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JOURNAL OF APPLIED PHYCOLOGY · 2023 · IF 3.3

Efficient preparation and production of ulvan oligosaccharides by using a new PL25 family ulvan lyase from Alteromonas sp. 76–1

Tang Tiancheng,Li Chen,Zhu Benwei,Yao Zhong

Ulvan lyase is a useful tool which can degrade ulvan into oligosaccharides with a range of biological activities. In this study, the ulvan lyase ULA-3 from Alteromonas sp. 76–1, which was a 1467-bp encoded 489-amino acid residue protein, has been cloned, heterologously expressed and biochemically characterized. ULA-3 showed the maximum activity at 45 ˚C and pH 9.0. The K m is 1.879 mg mL −1 and V max is 2.597 µmol min −1  mL −1 . Its enzyme activity was outstanding at 11.754 U mg −1 . Moreover, its metal ion stability is exceptionally good and most metal ions at a concentration of 1 mM have no inhibitory effect on its activity. It can endolytically degrade ulvan into oligosaccharides with a degree of polymerization (Dp) of 2–4 and with unsaturated double bond through the β -elimination reaction, which mainly cleaves the glycosidic bond between rhamnose and uronic acids. All in all, our study has increased the ulvan lyase database and offers the opportunity to fully utilize ulvan, a green biomass resource from marine algae.

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SOLAR ENERGY MATERIALS AND SOLAR CELLS · 2023 · IF 6.9

Electrochromic conjugated polymers containing benzotriazole and thiophene performing sub-second response time and 916 cm2 C−1 superb coloration efficiency

Changjun Wu,Hong Chen,Jingru Tan,Danna Zhou,Haoshen Liang,Shijie Zhen,Hao Liu,Yuehui Wang,Kaiwen Lin

In pursuit of high-performance electrochromic conjugated polymers (ECPs), three benzotriazole-thiophene ECPs employing benzotriazole as acceptor and different thiophene repeating units as donors, namely, PBTz-T, PBTz-BT, and PBTz-TT, were synthesized via direct (hetero)arylation polymerization (DHAP). Meanwhile, following the above ECPs model, we investigated the effect of corresponding conjugated chain length of monomers on their optical, electrochemical and electrochromic properties. The results showed that along with the increase of the numbers of thiophene in the repeating unit of ECPs, the electronic and optical band gaps decreased, the UV–Vis absorption and fluorescence spectra showed significant bathochromic shift, and the electrochemical cycle stability gradually improved. PBTz-T exhibited giant coloration efficiency (916 cm 2  C −1 at 530 nm), which is one of the best results in the visible region. And higher coloration efficiency means less energy consumption, which holds great potential for various applications, including electrochromic back covers of smartphones. PBTz-BT displayed the highest transmittance (28% at 550 nm), and BTz-TT illustrated the fastest switching time (0.6 s/0.5 s for doping/dedoping process). Flexible electrochromic device (ECD) fabricated employed PBTz-T as functional layer gradually changed from red (reduction) to dark green (oxidation), and maintained good cycling stability.

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HUMAN GENE THERAPY · 2023 · IF 4.2

Direct Knockdown of PDZ and LIM Domain 1 Using an Adenoviral Delivery System Accelerates Osteogenesis and Fracture Healing in Mice

Dr. Zhiguang Chen,Ms. Qi Zhao,Mr. Ran Zhang,Dr. Lianghong Chen,Mr. Songlan Gao,Dr. Yu Wang,Dr. Tiegang Li,Dr. Jinqi Xue

