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Selective catalytic reduction (SCR) systems are important technical means of mitigating NOx emissions for diesel engines. The major challenge of this technique is to improve the low-temperature act...

A template-free strategy was designed to prepare hierarchical porous carbons (HPCs) using fluid catalytic cracking oil modified a coal tar pitch (CTP). The resulting HPCs possess large specific surface areas, reasonable pore size distributions, and wrinkled structures, which could improve the overall electrochemical performance. They exhibit a specific capacitance value of 329 F g−1 at 0.5 A g−1 and still maintain 220 F g−1 at 20 A g−1, manifesting the remarkable rate capability. Additionally, the assembled symmetrical supercapacitor delivers a highest energy density of 23.6 Wh kg−1 at a power density of 500 W kg−1 and outstanding cycle stability of 92.8% capacitance retention after 10000 cycles. This work paves a new way to fabricate advanced carbon materials from low-cost CTP and provides a promising approach for value-added utilization of CTP.

Hyperlipidemia is one major cause of atherosclerosis, which is a basic pathological change of cardiovascular diseases. Polysaccharide is a water-soluble component with lipid-lowering effects. In this study, alkaline-extracted polysaccharides were obtained from the fruiting body of C. militaris. Polysaccharides were purified via anion exchange and size exclusion chromatography. Their structural characteristics were investigated via chemical and spectroscopic methods. CM3I was mainly composed of →4)α-D-Glcp(1 → glycosyls and differed from starch due to the presence of →4,6)β-D-Glcp(1 → glycosyls. CM3II was characterized by its backbone, which was composed of →4)-β-D-Manp(1 → 6)-α-D-Manp(1 → 6)-β-D-Manp(1 → linked glycosyls, and especially the presence of O-methyl. Moreover, CM3II exhibited powerful anti-atherosclerotic effects via lowering plasma lipid levels in apolipoprotein E-deficient mice. The underlying mechanisms were attributed to its promoting effect on LXRα and inhibitory effect on SREBP-2. Collectively, CM3I and CM3II are different from the previously reported polysaccharides from C. militaris, and CM3II has a potential application in hypolipidemia and anti-atherosclerosis.

Ischemia/reperfusion (I/R) injury is a major cause of acute kidney injury (AKI) in clinic. The activation of NLRP3 inflammasome is associated with inflammation and renal injury in I/R-induced AKI. In the current study we explored the molecular and cellular mechanisms for NLRP3 inflammasome activation following renal I/R. Mice were subjected to I/R renal injury by clamping bilateral renal pedicles. We showed that I/R injury markedly increased caspase-11 expression and the cleavage of pannexin 1 (panx1) in the kidneys accompanied by NLRP3 inflammasome activation evidenced by the activation of caspase-1 and interlukin-1β (IL-1β) maturation. In Casp-11(−/−) mice, I/R-induced panx1 cleavage, NLRP3 inflammasome activation as well as renal functional deterioration and tubular morphological changes were significantly attenuated. In cultured primary tubular cells (PTCs) and NRK-52E cells, hypoxia/reoxygenation (H/R) markedly increased caspase-11 expression, NLRP3 inflammasome activation, IL-1β maturation and panx1 cleavage. Knockdown of caspase-11 attenuated all those changes; similar effects were observed in PTCs isolated from Casp-11(−/−) mice. In NRK-52E cells, overexpression of caspase-11 promoted panx1 cleavage; pretreatment with panx1 inhibitor carbenoxolone or knockdown of panx1 significantly attenuated H/R-induced intracellular ATP reduction, extracellular ATP elevation and NLRP3 inflammasome activation without apparent influence on H/R-induced caspase-11 increase; pretreatment with P2X7 receptor inhibitor AZD9056 also attenuated NLRP3 inflammasome activation. The above results demonstrate that the cleavage of panx1 by upregulated caspase-11 is involved in facilitating ATP release and then NLRP3 inflammasome activation in I/R-induced AKI. This study provides new insight into the molecular mechanism of NLRP3 inflammasome activation in AKI.

The activation of Wnt/β‐catenin pathway plays a pivotal role in promoting renal fibrosis. The activation of Wnt/β‐catenin pathway relies on the binding of Wnts to Frizzled receptors on cell membrane. However, the factor regulating Wnts production remains unclear. Here, we demonstrated that transcriptional factor FoxM1 was significantly increased in obstructed kidneys and patients' kidneys with fibrosis. The up‐regulation of FoxM1 mainly distributed in tubular epithelial cells. Pharmacological inhibition of FoxM1 down‐regulated multi‐Wnts elevation in UUO mice and attenuated renal fibrosis. In cultured renal tubular epithelial cells, overexpression of FoxM1 promoted 8 Wnts expression, while knock‐down on FoxM1‐suppressed multi‐Wnts including Wnt1, Wnt2b and Wnt3 expression induced by Ang II. Chromatin immunoprecipitation PCR confirmed that FoxM1 bound to Wnt1, Wnt2b, Wnt3 promoters and luciferase assay further identified that the transcriptions of Wnt1, Wnt2b and Wnt3 were regulated by FoxM1. Thus, our findings show that multi‐Wnt family members were regulated by transcriptional factor FoxM1. FoxM1 might be a key switch for activating β‐catenin pathway and renal fibrosis. Therefore, FoxM1 might be a potential therapeutic target in manipulating renal fibrosis.

Thiol-functionalized degradable polyesters have significant applications in nanoscience and polymer chemistry due to the combination of the biodegradability and biocompatibility of polyesters and the special chemical and physical properties of thiols. It is challenging to synthesize thiol-functionalized polyesters via ring-opening polymerization by using unprotected mercapto-alcohol as an initiator because both hydroxyl and thiol have the ability to initiate the polymerization. Since 2005, the protecting-group-free synthetic strategy has been reported based on chemoselective catalysis and microflow technology. In this review, non-metal and metal catalytic unprotected mercapto-alcohol initiating ring-opening polymerization is summarized in order. The advantages of using flow chemistry are highlighted. The remaining challenges and opportunities are discussed for the development of thiol-polymer synthesis and applications.

BACKGROUND: Sepsis has always been a challenge in pediatric intensive care unit (PICU) with poor prognosis. In order to evaluate the effect between routine continuous renal replacement therapy (CRRT) and high-volume hemofiltration (HVHF) in children with sepsis, we performed out this prospective, randomized, controlled, open-label trial. METHODS: Forty-seven children with sepsis were enrolled from January 2015 to December 2016. Twenty-two patients in Control group received routine CRRT and 25 patients in HVHF group received HVHF within 6 hours after the diagnosis of sepsis. The oxygenation index, serum creatinine, urea, lactate, inflammatory cytokines (IL-6, IL-10, and TNF-α), pediatric risk of mortality III (PRISM III) and 28-day mortality rate were collected and compared. RESULTS: The oxygenation index in HVHF group and Control group was significantly increased at 48 hours (P0.05). CONCLUSIONS: HVHF might be an effective treatment for children with sepsis.

