and clinic diagnostics.
✓ 已验证
DOI
高影响因子
Oxidative Medicine and Cellular Longevity
·
2021
·
IF 6.543
Haiwen Zhang,Youming Liu,Xin Fang,Lihong Gu,Caiwei Luo,Lu Chen,Qian Wang
Vitamin D 3 , as an indispensable and fat-soluble micronutrient, plays an important role in the health of humans and animals. At present, studies are focusing on the calcium absorption and immunoregulation function of vitamin D 3 ; this study was aimed at exploring the antioxidative stress ability of vitamin D 3 on diquat-induced intestinal dysfunction of ICR mice and the underlying mechanism. The results showed that oral gavage of vitamin D 3 daily significantly improved the body weight gain and immune organ index and significantly reverted the abnormal changes of ALT, AST, SOD, GSH-Px, T-AOC, and MDA in the serum and jejunum induced by diquat. The addition of vitamin D 3 also significantly reduced the concentration of DAO, D-LA, and certain proinflammatory cytokines in serum. Moreover, vitamin D 3 improved the pathological morphology of the duodenum, jejunum, colon, liver, and kidney tissues, and it also largely attenuated the degree of inflammatory infiltration of macrophages and cell apoptotic index of jejunal epithelial tissue induced by diquat. The results demonstrated that vitamin D 3 significantly recovered the intestinal barrier injury by enhancing the expression of mucins and tight junction proteins in the jejunum. In addition, the results indicated that vitamin D 3 could significantly reduce the phosphorylation level of NF- κ B (p65) and enhance the expression of Nrf2 and HO-1 in the jejunum compared with the diquat-induced group. This study suggested that oral administration of vitamin D 3 can protect mice against oxidative damage by inhibiting the phosphorylation level of NF- κ B (p65) and activating Nrf2-related signaling pathways.
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）