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The accumulation of nitrite is frequently overlooked, despite the fact that nitrification is the most essential phase of the entire nitrogen (N) cycle and that nitrifying bacteria play a significant role in nitrification. At present, the effects of different N application rates on soil nitrite-oxidizing bacteria (NOB) abundance, community composition, diversity, and its main influencing factors are still unclear. In this study, five N fertilizer application rates under film mulching and a drip irrigation system were studied in the semi-arid area of Northeast China. The treatments were 0 kg ha−1 (N0), 90 kg ha−1 (N1), 150 kg ha−1 (N2), 210 kg ha−1 (N3), and 270 kg ha−1 (N4). Fluorescent quantitative PCR and Illumina Miseq sequencing were used to analyze the abundance and community structure of NOB under different amounts of N application. The results showed that the increase in amounts of N application was strongly accompanied by an increase in the content of soil organic matter (SOM), total nitrogen (TN), nitrate nitrogen (NO3−-N), and ammonium nitrogen (NH4+-N), while the pH significantly reduced with an increase in N fertilization. N fertilization significantly increased soil nitrite oxidoreductase (NXR) activity, soil nitrification potential (PNR), and soil nitrite oxidation potential (PNO). A high N application rate significantly heightened the abundance of Nitrospira- and Nitrobacter-like NOB. N fertilizer considerably raised the Shannon index of Nitrospira-like NOB. The N application amount was the key factor affecting the community structure of Nitrospira-like NOB, and available nitrogen (AN) had the dominant influence on the community structure of Nitrospira-like NOB. N fertilizer can cause soil acidification, which affects NOB abundance and diversity. Nitrospira-like NOB may promote nitrite oxidation in different N application rates under a mulched fertigation system. The findings offered a crucial scientific foundation for further investigation into how nitrite-oxidizing bacteria respond to N fertilizer management strategies in farmland soil under film mulching drip irrigation in Northeast China. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID‐19), a global pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), has posed a catastrophic threat to human health worldwide. Human stem cell‐derived organoids serve as a promising platform for exploring SARS‐CoV‐2 infection. Several review articles have summarized the application of human organoids in COVID‐19, but the research status and development trend of this field have seldom been systematically and comprehensively studied. In this review, we use bibliometric analysis method to identify the characteristics of organoid‐based COVID‐19 research. First, an annual trend of publications and citations, the most contributing countries or regions and organizations, co‐citation analysis of references and sources and research hotspots are determined. Next, systematical summaries of organoid applications in investigating the pathology of SARS‐CoV‐2 infection, vaccine development and drug discovery, are provided. Lastly, the current challenges and future considerations of this field are discussed. The present study will provide an objective angle to identify the current trend and give novel insights for directing the future development of human organoid applications in SARS‐CoV‐2 infection. [ABSTRACT FROM AUTHOR]

This paper unveils a novel perspective on synthesis and characterization of the ligand 5-bromo-2-amino-2'-(phenyl-1H-imidazo[4,5-f][1,10]phenanthroline) (BAPIP), and its iridium(III) complexes [Ir(PPY−) 2 (BAPIP)](PF 6) (1a, with PPY− as deprotonated 2-phenylpyridine), [Ir(PIQ−) 2 (BAPIP)](PF 6) (1b, piq− denoting deprotonated 1-phenylisoquinoline), and [Ir(BZQ−) 2 (BAPIP)](PF 6) (1c, bzq− signifying deprotonated benzo[h]quinoline). Systematic evaluation of the cytotoxicity of 1a, 1b, and 1c across diverse cell lines encompassing B16, HCT116, HepG2, A549, HeLa, and LO2 using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. Unexpectedly, compounds 1b and 1c demonstrated no cytotoxicity against the above cell lines. Motivated by the pursuit of heightened anti-proliferative potential, a strategic encapsulation approach yielded liposomes 1alip, 1blip, and 1clip. As expectation, 1alip, 1blip, and 1clip displayed remarkable anti-proliferative efficacy, particularly noteworthy in A549 cells, exhibiting IC 50 values of 4.9 ± 1.0, 5.9 ± 0.1, and 7.6 ± 0.2 μM, respectively. Moreover, our investigation illuminated the mitochondrial accumulation of these liposomal entities, 1alip, 1blip, and 1clip, evoking apoptosis through the mitochondrial dysfunction mediated by reactive oxygen species (ROS). The ferroptosis was confirmed by decrease in glutathione (GSH) concentrations, the downregulation of glutathione peroxidase 4 (GPX4), increase of high mobility group protein 1 (HMGB1), and lipid peroxidation. Simultaneously, pyroptosis as another mode of cell death was undertaken. RNA-sequencing was employed to investigate intricate signalling pathways. In vivo examination provided tangible evidence of 1alip in effectively curbing tumor growth. Collectively, this study provides a multifaceted mode of cellular demise orchestrated by 1a, 1alip, 1blip, and 1clip, involving pathways encompassing apoptosis, ferroptosis, and pyroptosis. Three new iridium(III) complexes were synthesized and characterized. The anticancer activity of the complexes toward A549 cells were explored, the liposomes entrapped complexes exhibit high antitumor efficacy in vivo. [Display omitted] • Three new iridium(III) complexes and their liposomes were synthesized and characterized. • The cytotoxicity in vitro and in vivo of the complexes and their liposomes was investigated. • Apoptosis, reactive oxygen species and cell cycle arrest were examined. • The RNA-sequence were carried out. • The antitumor efficacy in vivo was studied. [ABSTRACT FROM AUTHOR]