In this paper, a series of Li3V2(PO4)3/C composite nanofibers is prepared by a facile and environmentally friendly electrospinning method and calcined under different temperatures. The LVP nanofiber calcined under 900 ℃ exhibits the best electrochemical performance. The bicontinuous morphologies of LVP/CNF are the fibers shrunk and the LVP crystals simultaneously grown. At the range of 3.0–4.3 V, LVP/CNF obtained under 900 ℃ delivers the initial capacity of 135 mAh/g, close to the theoretical capacity of LVP. Even at high current density, the sample of LVP/CNF still presents good electrochemical performance.

Although T cell centered immune checkpoint blockade (ICB) therapies have shown unprecedented success in various cancer types, only a minority of patients benefit from these treatments due to the lack of neoantigen burden and exhaustion of tumor-infiltrating immune stimulating cells. Inspired by the crucial role of NK cell based immunity and potential immunostimulating effect of chemotherapeutic drugs, the therapeutic efficiency on tumor inhibition through combination of doxorubicin (DOX) and blockade of TIGIT (T-cell Ig and ITIM domain), a co-inhibitory receptor expressed by both NK and T cells, in a matrix metalloproteinase 2 (MMP-2)-degradable hydrogel was thoroughly evaluated in this study. Due to the distinct release kinetics from destructed framework of hydrogels, the differentially released DOX and anti-TIGIT monoclonal antibody (aTIGIT) molecules could elicit immunogenic tumor microenvironment and reverse the exhaustion of NK and effector T cells to realize not only durable localized tumor inhibition but also systemic and long-lasting immune memory responses. Thus, our work pioneered the union of chemotherapeutic drugs and NK cell centered ICB therapies for activating cascade-like anti-tumor immune responses through eliciting immunogenic tumor microenvironment and boosting both innate and adaptive immunity. This article is protected by copyright. All rights reserved.

Rheumatoid arthritis (RA) is a chronic, progressive and systemic autoimmune disease mainly characterized by symmetric multijoint synovitis. Quercetin has anti-inflammatory, anti-oxidation and immune regulation activities, and therefore shows high medicinal value. The present study aimed to observe the effect of quercetin on fibroblast-like synoviocytes (FLSs) in RA. Rheumatoid arthritis fibroblast-like synoviocytes (RAFLSs) were pretreated with 50 nmol/l quercetin for 2 h and were then stimulated using TNF-α for 24 h for subsequent experiments. RAFLSs were transfected with short interfering (si)-X-inactive specific transcript (XIST), microRNA (miR)-485 mimic, miR-485 inhibitor or si-PSMB8 or combination. ELISA, PCR and western blotting was used to evaluate the effect of quercetin on RAFLSs treated with TNF-α. It was revealed that quercetin inhibited the production of inflammatory cytokines and the expression of XIST in RAFLSs induced by TNF-α. Bioinformatics analysis indicated that XIST acted as a sponge for miR-485 and that proteasome subunit β type-8 (PSMB8) was a direct target of miR-485. Moreover, PSMB8 functioned as a suppressor in inflammatory cytokine production of RAFLSs induced by TNF-α. Overall, quercetin was observed to inhibit the production of inflammatory cytokines and the expression of XIST in RAFLSs induced by TNF-α. Moreover, XIST-silencing could suppress the inflammatory reaction by sponging miR-485 in cells treated with TNF-α. Altogether, quercetin could suppress the development of RA in vitro.

Cordyceps militaris is a well-known traditional Chinese medicine. Studies have demonstrated that the polysaccharides of C. militaris have various bioactivities. However, their mechanisms of action remain unclear. We previously purified a water-soluble polysaccharide CM1 from C. militaris and found that it has a cholesterol efflux improving capacity. This study further investigates the effect of CM1 in anti-atherosclerosis and its underlying mechanism in apolipoprotein E-deficient mice. Our data indicated that CM1 significantly decreased the total cholesterol and triglyceride in the plasma of mice, and decreased lipid deposition and formation of atherosclerotic plaque in a dose-dependent manner. Integrated bioinformatics analysis revealed that CM1 interacted with multiple signaling pathways, including those involved in lipid metabolism, inflammatory response, oxidoreductase activity and fluid shear stress, to exert its anti-atherosclerotic effect. Molecular technology analysis showed that CM1 enhanced the expression of proteins involved in lipid metabolism, reduced the expression of intercellular adhesion molecule-1 and tumor necrosis factor-α in the aorta, and decreased the content of oxidative products by enhancing the activities of antioxidant enzymes. Microarray analysis and biochemical data indicated that CM1 can improve lipid metabolism, reduce inflammation and oxidative stress. Taken together, CM1 could be used for the treatment of hyperlipidemia and atherosclerotic cardiovascular diseases.

Helicid is a specific Chinese natural drug. Helicid, its congeners, and its derivatives exhibit pronounced biological activities, among which its hypnotic effects stand out. The well-documented sedation and analgesic activity and low side effects of helicid have drawn more and more attention from scientists. Moreover, its clinical success and intriguing mechanism of action have stimulated great interest in further modification of helicid for improving its hypnotic activity. The 4-formyl group has been a major target for structural derivatization aimed at either producing more potent compounds or overcoming drug disadvantages. Accordingly, numerous helicid derivatives have been prepared via molecular docking and hemisynthesis. Although neither systematic nor comprehensive, there are two excellent reviews on the distribution, sources, applications, synthesis, and pharmacological activity of helicid that have been published in Chinese. In the present review, we attempt to compile and discuss the key data available in the literature on the multiple biological activities of helicid derivatives. This compilation of 102 references may be helpful in understanding the diverse biological properties of helicid while providing insights into its mechanism of action. This may direct future research in the synthesis of new derivatives and the exploration of other biological activities.

The equilibrium solubility of amidinothiourea (ATU) in monosolvents, including N-methyl-2-pyrrolidone (NMP), acetone, 1,4-dioxane, acetonitrile, ethyl acetate, toluene, methanol, 1-butanol, 1-propanol, ethanol, 2-propanol, and cyclohexane, was determined by using a isothermal saturation method. The experimental temperature and pressure are 283.15–323.15 K and 101.3 kPa, respectively. The sequence of solubility from high to low is NMP > acetone > 1,4-dioxane > methanol > ethanol > acetonitrile > 1-propanol > ethyl acetate > 2-propanol > 1-butanol > toluene > cyclohexane. Two models (modified Apelblat equation and λh equation) were employed to describe the relationships between solubility of ATU in mole fraction and temperature, and the values of relative average deviations and root-mean-square deviations between the experimental and calculated solubilities were no more than 2.07% and 1.96×10–4, respectively. The appropriateness of the models was evaluated by statistical analysis. Based on the results of st...