Substantial advances have been made in understanding the role of partial PDZ and LIM domain (PDLIM) family’s proteins in skeletal-related diseases. Yet, little is known about the effect of Pdlim1 on osteogenesis and fracture repair. This study aimed to investigate whether direct gene delivery using an adenovirus vector carrying Pdlim1 (Ad-oePdlim1) or encoding shRNA-Pdlim1 (Ad-shPdlim1) could affect the osteogenic activity of pre-osteoblastic MC3T3-E1 cells in vitro, and influence the fracture healing of mice in vivo. We found that Ad-shPdlim1 transfection contributed to the calcified nodule formation in MC3T3-E1 cells. Downregulation of Pdlim1 enhanced the alkaline phosphatase (ALP) activity and increased the expression of osteogenic markers (Runx2, Col1A1, osteocalcin and osteopontin). Further analysis indicated that Pdlim1 knockdown could activate β-catenin signaling, as evidenced by the accumulation of β-catenin in the nucleus and the increase levels of downstream regulators such as Lef1/Tcf7, Axin2, Cyclin D1 and Sox9. By contrast, Pdlim1 overexpression resulted in inhibition of the osteogenic activity of MC3T3-E1 cells. In vivo, at day 3 after fracture, Ad-shPdlim1 adenovirus particles were injected into the fracture site of the femur of mice, and the process of fracture healing was evaluated by X-ray, Micro-CT and histological examination. Local injection of Ad-shPdlim1 promoted the early cartilage callus formation, restored bone mineral density and accelerated cartilaginous ossification, with the upregulation of osteogenic gene (Runx2, Col1A1, osteocalcin and osteopontin) expression and activation of β-catenin signaling. Thus, we concluded that inhibition of Pdlim1 contributed to osteogenesis and fracture healing by activating the β-catenin signaling pathway.

CAS / MDL: 50-81-7 47165-04-8
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Experimental and Therapeutic Medicine · 2023 ·Vol. 26 ·期 1 ·1-10 · IF 2.7

CRP‑1 promotes the malignant behavior of hepatocellular carcinoma cells via activating epithelial‑mesenchymal transition and Wnt/β‑catenin signaling

Shixiong Lei,Xilin Du,Kai Tan,Xiaojun He,Yejing Zhu,Shoujie Zhao,Zhenyu Yang,Gang Dou

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. It has been reported that cysteine rich protein 1 (CRP‑1) is dysregulated in several types of human cancer; however, its role in HCC is poorly understood. Therefore, the current study aimed to investigate the role of CRP‑1 in HCC. Western blotting and reverse transcription‑quantitative PCR results showed that CRP‑1 was upregulated in HCC cell lines. Furthermore, for in vitro experiments, CRP‑1 was knocked down and overexpressed in the HCC cell lines Hep 3B2.1‑7 and BEL‑7405, respectively. c‑Myc and proliferating cell nuclear antigen upregulation, and cleaved caspase 3 and poly(ADP‑ribose) polymerase downregulation suggested that CRP‑1 silencing could inhibit the proliferation and colony‑forming ability of HCC cells, and induce apoptosis. In addition, CRP‑1 overexpression promoted the malignant behavior of HCC cells and induced epithelial‑mesenchymal transition (EMT), as verified by E‑cadherin downregulation, and N‑cadherin and vimentin upregulation. Additionally, CRP‑1 overexpression promoted the nuclear translocation of β‑catenin, and activated the expression of cyclin D1 and matrix metalloproteinase‑7. Furthermore, inhibition of Wnt/β‑catenin signaling, following cell treatment with XAV‑939, an inhibitor of the Wnt/β‑catenin signaling pathway, abrogated the effects of CRP‑1 on enhancing the proliferation and migration of HCC cells. These findings indicated that the regulatory effect of CRP‑1 on HCC cells could be mediated by the Wnt/β‑catenin signaling pathway. Overall, CRP‑1 could promote the proliferation and migration of HCC cell lines, partially via promoting EMT and activating the Wnt/β‑catenin signaling pathway.

