C Allele of the PPARδ+294T>C Polymorphism Confers a Higher Risk of Hypercholesterolemia, but not Obesity and Insulin Resistance: A Systematic Review and Meta-Analysis.

The relationships of the PPARα Leu162Val and PPARδ+294 T>C polymorphisms with metabolic indexes have been reported to be inconsistent and even contradictory. The meta-analysis was conducted to clarify the relationships between the two variants and the indexes of obesity, insulin resistance, and blood lipids. PubMed, Google Scholar, Embase, and Cochrane Library were searched for eligible studies. Standardized mean difference with 95% confidence interval was calculated to estimate the differences in the metabolic indexes between the genotypes of the Leu162Val and+294 T>C polymorphisms. Heterogeneity among studies was assessed by Cochran's x2-based Q-statistic test. Publication bias was identified by using Begg's test. Forty-one studies (44 585 subjects) and 33 studies (23 018 subjects) were identified in the analyses for the Leu162Val and+294 T>C polymorphisms, respectively. C allele carriers of the+294 T>C polymorphism had significantly higher levels of total cholesterol and low-density lipoprotein cholesterol than TT homozygotes in the whole population. Notably, C allele carriers of the+294 T>C polymorphism had significantly higher levels of triglycerides and total cholesterol in East Asians, but lower levels of triglycerides in West Asians than TT homozygotes. Regarding the Leu162Val polymorphism, it was found that Val allele carriers had significantly higher levels of blood glucose than Leu/Leu homozygotes only in European Caucasians. The meta-analysis demonstrates that C allele of the+294 T>C polymorphism in PPARδ gene confers a higher risk of hypercholesterolemia, which may partly explain the relationship between this variant and coronary artery disease.

Intelligent Manufacturing Technology in the Steel Industry of China: A Review.

Intelligent manufacturing, defined as the integration of manufacturing with modern information technologies such as 5G, digitalization, networking, and intelligence, has grown in popularity as a means of boosting the productivity, intelligence, and flexibility of traditional manufacturing processes. The steel industry is a necessary support for modern life and economic development, and the Chinese steel industry's capacity has expanded to roughly half of global production. However, the Chinese steel industry is now confronted with high labor costs, massive carbon emissions, a low level of intelligence, low production efficiency, and unstable quality control. Therefore, China's steel industry has launched several large-scale intelligent manufacturing initiatives to improve production efficiency, product quality, manual labor intensity, and employee working conditions. Unfortunately, there is no comprehensive overview of intelligent manufacturing in China's steel industry. We began this research by summarizing the construction goals and overall framework for intelligent manufacturing of the steel industry in China. Following that, we offered a brief review of intelligent manufacturing for China's steel industry, as well as descriptions of two typical intelligent manufacturing models. Finally, some major technologies employed for intelligent production in China's steel industry were introduced. This research not only helps to comprehend the development model, essential technologies, and construction techniques of intelligent manufacturing in China's steel industry, but it also provides vital inspiration for the manufacturing industry's digital and intelligence updates and quality improvement.

Nanoscale zero-valent iron/magnetite carbon composites for highly efficient immobilization of U(VI).

Nanoscale zerovalent iron/magnetic carbon (NZVI/MC) composites were successfully synthesized by simply calcining yellow pine and iron precursors. NZVI/MC pyrolyzed at 800°C (NZVI/MC800) had a higher percentage of NZVI and displayed better resistance to aggregation and oxidation of NZVI than samples prepared at other temperatures. The NZVI/MC800 material was applied for the elimination of U(VI) from aqueous solutions. The results suggested that the NZVI/MC800 displayed excellent adsorption capacity (203.94 mg/g) toward U(VI). The significant adsorption capacity and fast adsorption kinetics were attributed to the presence of well-dispersed NZVI, which could quickly reduce U(VI) into U(IV), trapping the guest U(IV) in the porous biocarbon matrix. The removal of U(VI) on the NZVI/MC samples was strongly affected by solution pH. The NZVI/MC samples also displayed outstanding reusability for U(VI) removal after multiple cycles. These findings indicate that NZVI/MC has great potential for remediation of wastewater containing U(VI).

The novel PEI-modified biochars and their application for the efficient elimination of Cr(VI) from aqueous solutions.