To obtain porous starch granules with higher absorption capacities, three types of enzyme combinations were adopted to modify wheat and maize starches: (1) sequential α-amylase (AA) → glucoamylase (GA); (2) sequential branching enzyme (BE) → GA; and (3) sequential AA→BE→GA. The results indicated that AA→BE→GA treatment had a most optimal influence on porous starches. Compared to AA→GA and BE→GA, the mesopores in wheat starch granules treated with AA→BE→GA decreased by 52.82 and 48.70%, respectively. Conversely, the macropores increased by 216.68 and 138.18%, respectively. While for maize starch, the percentages of mesopores and macropores hardly changed after three enzyme combinations. Comparing the three enzyme treatments showed that pore volume (0.005 and 0.007 cm3/g) and pore size (36.35 and 26.54 nm) were largest in the AA→BE→GA treated wheat and maize starches, respectively. Compared to the AA→GA and BE→GA, the adsorption capacities for oil, dye and heavy metal ions, wheat starch treated with AA→BE→GA increased by 46.61 and 242.33%, and 44.52 and 134.41%, and 28.83 and 271.72%, respectively. Correspondingly, that of maize starch increased by 29.71 and 133.29%, and 42.92 and 79.93%, and 28.16 and 161.43%, respectively. These results may provide a new and valuable enzyme combination for optimising porous starch granules with higher absorption capacities. • Wheat and maize starches were treated with three types of enzyme combinations. • AA→BE→GA treatment had a most optimal influence on porous starches. • AA→BE→GA resulted in a greater reduction in amylose content and long side chains. • AA→BE→GA resulted in an obvious increment in specific surface area and pore size. • AA→BE→GA modified starches showed the most significant adsorption capacities. [ABSTRACT FROM AUTHOR]

Chlorophyll is the most important carrier of photosynthesis in plants and is therefore vital for plant growth and development. Synthesis of 5-aminolevulinic acid (ALA) is initiated and catalyzed by glutamyl-tRNA reductase (GluTR) and is the rate-limiting step in chlorophyll biosynthesis. GluTR is controlled by several regulating factors. Although many studies have investigated the structure and function of GluTR in plants, the maize (Zea mays L.) GluTR has not yet been reported. Here, we isolated and identified the first loss-of-function mutant of GluTR in plants from a maize mutagenic population. The stop-gain mutation in ZmGluTR1 resulted in leaf etiolation throughout the growing season. The level of intermediates of chlorophyll biosynthesis and photosynthetic pigments decreased markedly and abnormal chloroplast structure was also observed in the mutants. Further analysis revealed that the deletion of carboxyl terminal (C-terminal) led to premature transcription termination and this hindered the interaction with FLUORESCENT (FLU), thereby influencing the stability of mutated ZmGluTR1 and leading to abolish interaction with GluTR-binding protein (GluBP). Moreover, mutations in the catalytic domain or nicotinamide adenine dinucleotide phosphate (NADPH) binding domain were lethal under normal growth conditions. These results indicate that ZmGluTR1 plays a fundamental role in chlorophyll biosynthesis and maize development. • The first glutamyl-tRNA reductase gene was identified in maize. • The deletion of carboxyl terminal led to abolish interaction with ZmFLU and ZmGluBP. • ZmGluTR is essential not only for chlorophyll biosynthesis but also for maize growth and development. [ABSTRACT FROM AUTHOR]