CAS / MDL: 30525-89-4 28718-90-3
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Drug Design Development and Therapy · 2023 · IF 4.8

Cinchonine, a Potential Oral Small-Molecule Glucagon-Like Peptide-1 Receptor Agonist, Lowers Blood Glucose and Ameliorates Non-Alcoholic Steatohepatitis

Huan Xue,Hao-Jie Xing,Bin Wang,Chao Fu,Yu-Shan Zhang,Xi Qiao,Chao Guo,Xiao-Li Zhang,Bin Hu,Xin Zhao,Li-Jiao Deng,Xiao-Chan Zhu,Yi Zhang,Yun-Feng Liu

Purpose The glucagon-like peptide-1 receptor (GLP-1R) is an effective therapeutic target for type 2 diabetes mellitus (T2DM) and non-alcoholic steatohepatitis (NASH). Research has focused on small-molecule GLP-1R agonists because of their ease of use in oral formulations and improved patient compliance. However, no small-molecule GLP-1R agonists are currently available in the market. We aimed to screen for a potential oral small-molecule GLP-1R agonist and evaluated its effect on blood glucose and NASH.Methods The Connectivity map database was used to screen for candidate small-molecule compounds. Molecular docking was performed using SYBYL software. Rat pancreatic islets were incubated in different concentrations glucose solutions, with cinchonine or Exendin (9–39) added to determine insulin secretion levels. C57BL/6 mice, GLP-1R−/− mice and hGLP-1R mice were used to conduct oral glucose tolerance test. In addition, we fed ob/ob mice with the GAN diet to induce the NASH model. Cinchonine (50 mg/kg or 100 mg/kg) was administered orally twice daily to the mice. Serum liver enzymes were measured using biochemical analysis. Liver tissues were examined using Hematoxylin-eosin staining, Oil Red O staining and Sirius Red staining.Results Based on the small intestinal transcriptome of geniposide, a recognized small-molecule GLP-1R agonist, we identified that cinchonine exerted GLP-1R agonist-like effects. Cinchonine had a good binding affinity for GLP-1R. Cinchonine promoted glucose-dependent insulin secretion, which could be attenuated significantly by Exendin (9–39), a specific GLP-1R antagonist. Moreover, cinchonine could reduce blood glucose in C57BL/6 and hGLP-1R mice, an effect that could be inhibited with GLP-1R knockout. In addition, cinchonine reduced body weight gain and food intake in ob/ob-GAN NASH mice dose-dependently. 100 mg/kg cinchonine significantly improved liver function by reducing the ALT, ALP and LDH levels. Importantly, 100 mg/kg cinchonine ameliorated hepatic steatosis and fibrosis in NASH mice.Conclusion Cinchonine, a potential oral small-molecule GLP-1R agonist, could reduce blood glucose and ameliorate NASH, providing a strategy for developing small-molecule GLP-1R agonists.

CAS / MDL: 118-10-5 485-71-2
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ACS Applied Energy Materials · 2023 · IF 6.4

Low-Cost and Simple Synthesis of Dispersed CsPbBr3 Perovskite Single-Crystal Wires with Lengths over 1 mm Using Bernoulli’s Principle

Ronghuan Liu,Bihua Hu,Kai Wang,Baomin Xu,Xiao Wei Sun

Compared with polycrystalline thin films, perovskite single crystals without grain boundaries have better photovoltaic performance and stability. However, due to the extremely low solubility of all-inorganic perovskite in organic solvents and the complex phase diagram of CsPbBr3, directly growing large-sized CsPbBr3 perovskite single-crystal wires is challenging. Here, we have developed an airflow-assisted growth method for the rapid synthesis of large quantities of high-quality, dispersed, ultralong CsPbBr3 single-crystal wires under ambient conditions. This method is green (no additives) and low cost (no special treatment). The growth kinetics of single-crystal wires using this method have been elucidated, and their structural and optoelectronic properties were characterized. Some of the CsPbBr3 single-crystal wires synthesized by this method can exceed 1 mm in length with a low trap density of about 9.06 × 1011 cm–3. The constructed photodetector responsivity is up to 0.365 A/W and detectivity is over 3.3 × 1013 Jones, indicating great potential for optoelectronic applications. This low-cost, high-quality all-inorganic CsPbBr3 single-crystal wire growth method is highly scalable and may facilitate the research and application of all-inorganic perovskite single crystals.