In this study, the polyethyleneimine (PEI) was grafted onto the biochars from chestnut shells and nori via the cross-linking reaction. Scanning electron microscopy, transmission electron microscopy and Fourier transferred infrared spectroscopy analysis indicated that the PEI was successfully grafted on the surface of biochars. The PEI modified and pristine biochars were used as adsorbents to remove Cr(VI) from aqueous solutions as a function of pH, ionic strength, contact time and initial concentrations of Cr(VI) through batch technique. The strongly pH-dependent and ionic strength-independent of Cr(VI) sorption indicated that the sorption was mainly dominated by electrostatic interaction and inner-sphere surface complexation. The maximum sorption capacities of PEI modified chestnut shell and nori biochars were 141.42 and 222.84 mg/g, respectively, which were significantly higher than those of pristine biochars. The PEI grafted onto the biochars significantly enhanced Cr(VI) sorption capacity because PEI, which contains volumes of amine/imine groups, provided an excellent platform for Cr(VI) ions removal. In addition, the sorption-desorption experimental results indicated that the PEI modified biochars possessed a stable and recyclable performance. All these results manifested that the PEI modified biochars could be applied as environmentally friendly and efficient adsorbents for the removal of Cr(VI) from wastewater.

Co-targeting CDK 4/6 and C-MYC/STAT3/CCND1 axis and inhibition of tumorigenesis and epithelial-mesenchymal-transition in triple negative breast cancer by Pt(II) complexes bearing NH3 as trans-co-ligand.

In search of potential anticancer agents, we synthesized SNO-donor salicylaldimine main ligand-based Pt(II) complexes bearing NH3 as co-ligand at trans-position (C1-C6). These complexes showed similarity in structure with transplatin as the two N donor atoms of the main ligand and NH3 co-ligand were coordinated to Pt in trans position to each other. Each complex with different substituents on the main ligand was characterized thoroughly by detailed spectroscopic and spectrophotometric methods. Four of these complexes were studied in solid state by single crystal X-ray analysis. The stability of reference complex C1 was measured in solution state in DMSO­d6 or its mixture with D2O using 1H NMR methods. These complexes were further investigated for their anticancer activity in triple-negative-breast (TNBC) cells including MDA-MB-231, MDA-MB-468 and MDA-MB-436 cells. All these complexes showed satisfactory cytotoxic effect as revealed by the MTT results. Importantly, the highly active complex C4 anticancer effect was compared to the standard chemotherapeutic agents including cisplatin, oxaliplatin and 5-fluorouracil (5-FU). Functionally, C4 suppressed invasion, spheroids formation ability and clonogenic potential of cancer cells. C4 showed synergistic anticancer effect when used in combination with palbociclib, JQ1 and paclitaxel in TNBC cells. Mechanistically, C4 inhibited cyclin-dependent kinase (CDK)4/6 pathway and targeted the expressions of MYC/STAT3/CCND1/CNNE1 axis. Furthermore, C4 suppressed the EMT signaling pathway that suggested a role of C4 in the inhibition of TNBC metastasis. Our findings may pave further in detailed mechanistic study on these complexes as potential chemotherapeutic agents in different types of human cancers.

Salicylaldehyde-derived piperazine-functionalized hydrazone ligand-based Pt(II) complexes: inhibition of EZH2-dependent tumorigenesis in pancreatic ductal adenocarcinoma, synergism with PARP inhibitors and enhanced apoptosis.

Piperazine is an important functional unit of many clinically approved drugs, including chemotherapeutic agents. In the current study, methyl piperazine was incorporated and eight salicylaldehyde-derived piperazine-functionalized hydrazone ONN-donor ligands (L) and their Pt(II) complexes (L-PtCl) were prepared. The structures of all these ligands (L1-L8) and Pt(II) complexes (C1-C8) were determined using 1H and 13C NMR, UV-vis, FT-IR and HR-ESI MS analyses, whereas the structures of C1, C5, C6, C7 and C8 were determined in the solid state using single crystal X-ray diffraction analysis. Solution state stabilities of C3, C4, C5 and C6 were determined via time-dependent UV-vis spectroscopy. All these complexes (C1-C8) were studied for their anticancer effect in pancreatic ductal adenocarcinoma cells, including BxPC3, MIAPaCa-2 and PANC1 cells. C1-C8 displayed a potential cytotoxic effect in all these cancer cells, among which C5, C6 and C8 showed the strongest inhibitory effect in comparison with standard chemotherapeutic agents, including 5-fluorouracil (5-FU), cisplatin (CP), oxaliplatin and doxorubicin (DOX). C5, C6 and C8 suppressed the growth of pancreatic cancer cells in a dose-dependent manner. Moreover, C5, C6 and C8 inhibited clonogenic potential and invasion ability and induced apoptosis in PANC1 cells. Importantly, C5, C6 and C8 synergized the anticancer effect with PARP inhibitors, including olaparib, veliparib and niraparib, in pancreatic cancer cells, thus suggesting an important role of C5, C6 and C8 in induction of apoptosis in combination with PARP inhibitors. C5 combined with PARP inhibitors induced caspase3/7 activity and suppressed ATP production. Mechanistically, C5, C6 and C8 inhibited EZH2 protein expression to suppress EZH2-dependent tumorigenesis. Overall, these results highlighted the importance of these piperazine-functionalized Pt(II) complexes as potential anticancer agents to suppress pancreatic ductal adenocarcinoma tumorigenesis by targeting the EZH2-dependent pathway.