Lipid metabolism that correlates tightly to the glucose metabolic regulation in malignant cells includes hepatocellular carcinoma (HCC) cells. The transcription factor Sterol Regulatory Element Binding Protein 1 (SREBP-1), a regulator of fatty acid synthesis, has been shown to pivotally regulate the proliferation and metastasis of HCC cells. However, the intrinsic mechanism by which SREBP-1 regulates the survival of HCC cells remains unclear. In this study, among HCC patients who had dismal responses to Sorafenib, a high SREBP-1 level was found in the tumors and correlated to poor survival. This observation suggested the negative role of SREBP-1 in clinical HCC prognosis. Our mechanistical studies reveal that the inhibition of SREBP-1 via its inhibitor Betulin suppresses cellular glucose metabolism. In addition to the reduced glycolytic activity, a thwarted metastatic potential was observed in HCC cells upon Betulin administration. Moreover, our data show that SREBP-1 inhibition facilitated the antitumor effects of Sorafenib on HCC cells and xenograft tumors.

In this research, the solid–liquid equilibrium solubility of diclazuril was measured by the isothermal saturation method, and the influence of the solvent effect on solubility was discussed. In monosolvents, at the determined temperature, the solubility values of diclazuril decrease according to the order: dimethylformamide (DMF) > acetone > acetonitrile > ethyl acetate > methanol > ethanol > 1-propanol > 2-propanol > 1-butanol > toluene. Besides, in two binary solvent mixtures, the solubility increases with the increasing ratio of DMF/acetone and decreases with the increase of ethanol. What is more, five models including modified Apelblat equation, λh equation, Jouyban–Acree model, van’t Hoff–Jouyban–Acree model, and Apelblat–Jouyban–Acree model were used to correlate the diclazuril solubility in monosolvents and binary solvent mixture systems. The relative average deviation and root-mean-square deviation values were no more than 0.97% and 6.95 × 10–4, respectively. All these five models can correlate th...

As a water-soluble polymer, the widely used polyvinyl alcohol (PVA) is produced from hydrolysis of polyvinyl acetate. Microbial PVA carbon backbone cleavage via a two-step reaction of dehydrogenation and hydrolysis has been well studied. Content of acetyl group is a pivotal factor affecting performance of PVA derivatives in industrial application, and deacetylation is a non-negligible part in PVA degradation. However, the genetic and biochemical studies of its deacetylation remain largely elusive. Here, Comamonas sp. strain NyZ500 was isolated for its capability of growing on acetylated PVA from activated sludge. A spontaneous PVA-utilization deficient mutant strain NyZ501 was obtained when strain NyZ500 was cultured in rich media. Comparative analysis between the genomes of these two strains revealed a fragment (containing a putative hydrolase gene dacApva ) deletion in NyZ501 and dacApva-complemented strain NyZ501 restored the ability to grow on PVA. DacApva, which shares 21% identity with xylan esterase AxeA1 from Prevotella ruminicola 23, is a unique deacetylase catalyzing the conversion of acetylated PVA and its derivatives to deacetylated counterparts. This indicates that strain NyZ500 utilizes acetylated PVA via acetate as a carbon source to grow. DacApva also possessed the deacetylation ability for acetylated xylan and the antibiotic intermediate 7-aminocephalosporanic acid (7ACA) but the enzymes for the above two compounds had no activities against PVA derivatives. This study enhanced our understanding of the diversity of microbial degradation of PVA and DacApva characterized here is also a potential biocatalyst for the eco-friendly biotransformation of PVA derivatives and other acetylated compounds.IMPORTANCE: Water-soluble PVA, which possesses a very robust ability to accumulate in the environment, has a very grave environmental impact due to its widespread use in industrial and household applications. On the other hand, chemical transformation of PVA derivatives is currently being carried out at high energy consumption and high pollution conditions using hazardous chemicals (such as NaOH, methanol) under high temperatures. The DacApva reported here performs PVA deacetylation under mild conditions, then it has a great potential to be developed into an eco-friendly biocatalyst for biotransformation of PVA derivatives. DacApva also has deacetylation activity for compounds other than PVA derivatives, which facilitates its development into a broad-spectrum deacetylation biocatalyst for production of certain desired compounds.

The left-right symmetry breaking of vertebrate embryos requires fluid flow (called nodal flow in zebrafish). However, the molecular mechanisms that mediate the asymmetric gene expression regulation under nodal flow remain elusive. In this paper, we report that heat shock factor 1 (HSF1) is asymmetrically activated in the Kuppfer’s vesicle at the early stage of zebrafish embryos in the presence of nodal flow. Deficiency in HSF1 expression caused a significantsitus inversusand disrupted gene expression asymmetry of nodal signaling proteins in zebrafish embryos. Further studies demonstrated that HSF1 could be immediately activated by fluid shear stress. The mechanical sensation ability of HSF1 is conserved in a variety of mechanical stimuli in different cell types. Moreover, cilia and the Ca2+-Akt signaling axis are essential for the activation of HSF1 under mechanical stressin vitroandin vivo. Considering the conserved expression of HSF1 in organisms, these findings unveil a fundamental mechanism of gene expression regulation triggered by mechanical clues during embryonic development and other physiological and pathological transformations.

The problem of antimicrobial resistance (AMR) is becoming increasingly serious. Bacteria producing extended spectrum beta-lactamase (ESBL), which can hydrolyze beta-lactam antibiotics, are among the most important drug resistant bacteria. Rapid AMR analysis methods are essential for identifying antibiotic resistant bacteria, which is of significant positive value to the clinical therapy of infectious disease. We developed a platform which integrates a sandwich microfluidic filter device with electrospray ionization mass spectrometry (ESI-MS). Bacterial cells were loaded in the sandwich microfluidic chip and antibiotic drugs were injected to pass through the blocked bacterial cells. By online ESI-MS analysis of the antibiotic drugs and their hydrolysis products, the AMR of the bacteria can be assessed within 30 minutes. Four Escherichia coli strains, namely two ESBL-positive and two ESBL-negative, were successfully discriminated using ampicillin and the third generation cephalosporin ceftriaxone. Considering the simplicity and high efficiency of the assay, the microfluidic chip integrated online ESI-MS system is promising in the rapid clinical diagnosis of ESBL-producing bacteria.

Ectopic adenosine triphosphate (eATP) synthase, located on the cell surface instead of the mitochondrial inner membrane, has been discovered to be a novel target for the treatment of various types of cancer. However, the mechanism of eATP synthase trafficking toward the cell surface remains unclear. In this study, we used an integrative approach incorporating multiomics, super-resolution imaging, real-time live-cell tracing, and various functional analyses to derive a transport model of eATP synthase from the mitochondria to the plasma membrane in cancer cells. We determined that the ATP synthase complex is first assembled in the mitochondria and subsequently delivered to the cell surface through the microtubule-mediated mitochondrial transport pathway. We also found that dynamin-related protein 1 (DRP1) enhances mitochondrial fission and subsequently associates with microtubule motor protein kinesin family member 5B (KIF5B) to promote the subcellular transportation of eATP synthase. Consequently, our work provides a blueprint for eATP synthase trafficking from the mitochondria toward the cell surface.