CAS / MDL: 67-68-5
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MATERIALS & DESIGN · 2023 · IF 8.4

Construction of nicotinic acid curcumin nanoparticles and its Anti-atherosclerosis effect via PCSK9/LDL-R, ABCA1/Caveolin-1/LXR pathway

Chao-ping He,Wen-juan Quan,Ya-ling Zeng,Hong-yan Zhou,Pei-dong You,Zhen-xian Li,Ya-mei Li,Li-mei Lin,Bin Liu,Duan-fang Liao,Qin-hui Tuo

Reducing lipid uptake of macrophages and stimulating cholesterol efflux are two necessary steps for atherosclerotic plaque regression. In this study, a compound of curcumin nicotinate (CN) was synthesized from nicotinic acid which can raise raising high-density lipoprotein (HDL) and curcumin which can lower lipid. However, the shortcomings of CN, such as poor water solubility and low bioavailability, limit its clinical application. In this article, a CN loaded biomimetic nanosystem was constructed by using Prussian blue nanoparticles (PB NPs) to improve its solubility, thereby changing its administration route. In addition, hyaluronic acid (HA) modification on the biomimetic PB NPs was adopted to prolong circulation time and improve the accumulation of drugs in the plaque region. Mechanism studies have shown that the constructed nanosystem could exert anti-AS effects through the pathway of Proprotein Convertase Subtilisin/Kexin Type 9(PCSK9) /Low-density lipoprotein receptor (LDL-R), ATP Binding Cassette Transporter A1(ABCA1) /Caveolin-1 /Liver X Receptor (LXR). These findings indicated that the designed nano-platform is expected to be used for prevention and targeted therapy of atherosclerosis.

CAS / MDL: 458-37-7 59-67-6
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DIGESTIVE DISEASES AND SCIENCES · 2023 · IF 3.1

Karyopherin Subunit Alpha 1 Enhances the Malignant Behaviors of Colon Cancer Cells via Promoting Nuclear Factor-κB p65 Nuclear Translocation

Zhao Lianrong,Wu Di,Qu Qiao,Li Zhilong,Yin Hongzhuan

Background/Aims Aberrant nuclear factor-κB p65 (NF-κB p65) nuclear import commonly occurs in multiple cancers, including colon cancer. According to BioGRID, we noted that Karyopherin subunit alpha 1 (KPNA1), an important molecular transporter between the nucleus and the cytoplasm, may interact with NF-κB p65. KPNA1 itself is highly expressed in colon adenocarcinoma samples ( N  = 286) based on The Cancer Genome Atlas (TCGA) database. We aimed to explore the role of KPNA1 in colonic carcinogenesis and to determine whether NF-κB p65 nuclear translocation was involved. Methods KPNA1 expressions at mRNA and protein levels were analyzed in colon cancer tissues. The regulatory effect of KPNA1 on malignant biological properties was detected in SW480 and HCT116 colon cancer cells. Coimmunoprecipitation and immunofluorescence were performed to verify the relationship between KPNA1 and NF-κB p65. KPNA1 ubiquitination was also preliminarily investigated. Results KPNA1 was firstly confirmed as a significantly upregulated gene in our collected clinical colon cancer samples ( N  = 35). KPNA1 depletion inhibited cell proliferation, induced cell cycle arrest, and diminished migratory and invasive capacity of SW480 and HCT116 cells. Colon cancer cells overexpressing KPNA1 acquired more aggressive behaviors. KPNA1 acted as a transporter to induce the nuclear accumulation of NF-κB p65, thereby activating NF-κB signaling pathway in colon cancer cells. Furthermore, HECT, C2, and WW Domain-Containing E3 Ubiquitin (HECW2) interacted with KPNA1 to induce its ubiquitination. KPNA1 labeled with polyubiquitins was degraded through ubiquitin–proteasome system. Conclusion The present study uncovers a role of KPNA1-NF-κB p65 axis in promoting colonic carcinogenesis. Graphical Abstract

CAS / MDL: 47165-04-8
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EUROPEAN JOURNAL OF PHARMACOLOGY · 2023 · IF 5

Puerarin protects against sepsis-associated encephalopathy by inhibiting NLRP3/Caspase-1/GSDMD pyroptosis pathway and reducing blood-brain barrier damage