Chemical synthesis of oligosaccharides and their application in new drug research.

Oligosaccharides are the ubiquitous molecules of life. In order to translate human bioglycosylation into clinical applications, homogeneous samples of oligosaccharides and glycoconjugates can be obtained by chemical, enzymatic or other biological methods for systematic studies. However, the structural complexity and diversity of glycans and their conjugates present a major challenge for the synthesis of such molecules. This review summarizes the chemical synthesis methods of oligosaccharides, the application of oligosaccharides in the field of medicinal chemistry according to their related biological activities, and shows the great prospect of oligosaccharides in the field of pharmaceutical chemistry.

Facet-dependent U(VI) removal of hematite with confined ferrous ions.

The presence of ferrous minerals has been demonstrated to have a significant impact on the destiny, migration, and availability of uranyl (U(VI)) in natural surroundings. The iron oxide/Fe(II) system is a multifaceted iron reduction system anchored to surfaces, encompassing various forms of iron and ferrous ions. Several studies have investigated the effectiveness of adsorbed ferrous iron on iron-based minerals to facilitate the reduction of heavy metal ions and radioactive nuclides. A range of techniques for characterization, including X-ray photoelectron spectroscopy (XPS) and Mössbauer spectroscopy, were employed to explore the process of U(VI) adsorption and deposition, focusing on the limited region containing ferrous iron on the exposed crystalline surface of hematite. In this specific investigation, two kinds of hematite nanocrystals primarily exposing {001} and {012} crystal facets, referred to as HNPs and HNCs, were synthesized. Their ability to remove U(VI) was examined. Ferrous ions (Fe(II)) adsorbed onto the surface of hematite nanocrystals significantly enhanced the efficiency of U(VI) remediation. Furthermore, the HNCs/Fe(II) system showed better U(VI) reduction ability than the HNPs/Fe(II) system. Remarkably, HNCs produced and consumed more electrons and hydroxyl radicals, indicating a more intense response. This finding serves to highlight the significance of their role in interfacial effects and in predicting the spatial distribution of U(VI) in aqueous systems.

Monofunctional dimetallic Ru(η6-arene) complexes inhibit NOTCH1 signaling pathway and synergistically enhance anticancer effect in combination with cisplatin or vitamin C.

ONS donor ligands L1-L4 were utilized in the preparation of monofunctional dimetallic Ru(η6-arene) complexes (C1-C4). These ONS donor ligand based novel tricoordinated Ru(II) complexes bearing η6-arene co-ligand were prepared for the first time. The current methodology resulted in excellent isolated yields and these complexes were characterized in detail by different spectroscopic and spectrometric techniques. The structures of C1-C2 and C4 were characterized in solid state by single crystal X-ray analysis. The in vitro anticancer analyses showed these novel complexes suppressed the growth of breast (MCF-7), liver (HepG2) and lung (A549) cancer cells. C2 suppressed the growth of these cells in dose-dependent manner revealed form the MTT and crystal violet cell viability assays. Moreover, C2 was observed the most potent complex that was used further in detailed mechanistic analyses in cancer cells. C2 showed good cytotoxic activity at 10 µM dose level as compared to cisplatin or oxaliplatin in these cancer cells. We observed morphological changes in cancer cells upon treatment with C2. Moreover, C2 suppressed the invasion and migration ability of cancer cells. C2 induced cellular senescence to retard cell growth and suppressed the formation of cancer stem cells. Importantly, C2 showed synergistic anticancer effect in combination with cisplatin and Vitamin C to further inhibit cell growth which suggested the potential role of C2 in cancer therapy. Mechanistically, C2 inhibited NOTCH1 dependent signaling pathway to suppress cancer cell invasion, migration and cancer stem cells formation. Thus, these data suggested potential role of C2 in cancer therapy by targeting NOTCH1-dependent signaling to suppress tumorigenesis. The results obtained in this study for these novel monofunctional dimetallic Ru(η6-arene) complexes showed their high anticancer potency and this study will pave to further cytotoxicity exploration on this class of complexes.