A fluorescent aptasensor for Staphylococcus aureus (S. aureus) is designed, which takes advantage of strand displacement amplification (SDA) technology and unique self-assembled DNA hexagonal structure. In the presence of S. aureus, a partially complementary strand of S. aureus aptamer (cDNA) is competitively released from cDNA/aptamer duplex immobilized on magnetic beads due to the affinity of the aptamer for S. aureus. The addition of primer starts the SDA reaction. With the catalysis of Bsm DNA polymerase and Nb.bpu10I endonuclease, a large number of single-stranded DNA (ssDNA) is produced, which induces the opening of a hairpin probe and the subsequent self-assembly to form a hexagonal structure. The staining of the DNA hexagon with SYBR Green I excites the fluorescence signal, which is used for detection. The aptasensor exhibits a broad linear range from 7 to 7 × 107 CFU/mL, with a detection limit of 1.7 CFU/mL for S. aureus. The sensor shows negligible responses to other bacteria. Moreover, the aptasensor has been applied to detect S. aureus in milk samples, and the results demonstrate the general applicability of the sensor and its prospect in systematic detection of S. aureus in food safety control and medicine-related fields.

Zhuo-Yue Li,1,2 Yi-Fan Yin,1,2 Yang Guo,1,2 Hui Li,1,2 Mei-Qi Xu,1,2 Man Liu,1,2 Jing-Ru Wang,1,2 Zhen-Han Feng,1,2 Xiao-Chuan Duan,1,2 Shuang Zhang,1,2 Shuai-Qiang Zhang,1,2 Guang-Xue Wang,2 Ai Liao,2 Shu-Min Wang,3 Xuan Zhang1,2 1Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing 100191, People’s Republic of China; 2Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100191, People’s Republic of China; 3Department of Ultrasound, Peking University Third Hospital, Peking University, Beijing 100191, People’s Republic of ChinaCorrespondence: Xuan ZhangDepartment of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Xueyuan Road 38, Beijing 100191, People’s Republic of ChinaTel/Fax +86-10-82805765Email xuanzhang@bjmu.edu.cnShu-Min WangDepartment of Ultrasound, Peking University Third Hospital, Peking University, Xueyuan Road 38, Beijing 100191, People’s Republic of ChinaEmail shuminwang2014@163.comIntroduction: Because tumor-associated inflammation is a hallmark of cancer treatment, in the present study, sorafenib mesoporous silica nanomatrix (MSNM@SFN) co-administrated with flufenamic acid (FFA, a non-steroidal anti–inflammatory drug (NSAID)) was investigated to enhance the anti-tumor activity of MSNM@SFN.Methods: Metastatic breast tumor 4T1/luc cells and hepatocellular carcinoma HepG2 cells were selected as cell models. The effects of FFA in vitro on cell migration, PGE2 secretion, and AKR1C1 and AKR1C3 levels in 4T1/luc and HepG2 cells were investigated. The in vivo anti-tumor activity of MSNM@SFN co-administrating with FFA (MSNM@SFN+FFA) was evaluated in a 4T1/luc metastatic tumor model, HepG2 tumor-bearing nude mice model, and HepG2 orthotopic tumor-bearing nude mice model, respectively.Results: The results indicated that FFA could markedly decrease cell migration, PGE2 secretion, and AKR1C1 and AKR1C3 levels in both 4T1/luc and HepG2 cells. The enhanced anti-tumor activity of MSNM@SFN+FFA compared with that of MSNM@SFN was confirmed in the 4T1/luc metastatic tumor model, HepG2 tumor-bearing nude mice model, and HepG2 orthotopic tumor-bearing nude mice model in vivo, respectively.Discussion: MSNM@SFN co-administrating with FFA (MSNM@SFN+FFA) developed in this study is an alternative strategy for improving the therapeutic efficacy of MSNM@SFN via co-administration with NSAIDs.Keywords: sorafenib mesoporous silica nanomatrix, MSNM@SFN, flufenamic acid, FFA, PGE2, AKR1C1, AKR1C3, 4T1/luc, HepG2

Gastric cancer is one of the most common types of cancer worldwide. Nevertheless, effective therapeutic strategies have not yet been discovered. Several studies have shown that tanshinone IIA (TIIA), which is extracted from the traditional herbal medicine plant Danshen (Salvia miltiorrhiza), has potential activity against many kinds of cancer. Our previous research demonstrated that TIIA can induce cell death in gastric cancer. However, the exact signaling pathway response is still unclear. Post-translational modification (PTM) plays a significant role in a wide range of physiological processes in cancer, via regulation of both signal transduction cascades and many cellular pathways. Here, we integrated multilayer omics-transcriptomics and dynamic phosphoproteomics-to elucidate the regulatory networks triggered by TIIA in gastric cancer. We identified the phosphorylation of heat shock protein 27 (HSP27) at serine 82 in response to TIIA, which caused reactive oxygen species (ROS) production and unfolded protein response (UPR). Moreover, the accumulation of cellular stress increased the expression of heat shock factor 1 (HSF1). In addition, the downstream targets of HSF1, which were involved in heat shock stress and apoptosis, were also activated in TIIA-treated cells. In conclusion, this study performs a multiomic approach to clarify a comprehensive TIIA-responsive network leading to cell death in gastric cancer.

Static light scattering is a popular physical chemistry technique that enables calculation of physical attributes such as the radius of gyration and the second virial coefficient for a macromolecule (e.g., a polymer or a protein) in solution. The second virial coefficient is a physical quantity that characterizes the magnitude and sign of pairwise interactions between particles, and hence is related to aggregation propensity, a property of considerable scientific and practical interest. Estimating the second virial coefficient from experimental data is challenging due both to the degree of precision required and the complexity of the error structure involved. In contrast to conventional approaches based on heuristic ordinary least squares estimates, Bayesian inference for the second virial coefficient allows explicit modeling of error processes, incorporation of prior information, and the ability to directly test competing physical models. Here, we introduce a fully Bayesian model for static light scattering experiments on small-particle systems, with joint inference for concentration, index of refraction, oligomer size, and the second virial coefficient. We apply our proposed model to study the aggregation behavior of hen egg-white lysozyme and human γS-crystallin using in-house experimental data. Based on these observations, we also perform a simulation study on the primary drivers of uncertainty in this family of experiments, showing in particular the potential for improved monitoring and control of concentration to aid inference.