Shuang Zhou,Yuhua Li,Yi Hong,Zhitao Zhong,Min Zhao

Puerarin (Pue), an isoflavone compound extracted from Pueraria, has been shown to inhibit inflammation and reduce cerebral edema. The neuroprotective effect of puerarin has attracted much attention in recent years. Sepsis-associated encephalopathy (SAE) is a serious complication of sepsis that causes damage to the nervous system. This study aimed to investigate the effect of puerarin on SAE and elucidate the potential underlying mechanisms. A rat model of SAE was established by cecal ligation and puncture, and puerarin was injected intraperitoneally immediately after the operation. Puerarin was found to improve the survival rate and neurobehavioral score of SAE rats, alleviate symptoms, inhibit the level of brain injury markers NSE and S100β, and improve the pathological changes in rat brain tissue. Puerarin was also found to inhibit the level of factors related to the classical pathway of pyroptosis, such as NLRP3, Caspase-1, GSDMD, ASC, IL-1β, and IL-18. Puerarin also reduced the brain water content and penetration of Evan’s Blue dye in SAE rats, and reduced the expression of MMP-9. In the in vitro experiments, we further confirmed the inhibitory effect of puerarin on neuronal pyroptosis by establishing a pyroptosis model in HT22 cells. Our findings suggest that puerarin may improve SAE by inhibiting the classical pathway of NLRP3/Caspase-1/GSDMD-mediated pyroptosis and reducing blood-brain barrier damage, thus playing a role in brain protection. Our study may provide a novel therapeutic strategy for SAE.

CAS / MDL: 75-12-7
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CHEMICAL ENGINEERING JOURNAL · 2023 · IF 15.1

Persulfate activation by Fe3O4-doped biochar synthesized from Fenton sludge and sewage sludge for enhanced 1-H-1,2,4-triazole degradation

Siqi Tong,Dan Chen,Xinbai Jiang,Zhixiang Xu,Xiaodong Liu,Jinyou Shen

A novel composite biochar synthesized from Fenton sludge (FS) and sewage sludge (SS) was employed to catalyze persulfate for the removal of 1-H-1,2,4-triazole (TZ). The optimized conditions for the synthesis and operating process were identified through response surface methodology as follow: SS/FS mass ratio = 5:1, catalyst dosage = 0.9 g L −1 and PDS concentration = 0.5 g L −1 . The removal efficiencies of TZ, TOC and organic nitrogen were found to be as high as 97.6%, 80.33% and 100%, respectively, with the addition of Fe 3 O 4 -doped biochar in persulfate catalytic system. Besides, Fe 3 O 4 -doped biochar exhibited superior stability and tolerance to wide range of pH (2–12), temperature (15–45 °C) and co-existing substrate. The reactive oxygen species, which resulted in the catalytic degradation of TZ followed the order of SO 4 ∙− > ∙OH > O 2 ∙− > 1 O 2 , were identified by electron spin resonance and quenching tests. It demonstrated that the radical pathway accomplished with non-radical pathway contributed to the enhanced degradation of TZ, which was further identified by electrochemical experiments. Moreover, the possible degradation pathway of TZ was ascertained and proposed through DFT calculation and LC-MS analysis. These findings illustrated that the novel magnetic biochar would be a promising persulfate catalyst for the treatment of refractory organic matters. In addition, it also provided a new alternative method for the resource utilization of FS and SS.

CAS / MDL: 106-51-4 98-00-0 75-65-0
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Acta Biomaterialia · 2023 · IF 9.7

Genetically engineered PD-1 displaying nanovesicles for synergistic checkpoint blockades and chemo-metabolic therapy against non-small cell lung cancer

Bo Li,Tong Yang,Jin Liu,Xixi Yu,Xinying Li,Fei Qin,Jiefei Zheng,Jinxia Liang,Youyan Zeng,Zhenhua Zhou,Lu Liu,Bin Zhang,Weiwei Yao,Zhuo Feng,Guandi Zeng,Qian Zhou,Liang Chen