Pseudomonas putida (P. putida) is a common spoilage microorganism that can cause food contamination and various foodborne illnesses. Rose essential oil (REO) is regarded as a good natural antibacterial agent because of its broad spectrum and excellent antibacterial properties. This study aimed to reveal the mechanism of action of REO on P. putida at the cellular level and to investigate the regulatory role of REO on the metabolic pathway of P. putida for the first time using the metabolome. The results demonstrated that the integrity of bacterial cell walls and membranes was disrupted, leakage of cell contents (proteins, ATP, and nucleic acids) occurred after the bacterial cell is treated with REO. The severe disruptive effect of REO on cell morphology was observed under scanning electron microscopy and transmission electron microscopy, further confirming the damage of REO on the cell wall and cell membrane. A total of 200 differential metabolites were screened at the metabolic level, of which 130 differential metabolites were significantly up-regulated, and 70 differential metabolites were significantly down-regulated. These differential metabolites were mainly involved in the TCA cycle, amino acid metabolism, nucleotide metabolism, carbohydrate metabolism, lipid metabolism, biosynthesis of pantothenic acid and coenzyme A, and aminoacyl tRNA biosynthesis, among which amino acid metabolism was most severely disrupted. Finally, the application results showed that the color, smell, and tissue state of white Hypsizygus marmoreus did not change significantly 8 days after REO treatment, indicating that REO has a good bacterial inhibitory effect on white Hypsizygus marmoreus. In conclusion, REO can inhibit P. putida at multiple targets and pathways, destroying cell morphological structure and disrupting metabolic processes. These results would provide new theoretical basis for the inhibition mechanism of REO on P. putida , and REO may be used as an effective alternative to chemical additives in the edible fungi industry. • Rose essential oil exhibited remarkably antibacterial activity against Pseudomonas Putida. • Rose essential oil disrupted cell walls and membranes. • Rose essential oil caused leakage of intracellular proteins, adenosine triphosphate, and nucleic acids. • 200 metabolites are differentially expressed with rose essential oil treatment. • Pathways associated with amino acid and nucleotide metabolism were mainly disrupted. [ABSTRACT FROM AUTHOR]

A new ligand 2-(1 E ,3 E ,5 E ,7 E)-2,6-dimethyl-8-(2,6,6-trimethylcyclohex-1-yl)octa-1,2,5,7-tetraen-1-yl)-1 H -imidazo[4,5-f][1,10]phenanthroline (DTOIP) was synthesized and combined with [Ir(ppy) 2 Cl] 2 ·2H 2 O (ppy = deprotonated Hppy: 2-phenylpyridine), [Ir(piq) 2 Cl] 2 ·2H 2 O (piq = deprotonated Hpiq: 1-phenylisoquinoline) and [Ir(bzq) 2 Cl] 2 ·2H 2 O (bzq = deprotonated Hbzq: benzo[h]quinolone) to form [Ir(ppy) 2 (DTOIP)](PF 6) (Ir1), [Ir(piq) 2 (DTOIP)](PF 6) (Ir2), and [Ir(bzq) 2 (DTOIP)](PF 6) (Ir3), respectively. The complexes were characterized by elemental analysis, high-resolution mass spectrometry (HRMS), 1H NMR and 13C NMR. The antiproliferative activity of the complexes toward B16, BEL-7402, Eca-109 and normal LO2 cells was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. Complexes Ir1 , Ir2 and Ir3 showed high antiproliferative activity against B16 cells with a low IC 50 values of 0.4 ± 0.1, 2.0 ± 0.1 and 1.4 ± 0.09 μM, respectively. Three-dimensional (3D) in vitro cell models also demonstrated that the iridium(III) complexes have a remarkable cytotoxicity to B16 cells. The experiments of cellular uptake, mitochondrial localization, and intracellular distribution of the drugs proved that the three iridium(III) complexes can enter the mitochondria, leading to the loss of mitochondrial membrane potential (MMP), decreased glutathione (GSH) levels, causing an increase of intracellular ROS content, and DNA damage, finally inducing apoptosis. RNA-sequence and bioinformatics analyses were used to analyze the differentially expressed genes and enriched biology processes. Antitumor in vivo demonstrated that complex Ir1 (5 mg/kg) exhibits a high efficacy to inhibit the tumor growth with an inhibitory rate of 71.67%. These results show that the complexes may be potent anticancer candidate drugs. Three new iridium(III) complexes [Ir(ppy) 2 (DTOIP)](PF 6) (Ir1) (DTOIP = 2-(1 E ,3 E ,5 E ,7 E)-2,6-dimethyl-8-(2,6,6-trimethylcyclohex-1-yl)octa-1,2,5,7-tetraen-1-yl)-1 H -imidazo[4,5-f][1,10]phenanthroline, ppy = deprotonated 2-phenylpyridine), [Ir(piq) 2 (DTOIP)](PF 6) (Ir2) (piq = deprotonated 1-phenylisoquinoline) and [Ir(bzq) 2 (DTOIP)](PF 6) (Ir3) (bzq = deprotonated benzo[h]quinolone) were synthesized. The cytotoxicity of the complexes against B16, BEL-7402, A549, Eca-109 cancer cells and normal LO2 was evaluated using 3-(4,5-dimethylthiazole-2-yl)-2,5-biphenyl tetrazolium bromide (MTT) method. The inhibitory rate in vivo reaches 71.67% for Ir1. [Display omitted] • Three new iridium(III) complexes were synthesized and characterized. • The cytotoxicity in vitro and in vivo of the complexes was investigated. • Apoptosis, reactive oxygen species and cell cycle arrest were carried out. • The distribution of the complexes in the cytoplasm, mitochondria and nuclei were explored. • The antitumor efficacy in vivo was investigated. [ABSTRACT FROM AUTHOR]