The basis of purification and further theoretical studies of 2-amino-4,6-dichoropyrimidine is the solubility and solution thermodynamics in different solvents. In this paper, the solubility of 2-amino-4,6-dichoropyrimidine in 10 neat solvents (methanol, ethanol, n-propanol, isopropanol, acetone, acetonitrile, ethyl acetate, 1,4-dioxane, toluene, and cyclohexane) and binary liquid mixtures (ethyl acetate + ethanol) was measured by the isothermal saturation method at temperatures range from 278.15 to 318.15 K, at p = 101.2 kPa. High-performance liquid chromatography (HPLC) was used to analyze the solubility of 2-amino-4,6-dichoropyrimidine in selected solvents. To sum up, the equilibrium mole fraction solubility was highest in 1,4-dioxane (2.619 × 10–2 at 318.15 K) and lowest in cyclohexane (0.02238 × 10–2 at 318.15 K), and ranked as 1,4-dioxane (2.619 × 10–2 at 318.15 K) > acetone (1.630 × 10–2 at 318.15 K) > ethyl acetate (1.471 × 10–2 at 318.15 K) > acetonitrile (0.5048 × 10–2 at 318.15 K) > methanol (0....

BACKGROUND Osteosarcoma is the most common primary bone malignancy and often presents at an early age. Calycosin is a phytoestrogen isoflavone, which has previously been reported to inhibit tumor cell growth. The aim of this study was to investigate the effects of calycosin on apoptosis of estrogen receptor (ER)-positive and ER-negative human osteosarcoma cell lines and tumor xenografts in mice. MATERIAL AND METHODS Cultured ER-positive MG-63 human osteosarcoma cells and ER-negative U2-OS human osteosarcoma cells were treated with increasing doses of calycosin (0, 25, 50, and 100 μm). Cell viability and apoptosis were studied by an MTT assay and flow cytometry. Western blot measured the expression levels of the apoptosis-related protein p-PI3K, p-Akt, and p-mTOR in MG-63 cells, with and without pretreatment with the PI3K inhibitor, LY294002, the AKT inhibitor, MK-2206, or the mTOR inhibitor, rapamycin. MG-63 tumor-bearing nude mice were used to evaluate the effects of treatment with calycosin. RESULTS Calycosin treatment inhibited proliferation and induced apoptosis in MG-63 cells, but had no effect on U2-0S cells. In MG-63 cells, calycosin treatment increased the expression of the PI3K/AKT/mTOR pathway proteins; inhibitor assays showed that expression of the PI3K protein was most strongly associated with the antitumor effects of calycosin. In the nude mouse MG-63 tumor xenografts, calycosin inhibited tumor growth and regulated the expression levels of apoptosis-related PI3K/AKT/mTOR pathway proteins. CONCLUSIONS The phytoestrogen, calycosin, induced apoptosis of cells of the ER-positive osteosarcoma cell line, MG-63, via the PI3K/AKT/mTOR pathway, with these effects being mainly due to PI3K.

The hybrids of metal-based materials supported by carbon nanofibers (CNFs) have potential application in reversible energy storage devices. In this work, four kinds of CoCO3 micrometer particles stabilized in the network of CNFs are designed and synthesized by using solvothermal method. The composite electrodes of cubic-CoCO3/CNF, spherical-CoCO3/CNF, spindle-CoCO3/CNF and dumbbell-CoCO3/CNF deliver the initial specific capacities of 1190, 987, 1193 and 1108 mAh g−1, respectively, and remain 503, 584, 666, 551 mAh g−1 at the 100th cycle. Bare spindle CoCO3 delivers the highest capacity of 1588 mAh g−1, but CoCO3 without the support of CNFs only remains 140 mAh g−1 at the 100th cycle. Spindle-CoCO3/CNF composite electrode exhibits the best rate performance, delivering 507 mAh g−1 at the current density of 1.0 A g−1. The ex-situ field emission scanning electron microscope (FESEM) images show that CNFs elastically buffer the volume change of CoCO3 during lithiation/delithiation cycles. CNFs as substrate play the important roles in providing excellent conductive channel to improve the rate capability and effective matrix buffering the volume change to promote the cyclic performance. This work presents a scalable approach to synthesize and optimize the hybrid structure of CoCO3/CNF for potential application in highly reversible lithium storage devices.

Xiu-Chai Zheng,1,2,* Wei Ren,1,2,* Shuang Zhang,1,2 Ting Zhong,1,2 Xiao-Chuan Duan,1,2 Yi-Fan Yin,1,2 Mei-Qi Xu,1,2 Yan-Li Hao,1,2 Zhan-Tao Li,1,2 Hui Li,1,2 Man Liu,1,2 Zhuo-Yue Li,1,2 Xuan Zhang1,2 1Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing, People’s Republic of China; 2Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing, People’s Republic of China *These authors contributed equally to this work Background: In the present study, the tumor-specific, pH-responsive peptide H7K(R2)2 -modified, theranostic liposome-containing paclitaxel (PTX) and superparamagnetic iron oxide nanoparticles (SPIO NPs), PTX/SPIO-SSL-H7K(R2)2, was prepared by using H7K(R2)2 as the targeting ligand, SPIO NPs as the magnetic resonance imaging (MRI) agent, PTX as antitumor drug. Methods: The PTX/SPIO-SSL-H7K(R2)2 was prepared by a thin film hydration method. The characteristics of PTX/SPIO-SSL-H7K(R2)2 were evaluated. The targeting effect, MRI, and antitumor activity of PTX/SPIO-SSL-H7K(R2)2 were investigated detail in vitro and in vivo in human breast carcinoma MDA-MB-231 cell models. Results: Our results of in vitro flow cytometry, in vivo imaging, and in vivo MR imaging confirmed the pH-responsive characteristic of H7K(R2)2 in MDA-MB-231 cell line in vitro and invivo. The results of in vivo MRI and in vivo antitumor activity confirmed the theranostic effect of PTX/SPIO-SSL-H7K(R2)2 in MDA-MB-231 tumor-bearing model. Conclusion: Considering all our in vitro and in vivo results, we conclude that we developed targeting modified theranostic liposome which could achieve both role of antitumor and MRI. Keywords: tumor-specific pH-responsive peptide, paclitaxel, superparamagnetic iron oxide nanoparticles, liposome, theranostic efficiency

Spinel LiMn 2 O 4 has drawn continuous attentions due to its low cost, good electrochemical performance, environmental friendliness and natural abundant resources. In view of its severe capacity fading, some types of manganese-based compounds with different Mn oxidation states are selected to protect bare LiMn 2 O 4 by constructing a stable coating layer. In this work, LiMn 2 O 4 @LiMnPO 4 composite, spherical LiMn 2 O 4 (LMO) as core and Mn 2+ -rich phase of LiMnPO 4 (LMP) as shell, is designed and synthesized. Two composites of LiMn 2 O 4 particles coated with 3 wt% and 10 wt% LiMnPO 4 have been compared studied. After 100 cycles at 0.5C rate, the two samples deliver capacity retentions of 96.63% and 93.23% of their initial capacities. Moreover, LMO coated by 3 wt% LiMnPO 4 delivers 100.3 mAh g −1 after 200 cycles at 10C rate and 76.3 mAh g −1 after 1000 cycles at 20C rate, much higher than bare LiMn 2 O 4 with 90 mAh g −1 and 45.8 mAh g −1 , respectively. This core-shell structure with Mn 2+ -rich phase as a coating layer effectively enhance the material’s cycling performance and rate capacity by reducing the contact of LiMn 2 O 4 with electrolyte.