Non-small cell lung cancer (NSCLC) remains the most frequently diagnosed lung cancer and the leading cause of cancer-related mortality worldwide. PD-1/PD-L1 axis inhibitors have changed the treatment paradigm for various cancer types, including NSCLC. However, success of these inhibitors in lung cancer clinic is severely limited by their inability to inhibit the PD-1/PD-L1 signaling axis due to heavy glycosylation and heterogeneity expression of PD-L1 in NSCLC tumor tissue. Taking advantage of the facts that tumor cell derived nanovesicles could efficiently accumulate in the homotypic tumor sites due to their innate targeting abilities and that specific and high affinity existed between PD-1 and PD-L1, we developed NSCLC targeting biomimetic nanovesicles (NV) cargos from genetically engineered NSCLC cell lines that overexpressed PD-1 (P-NV). We showed that P-NVs efficiently bound NSCLC cells in vitro and targeted tumor nodules in vivo . We further loaded P-NVs with 2-deoxy-D-glucose (2-DG) and doxorubicin (DOX), and found that these drugs co-loaded P-NVs efficiently shrank lung cancers in mouse models for both allograft and autochthonous tumor. Mechanistically, drug-loaded P-NVs efficiently caused cytotoxicity to tumor cells and simultaneously activated anti-tumor immunity function of tumor-infiltrating T cells. Our data therefore strongly argue that 2-DG and DOX co-loaded, PD-1-displaying nanovesicles is a highly promising therapy for treatment of NSCLC in clinic. Statement of significance Lung cancer cells overexpressing PD-1 are developed for preparing nanoparticles (P-NV). PD-1s displayed on NVs enhance their homologous targeting abilities to tumor cells expressing PD-L1s. Chemotherapeutics such as DOX and 2-DG, are packaged in such nanovesicles (PDG-NV). These nanovesicles efficiently delivered chemotherapeutics to tumor nodules specifically. The synergy between DOX and 2-DG is observed in inhibiting lung cancer cells in vitro and in vivo . Importantly, 2-DG causes deglycosylation and downregulation of PD-L1 on tumor cells while PD-1 displayed on nanovesicles’ membrane blocks PD-L1 on tumor cells. 2-DG loaded nanoparticles thus activate anti-tumor activities of T cells in the tumor microenvironment. Our work thus highlights the promising antitumor activity of PDG-NVs, which warrants further clinical evaluation.

CAS / MDL: 25316-40-9
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COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS · 2023 · IF 5.2

Corrosion inhibition effect of 1-phenyl-5-mercaptotetrazole on nickel-aluminum bronze in seawater: A combined experimental and theoretical study

Jinyu Pi,Mengjin Chen,Tianqi Chen,Qi Wang,Shijian Cheng,Chaoyang Fu

A combined experimental and theoretical study was performed on corrosion inhibition effect of 1-Phenyl-5-mercaptotetrazole (PMT) on nickel-aluminum bronze (NAB) in seawater . Gravimetric measurement and electrochemical method, such as the open circuit potential (OCP), electrochemical impedance spectroscopy (EIS), Tafel polarization curve were used to verify the corrosion inhibition effect of PMT. It was found that the corrosion inhibition efficiency (IE) of PMT achieved 94.4 %, 99.5 %, 98.7 % at a concentration of 1.12 mM, respectively. The slump of the degree of corrosion on NAB surface was also revealed based on SEM and AFM images analysis with the addition of PMT. According to the Langmuir isotherm model based on EIS, PMT was confirmed as a mixed-type corrosion inhibitor between −20 kJ mol –1 and −40 kJ mol –1 . Besides, the successful adsorption of PMT on NAB has been revealed by the results of XPS and the change of water contact angle on NAB surface. In combination XPS with quantum chemistry calculations, PMT molecules are adsorbed on the surface of NAB by the active S atom and the tetrazole ring as the major adsorption groups, thus, the protective barrier formed by PMT on the surface of NAB can effectively insulate NAB from contact with seawater. The research results in this paper have showed that PMT as a drug intermediate has an excellent corrosion inhibition effect on the NAB at extremely low concentration in seawater.

CAS / MDL: 64-17-5
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