Inhibition of SREBP-mediated lipid biosynthesis and activation of multiple anticancer mechanisms by platinum complexes: Ascribe possibilities of new antitumor strategies.

Cancer is one of the most aggressive diseases with poor prognosis and survival rates. Lipids biogenesis play key role in cancer progression, metastasis and tumor development. Suppression of SREBP-mediated lipid biogenesis pathway has been linked with cancer inhibition. Platinum complexes bearing good anticancer effect and multiple genes activation properties are considered important and increase the chances for development of new platinum-based drugs. In this study, we synthesized pyridine co-ligand functionalized cationic complexes and characterized them using multiple spectroscopic and spectrophotometric methods. Two of these complexes were studied in solid state by single crystal X-ray analysis. The stability of these complexes were measured in solution state using 1H NMR methods. These complexes were further investigated for their anticancer activity against human breast, lung and liver cancer cells. MTT assay showed potential cytotoxic activity in dose-dependent manner and decrease survival rates of cancer cells was observed upon treatment with these complexes. Biological assays results revealed higher cytotoxicity as compared to cisplatin and oxaliplatin. Further we studied C2, C6 and C8 in detailed mechanistic anticancer analyses. Clonogenic assay showed decrease survival of MCF-7, HepG2 and A549 cancer cells treated with C2, C6 and C8 as compared to control cells treated with DMSO. TUNEL assay showed more cell death, these complexes suppressed invasion and migration ability of cancer cells and decreased tumor spheroids formation, thus suggesting a potential role in inhibition of cancer metastasis and cancer stem cells formation. Mechanistically, these complexes inhibited sterol regulatory element-binding protein 1 (SREBP-1) expression in cancer cells in dose-dependent manner and thereby reduced lipid biogenesis to suppress cancer progression. Furthermore, expression level was decreased for the key genes LDLR, FASN and HMGCR, those required for sterol biosynthesis. Taken together, these complexes suppressed cancer cell growth, migration, invasion and spheroids formation by inhibiting SREBP-1 mediated lipid biogenesis pathway.

Platinum complexes inhibit HER-2 enriched and triple-negative breast cancer cells metabolism to suppress growth, stemness and migration by targeting PKM/LDHA and CCND1/BCL2/ATG3 signaling pathways.

Triple-negative-breast cancer (TNBC) and HER-2 enriched positive aggressive types of breast cancer and are highly metastatic in nature. Anticancer agents those target TNBC and HER-2 enriched positive breast cancers are considered important in the field of breast cancer research. In search of the effective anticancer agents, we synthesized Pt(II) complexes to target these cancers. Platinum complexes (C1-C8) were prepared in single step by the reaction of commercially available K2PtCl4 with the readily prepared ligands (L1-L8). All these compounds were characterized successfully by different spectroscopic and spectrophotometric analyses. Structures of C1, C3 and C8 were characterized by single crystal X-ray analysis that confirmed the exact chelation mode of the SNO-triply coordinated ligand. All these complexes inhibited the in vitro growth of MCF-7 (luminal-like), MDA-MB-231 (TNBC) and SKBR3 (HER-2 enriched) breast cancer cells. C1, C3 and C7 induced cell death and suppressed the clonogenic potential of these cancer cells. Importantly, C1, C3 and C7 showed potentials to suppress cancer stem cells/mammosphere formation and cell migration ability of MDA-MB-231 and SKBR3 breast cancer cells. These complexes also induced cellular senescence in MDA-MB-231 and SKBR3 cells, thus suggesting a cell retardation mechanism. Similarly, these complexes induced DNA damage by activating p-H2AX expression and promoted autophagy via ATG3/LC3B axis activation in MDA-MB-231 and SKBR3 cells. Furthermore, these complexes decreased the expression of oncogenic proteins such as BCL2 and cylin-D1 those are involved in cancer cell survival and cell cycle progression. To further gain insight, we found that C1 and C7 targeted glycolytic pathways by regulating PKM and LDHA expression, which are involved in glycolysis. Moreover, C1 and C7 suppressed the formation of ATP production that is required for cancer cell growth. Taken together, the easy synthesis and biological assays results point towards the importance of these complexes in MDA-MB-231 (TNBC) and SKBR3 (HER-2 enriched) breast cancer cells by targeting multiple signaling pathways those are considered important during breast cancer progression. This study produces bases for further deeper in vitro or in vivo study that could lead to the effective breast cancer agents which we are working on.

Efficient capture of ReO4- on magnetic amine-functionalized MIL-101(Cr): Revealing from selectivity to mechanism.