Bisphenol-A polycarbonate (PC) is a widely used engineering thermoplastic and its release has caused damage to the ecosystem. Microbial degradation of plastic represents a sustainable approach for PC reduction. In this study, a bacterial strain designated Pseudoxanthomonas sp. strain NyZ600 capable of degrading PC was isolated from activated sludge by using diphenyl carbonate as a surrogate substrate. Within a 30-day period of incubating with strain NyZ600, PC films were analyzed with atomic force microscopy, scanning electron microscope, water contact angle, X-ray photoelectron spectroscopy, fourier transform infrared spectroscopy, differential scan calorimeter and thermogravimetric analysis technique. The analyses results indicated that the treated PC films were bio-deteriorated and formed some “corrosion pits” on the PC film surface. In addition, strain NyZ600 performed broad depolymerization of PC indicated by the reduction of Mn from 23.55 to 16.75 kDa and Mw from 45.67 to 31.97 kDa and two degradation products bisphenol A and 4-cumylphenol (the two monomers of PC) were also found, which established that PC were biodegraded by strain NyZ600. Combing all above results, it is clear that the strain NyZ600 can degrade PC which provides a unique example for bacterial degradation of PC and a feasibility for the removal of PC waste.

Triple-negative breast cancer (TNBC) shares the molecular features facilitating epithelial-to-mesenchymal transition (EMT), which contributed to tumor invasion and metastasis. A platinum(IV) conjugate ketoplatin deriving from FDA-approved drugs cisplatin and ketoprofen was designed and prepared to enhance antitumor activity and suppress EMT in TNBC via positive impact on inflammatory microenvironment by modulating COX-2 signal. As a prodrug, ketoplatin afforded 50.26-fold higher cytotoxicity than cisplatin against TNBC mesenchymal-stem cell-like MDA-MB-231 cells, partly attributing to its dramatic increase of cellular uptake and DNA damage. More importantly, EMT progress in MDA-MB-231 was markedly restrained by ketoplatin, resulting from the suppression of vimentin and N-cadherin mediated by down-regulated COX-2. Further in vivo investigation exhibited that ketoplatin effectively inhibited tumor growth and reduced systemic toxicity compared to cisplatin. Overall, ketoplatin possessed high antitumor activity and low toxicity against TNBC MDA-MB-231 in vitro and in vivo.

Spinel LiMn2O4 is one of the most important cathode materials but it still suffers from rapid capacity degradation during electrochemical cycling. Beside surface coating to improve the electrochemical performances, controlling the bulk morphology of LiMn2O4 (LMO) is another effective strategy. In this work, porous LiMn2O4 microspheres composed of numerous primary nanoparticles are synthesized by micro-emulsion and co-precipitation methods. The porous structure and the primary nanoparticles size of LiMn2O4 are effected by the concentration of micro-emulsion and the precursor of Mn2+. The well-established porous LiMn2O4 microspheres with abundant ionic channels and good contact with electrolyte endow the spinel a remarkable electrochemical performance. After 300 cycles, 0.50M-LMO sample presents excellent reversible capacity of 112.8 mAh g-1 at 0.5 C rate. After 1000 cycles, 0.50M-LMO sample presents the highest capacity of 97.9 mAh g-1 and remains 54.2 mAh g-1 at the current rate of 10 C. The porous spherical structure of cathode materials is essential to improve the rate performance due to the good contact between the active material and electrolyte.

Spinel LiNi0.5Mn1.5O4 (LNM) is a potential high-voltage cathode for commercial lithium-ion batteries (LIBs). Maintaining an appropriate amount of Mn3+ in LNM is necessary to improve the rate performance. However, Mn3+ dissolution in the interface of LNM and electrolyte leads to the fast capacity degradation. Therefore, designing a cathode to prevent Mn3+ loss during charge/discharge is important for high performance LIBs. Here we present an active core-shell design with coating another high-voltage cathode material LiCoPO4 (LCP) on the surface of LNM nanoparticles. The LCP layer can simultaneously induce Mn3+ ions at the interface between LCP and LNM, and act as a stable shell to prevent the loss of Mn3+. The optimized sample LNM@5%LCP possesses 128 mAh g−1 at 0.5 C and 115 mAh g−1 at 20 C rate, and maintains 96% of the initial capacity operated at 55 °C over 100 cycles.

Urea as a cheap reagent is very useful in preparation two-dimensional metal oxides with tunable crystal morphologies, while refluxing method is a simple route to control the decomposition of urea. Here, a low temperature refluxing in the presence of urea is developed to prepare porous Co3O4 as anode material for lithium-ion batteries. The self-assembly cobalt hydrotalcite-like compounds (Co-HLC) is firstly synthesized through refluxing the mixture of cobaltous nitrate and urea. After pyrolysis, the flower-like morphology of Co-HLC is successfully maintained in the final product of Co3O4. The ordered two-dimensional Co3O4 nanosheets provide good contact with electrolyte and stable porous structure during lithiation/delithiation. Co3O4-120 synthesized under refluxing temperature of 120 °C shows the initial charge capacities of 722 and 741 mAh g−1 at the 2nd and 100th cycle under 100 mA g−1. Moreover, Co3O4-120 as electrode for a supercapacitor presents excellent capacitance, 167 F g−1 after 3000 cycles at 1 A g−1. Under 5, 10 and 20 A g−1, Co3O4-120 electrode delivers 128, 104 and 90 F g−1, respectively. The porous structure in Co3O4 with enhanced electrochemical performance indicates low temperature refluxing preparation is an applicable and energy-saved method to synthesize transitional metal oxide with tunable crystal morphologies.

In the present study, we select the Sylysia 350 (Sylysia) as mesoporous material, distearoylphosphatidylethanolamine-poly(ethylene glycol)2000 (DSPE-PEG) as absorption enhancer and hydroxy propyl methyl cellulose (HPMC) as crystallization inhibitor to prepare sorafenib tosylate (SFN) nanomitrix (MSNM@SFN) for improving the anti-tumor activity of SFN. The MSNM@SFN was prepared by solvent evaporation method. The solubility, dissolution, and bioavailability of SFN in MSNM@SFN were also investigated. The anti-tumor activity of MSNM@SFN was evaluated in vitro and in vivo. Our results indicated that the solubility and dissolution of SFN in MSNM@SFN were significantly increased. The oral bioavailability of SFN in MSNM@SFN was greatly improved 7.7-fold compared with that in SFN suspension. The enhanced anti-tumor activity of MSNM@SFN was confirmed in vitro and in vivo experiments. This nanomatrix developed in this study could be a promising drug delivery platform for improving the therapeutic efficacy of poorly water-soluble drugs.

Li-rich manganese based cathode material is important in lithium-ion batteries that has received major research attention because of its high specific capacity (more than 250 mAh g −1 ). This work investigates the impact of self-propagating synthesis (SHS) and characterization of Li 1.2± x Ni 0.13± x Co 0.13± x Mn 0.53± x O 2 ( x = 0, 0.3). Li 1.2 Ni 0.13 Co 0.13 Mn 0.53 O 2 delivers the initial capacity of 260.8 mAh g −1 at the current rate of 0.1C. The initial capacity loss is attributed to the electrochemical activation of Li 2 MnO 3 which results in the stabilization of the host structure of Li 1.2± x Ni 0.13± x Co 0.13± x Mn 0.53± x O 2 ( x = 0, 0.3) in the following cycles. After 100 cycles, the sample with highest content of Li 2 MnO 3 can remain 84% of the initial capacity. Li 2 MnO 3 component is mainly helpful the stabilization of crystal structure and improvement of capacity, but is negative to the lithium diffusion ability reflected in the poor rate performance. The sample with optimized content of Li 2 MnO 3 delivers the best electrochemical properties.

A fluorescent detection of Staphylococcus aureus (S. aureus) is established based on a finely designed functional chimera sequence, a molecular beacon (MB), and strand displacement target recycling. The chimera sequence, which consists of the aptamer sequence of S. aureus and the complementary sequence of MB, can form a hairpin structure due to the existence of intramolecular complementary regions. When S. aureus is present, it binds to the aptamer region of the chimera, opens the hairpin and unlocks the complementary sequence of MB. Subsequently, the MB is opened and intensive fluorescence signal is restored. To increase the sensitivity of the detection, signal amplification is achieved through strand displacement-based target recycling. With the catalysis of Nb. Bpu10I nicking endonuclease and Bsm DNA polymerase, the MB sequence can be cleaved and then elongated to form a complete duplex with the chimera, during which S. aureus is displaced from the chimera and proceeded to the next round of the reaction. This assay displays a linear correlation between the fluorescence intensity and the logarithm of the concentration of S. aureus within a broad concentration range from 80 CFU/mL to 8 × 106 CFU/mL. The detection limit of 39 CFU/mL can be derived. The assay was applied to detect S. aureus in different water samples, and satisfactory recovery and repeatability were achieved. Hence the designed chimera sequence and established assay have potential application in environmental pollution monitoring.

(d)-Glucosamine and other nutritional supplements have emerged as safe alternative therapies for osteoarthritis, a chronic and degenerative articular joint disease. N-acetyl-(d)-glucosamine, a compound that can be modified at the N position, is considered to improve the oral bioavailability of (d)-glucosamine and has been proven to possess greater in vitro chondroprotective activity compared with the parent agent. In this study, to further utilize these properties, we focus on the modification of the N position with a benzenesulfonyl and different isoxazole formyl groups. Among these compounds, the 3-(2-chlorobenzene)-5-methyl-isoxazole formyl chloride and p-methoxybenzenesulfonyl chloride modifying structures proved to be the most active of the series and efficiently processed the chondrocytes in vitro. These novel N-position substitution compounds may represent promising leads for osteoarthritis drug development.

Hypoxia is an important microenvironmental pressure present in the majority of solid tumors and, so, tumor hypoxia might be considered an attractive target for tumor therapy. One strategy for targeting hypoxia is to develop bioreductive prodrugs. In the present research, we synthesized a bioreductive paclitaxel prodrug, 3-(2-Nitrophenyl) propionic acid-paclitaxel (NPPA-PTX). The stability of NPPA-PTX in PBS and rat plasma was investigated. The anti-tumor activity of NPPA-PTX was also evaluated in vitro and in vivo. The results of our stability study indicated that NPPA-PTX was stable in PBS and rat plasma as well as in the blood circulation. The in vitro and in vivo anti-tumor activity of NPPA-PTX was confirmed in both KB cells and MDA-MB-231 cells. Our results also indicated that NPPA-PTX could completely convert to active PTX in tumor tissues and produced the anti-tumor activity in both KB and MDA-MB-231 tumor-bearing nude mice. We suggest that the dissociated PTX which converted from NPPA-PTX in tumor tissues played a key role in producing anti-tumor activity. Considering all our results, we suggest that NPPA-PTX is a novel bioreductive PTX prodrug which could undergo further evaluation.

Recent studies showed that Guaiazulene (GA) and Sodium guaiazulene sulfonate (GAS-Na) have good anti-gastric ulcer effect. Here, two series of GA derivatives were synthesized and evaluated for their anti-gastric ulcer activity. The data obtained from in vivo testing of these compounds in a rodent ethanol-induced stomach injury model are discussed. Among the tested compounds, A1, A4, and A9 (ulcer index: 1.125 ± 1.246**, 1.714 ± 0.756*, 1.875 ± 1.126*) exhibited better anti-gastric ulcer activity than the positive control Omeprazole (2.005 ± 1.011*). The information got from these studies and the results of 3D-SAR investigation may be useful in the design of novel anti-gastric ulcer agents.

Microbial degradation of polyethylene (PE) mulching films has attracted much attention, but to date its relatively rapid biodegradation was limited. Here, a consortium of two bacterial isolates, Acinetobacter sp. strain NyZ450 and Bacillus sp. strain NyZ451 from the gut of PE-feeding Tenebrio molitor larvae (mealworms), was suggested to utilize PE, although each strain had no such ability alone. This consortium removed approximately 18% of PE film after 30 days at 23 °C. High-temperature gel permeation chromatography analysis indicated that the number-, weight-, and size-averaged molecular weights of PE were decreased by 14%, 24% and 21% from their respective initial values of 27,494 Da, 179,374 Da and 697,487 Da after a 20-day incubation with this consortium. Under scanning electron microscope, a biofilm formed by these strains was also observed on the film's surface. Fourier transform infrared spectroscopy analysis indicated that the films incubated with these two strains or either of them were all oxidized compared with the control without inoculation. Plate colony counting and electron microscopic observation showed that strain NyZ450 was predominant in the co-culture. This study enriched microbial resources for PE degradation and provided an example for the interaction of two bacterial strains for enhanced PE degradation.