The efficient decontamination of pertechnetate (99TcO4-) is an essential task for managing radioactive 99Tc in nuclear wastes. Perrhenate, (ReO4-), as a nonradioactive analog, exhibits almost identical physicochemical properties as 99TcO4-. Herein, a novel magnetic amine-functionalized MIL-101(Cr) (NH2-MIL-101(Cr)@Fe3O4) was prepared and used to efficiently remove ReO4- from solution for the facile magnetic separation. A series of environmental parameters were considered to investigate the adsorption performance of NH2-MIL-101(Cr)@Fe3O4. Experimental results suggested that NH2-MIL-101(Cr)@Fe3O4 has reached a satisfied adsorption capacity (~401 mg/g) and a very fast adsorption kinetics at pH 7.0. The selectivity for ReO4- was maintained even in the presence of interfering anions with relatively high concentrations. ReO4- were mainly captured by N-donor sites of the surface-decorated amine via complexation and were trapped in the cavities of modified MIL-101(Cr). NH2-MIL-101(Cr)@Fe3O4 exhibits satisfactory adsorption performance for ReO4- and can be conveniently separated from wastewaters after adsorption.

Enhanced removal of uranium(VI) from aqueous solution by a novel Mg-MOF-74-derived porous MgO/carbon adsorbent.

The elimination and safe treatment of U(VI) from radioactive wastewater has attracted widespread attention with the development of the nuclear power industry. In this work, a MgO/carbon adsorbent was successfully prepared by one-step Mg-MOF-74 pyrolyzation and used for U(VI) removal from aqueous solution. Characteristic results indicated that the as-prepared composite was a typical porous structure. The adsorption performance of the MgO/carbon towards U(VI) was studied by batch experiments. The results indicated that the MgO/carbon can rapidly and effectively remove U(VI) and showed an excellent adsorption capacity (777.51 mg/g), which is much higher than other reported adsorbent materials. In addition, the intraparticle diffusion model provides a good explanation for each adsorption process. The adsorption capacity of the MgO/carbon towards U(VI) is greatly promoted by the large specific surface area and well-defined porous structure. Based on the zeta potential and XPS analysis, the possible mechanism for U(VI) removal involved the surface complexation and electrostatic attraction. The results indicate that the MgO/carbon can be regarded as an efficient adsorbent for U(VI) removal from wastewater, which has a very broad application prospect.

Exploration of the adsorption performance and mechanism of zeolitic imidazolate framework-8@graphene oxide for Pb(II) and 1-naphthylamine from aqueous solution.

A novel composite of zeolitic imidazolate framework grown on graphene oxide (ZIF-8@GO) was successfully prepared and used for the adsorption of Pb(II) and 1-naphthylamine from aqueous solutions. The effects of contact time, pH, ionic strength and temperature on the adsorption performance of ZIF-8@GO was investigated by batch experiments. Compared to the bare ZIF-8 and GO, the ZIF-8@GO exhibited a significant increase in the adsorption for Pb(II) and 1-naphthylamine. The maximum adsorption capacities of ZIF-8@GO towards Pb(II) and 1-naphthylamine reached 356.0 and 171.3 mg/g at 293 K, respectively. Besides, the basic physicochemical properties of ZIF-8@GO were characterized by Scanning electron microscope, X-ray diffraction, and Fourier transform infrared spectroscopy tests. The results revealed that ZIF-8@GO had large specific surface area, abundant functional groups and active sites on the surface, which could promote the adsorption of ZIF-8@GO for pollutants. In addition, based on zeta potential and X-ray photoelectron spectroscopy analysis, the primary adsorption mechanisms between ZIF-8@GO and Pb(II) were the surface complexation and electrostatic attraction, and the π-π interactions mainly contributed to the adsorption of 1-naphthylamine. In conclusion, as a new composite, ZIF-8@GO provides a reference idea for the removal of heavy metal ions and organic pollutants from water system.

Targeted thrombolysis strategies for neuroprotective effect.

Stroke is usually treated by systemic thrombolytic therapy if the patient presents within an appropriate time window. There is also widespread interest in the development of thrombolytic agents that can be used in cases of delayed presentation. Current agents that can be used in cases of delayed presentation of nerve damage by thrombus. Current systemic thrombolytic therapy is associated with adverse effects such as fibrinogenolysis and bleeding. In an attempt to increase the efficacy, safety, and specificity of thrombolytic therapy, a number of targeted thrombolytic agents have been studied in recent years. This review focuses on the concepts underlying targeted thrombolytic therapy and describes recent drug developments in this field.