c-Myc plays an important role in cell proliferation, differentiation, and cell apoptosis. FasL/Fas pathway is a key regulator of cell apoptosis. This study was aimed to investigate the effects of c-Myc on the FasL/Fas pathway in ischemia-reperfusion (I/R)-induced renal injury. Rats were objected to bilateral renal ischemia for 60 min and reperfused for 24 or 48 h. NRK-52E cells were treated with hypoxia-reoxygenation (H/R) or FasL. Immunohistochemistry was used to identify the distribution of c-Myc. Cell apoptosis was assessed by TUNEL staining. Ad-c-Myc and recombinant pcDAN 3.0 were used to overexpress c-Myc and c-FLIP, respectively. ChIP assay and luciferase assay were used to detect the binding of c-Myc to c-FLIP promoter. In I/R rats, c-Myc was increased significantly and mainly located in renal tubular epithelial cells; meanwhile, c-FLIP was decreased, cleaved caspase-8, cleaved caspase-3 and TUNEL-positive staining cells were increased. Treatment of I/R rats with c-Myc inhibitor 10058-F4 significantly attenuated the decrease in c-FLIP, the increase in cleaved caspase-8, cleaved caspase-3, TUNEL-positive cells, Scr and BUN in I/R rats. In NRK-52E cells, hypoxia and reoxygen induced the increase in c-Myc and decrease in c-FLIP. ChIP and luciferase assay results indicated that c-Myc binds to the promoter region of c-FLIP gene. Overexpression of c-Myc markedly decreased c-FLIP. Overexpression of c-FLIP inhibited the increase in cleaved caspase-8 and caspase-3 induced by FasL. Data indicated that c-Myc is increased in kidneys of I/R rats and negatively regulates the expression of c-FLIP, then enhanced FasL-induced cell apoptosis in I/R stress.

Inflammation and tubular cell death are the hallmarks of acute kidney injury. However, the precise mechanism underlying these effects has not been fully elucidated. Here we tested whether caspase-11, an inflammatory member of the caspase family, was increased in cisplatin or ischemia-reperfusion-induced acute kidney injury. Caspase-11 knockout mice after cisplatin treatment exhibited attenuated deterioration of renal functional, reduced tubular damage, reduced macrophage and neutrophil infiltration, and decreased urinary IL-18 excretion. Mechanistically, the upregulation of caspase-11 by either cisplatin or ischemia-reperfusion cleaved gasdermin D (GSDMD) into GSDMD-N, which translocated onto the plasma membrane, thus triggering cell pyroptosis and facilitated IL-18 release in primary cultured renal tubular cells. These results were further confirmed in GSDMD knockout mice that cisplatin-induced renal morphological and functional deterioration as well as urinary IL-18 excretion were alleviated. Furthermore, deficiency of GSDMD significantly suppressed cisplatin-induced IL-18 release but not the transcription and maturation level of IL-18 in tubular cells. Thus, our study indicates that caspase-11/GSDMD dependent tubule cell pyroptosis plays a significant role in initiating tubular cell damage, urinary IL-18 excretion and renal functional deterioration in acute kidney injury.

A series of magnesium and zinc complexes, [(L1–3)2M2(μ-OBn)2] (M = Mg (1–3), Zn (4–6)), have been synthesized by the reaction of NNO-tridentate ketiminate ligands (L1–3-H) and a stoichiometric amount of MgnBu2 (or ZnEt2) and BnOH. In addition, the reaction of these ketiminate ligands (L1–4-H) with a half equivalent of MgnBu2 (or ZnEt2) in toluene provides [M(L1–4)2] (M = Mg (7–10), Zn (11–14)) in good yields. All of these complexes have been fully characterized by NMR spectroscopy and elemental analysis, and the molecular structures of [(L1)2Mg2(μ-OBn)2] (1), [(L3)2Mg2(μ-OBn)2] (3), [(L1)2Zn2(μ-OBn)2] (4), [Mg(L1)2] (7), [Zn(L1)2] (11) and [Zn(L4)2] (14) have been further confirmed by X-ray crystallographic studies. X-ray diffraction studies revealed that complexes 1, 3 and 4 were dimeric in the solid state, bridging through the benzyloxy groups, while the solid-state structures of 7, 11 and 14 revealed a mononuclear species, six-coordinated by N, N, and O atoms of two ketiminate ligands, forming a distorted octahedron around the metal centre. Complexes 1–6 acted as efficient initiators for the ring-opening polymerization of lactides, producing PLAs with controlled molecular weights and narrow molecular weight distributions. Complex 6 [(L3)2Zn2(μ-OBn)2] exhibited the highest activity towards the ROP of lactides. And complexes 1–6 initiated rac-lactide polymerization to afford heterotactic enriched polymers (Pr up to 0.82). In addition, complexes 7–14 were also shown to efficiently catalyze the ring-opening polymerization of lactides in the presence of BnOH.

Small molecule modified anticancer drug conjugates (SMMDCs) can self-assemble into nanoparticles (NPs) as therapeutic NP platforms for cancer treatment. Here we demonstrate that the XlogP and Hansen solubility parameters of paclitaxel (PTX) SMMDCs is essential for SMMDCs self-assembling into NPs. The amorphous state of PTX SMMDCs will also affect SMMDCs self-assembling into NPs. However, the antitumor activity of these PTX SMMDCs NPs decreased along with their XlogP values, indicating that a suitable XlogP value for designing the SMMDCs is important for self-assembling into NPs and for possessing antitumor activity. For higher level XlogP SMMDCs, a degradable linker should be considered in the design of SMMDCs to overcome the problem of lower antitumor activity. It is preferable that the hydrophilic groups in the SMMDCs should be present on the surface of self-assembling NPs.

A new halocadmium/methyl viologen hybrid (MV)4(Cd2I6)(Cd2I7)2 (1) (MV2+ = methyl viologen) has been structurally determined. In 1, two kinds of dimeric halocadmium clusters constructed from edge/vertex-sharing CdI4 tetrahedra respectively, i.e., Cd2I6 2− and Cd2I7 − dimmers were observed, which were templated by methyl viologen cation (MV2+). A highly interesting feature of 1 is the presence of mixed type dimeric halocadmium clusters in one crystal lattice templated by one kind of cation. 1 displays photoluminescences, and its thermochromism behavior is observed, whose mechanism was verified by theoretical calculations.

Alkali metals were introduced into heavy main-group iodometallates to get two new IA/IVAheterometallic frameworks [PbI3K(pdon)(H2O)2] n (1) and {[Pb3 I 9 K 2(pdon)2(H3O)] ⋅H 2O} n (2) (pdon =1,10-phenanthroline-5,6-dione), which were obtained as single phases by hydrothermal method at different pH values. Compounds 1 and 2 are three-dimensional heterometallic frameworks constructed from the linkage of pdon ligand between iodometallate chains and potassium oxides/iodide clusters. Specially, these two heterometallic frameworks exhibit broadened absorption bands at 700 and 750 nm compared with those of bulk PbI2 and pdon ligand. The band gap of 2 is wider than that of 1, which is due to the absence of π⋯π interaction in 2. Their thermal stabilities are also discussed.