Combining the ligand NPIP (2-(2-nitrophenyl)-1 H -imidazo[4,5-f][1,10]phenanthroline) with piq (1-phenylisoquinoline) and bzq (benzo[ h ]quinolone) gave [Ir(piq) 2 (NPIP)](PF 6) (Ir1), and [Ir(bzq) 2 (NPIP)](PF 6) (Ir2). The newly synthesized complexes were characterized by high-resolution mass spectrometry (HRMS), 1H NMR and 13C NMR. The complexes showed high antiproliferative activity against B16 cells. Three-dimensional (3D) cell model in vitro was used to evaluate the inhibitory effect of iridium (III) complex on B16 cells. The cellular uptake, mitochondrial localization, and intracellular distribution of the drugs confirmed that the iridium (III) complexes targeted the mitochondria, and the complexes can lead to the loss of mitochondrial membrane potential (MMP), increases the intracellular ROS content, further induces apoptosis. We also found that Ir1 and Ir2 can trigger the release of damage-associated molecular patterns (DAMPs) (cell surface calreticulin (CRT), heat-shock protein 70 (HSP70) and high mobility group box 1 (HMGB1)). In addition, Ir1 and Ir2 inhibited glutathione (GSH) synthesis and thus induced oxidative stress, Ir1 and Ir2 promoted malondialdehyde (MDA) production which is the stable metabolite of lipid peroxidation products. Finally, mice xenograft assay was performed to demonstrate that the complex shows higher antitumor activity in vivo than cisplatin. The inhibitory rates for cisplatin and Ir1 are 38.95% and 69.67%, respectively. Two new iridium(III) complexes were synthesized. The complexes show higher cytotoxic activity than cisplatin against B16 cells. The studies on anticancer in vivo demonstrates that the complex Ir1 can effectively inhibit the tumor growth with an inhibitory rate of 69.67%. [Display omitted] • Two new iridium(III) complex was synthesized and characterized. • The cytotoxicity in vitro and in vivo of the complex was investigated. • Apoptosis, reactive oxygen species and cell cycle arrest were performed. • The location and mitochondrial membrane potential were explored. • The expression of B-cell lymphoma-2 family proteins was assayed. [ABSTRACT FROM AUTHOR]

• Wheat starch was modified with transglucosidase to increase branching degree. • The branching degree increased with increasing transglucosidase treatment time. • Transglucosidase resulted in the reduction in the crystallinity of retrograded starch. • Water mobility of transglucosidase-treated starch increased during retrogradation. • Transglucosidase resulted in the reduction in retrogradation rate constant of starch. To reduce the wheat-flour-based food texture and flavor deterioration caused by starch retrogradation, herein wheat starch, the most ingredient in wheat flour, was modified by transglucosidase to delay long-term retrogradation of wheat starch. The study proposed promising data of transglucosidase-treated starch about structure, crystallinity and retrogradation kinetics. Structural properties showed that transglucosidase treatment shortened the average chain length from 19.49 to 16.10 and induced the dominance of amorphous state. Moreover, branching degree increased from 14.11% to 17.97% after transglucosidase treatment, resulting in higher water mobility. Amylose content increased from 25.33% to 59.00% due to the hydrolysis ability of transglucosidase. Relative crystallinity of the retrograded starches decreased from 24.33% to 14.50%. Furthermore, the Avrami parameters demonstrated that transglucosidase treatment significantly retarded the retrogradation rate of wheat starch due to the decrease of re-crystalline rate. The outcoming would supply a solid theory foundation for exploring the wheat staple foods with higher qualities. [ABSTRACT FROM AUTHOR]

Soil microorganisms directly participate in phosphorus (P) cycle, which in turn affects crop yield and quality. However, how biological and chemical parameters respond to mineral P fertilizer application rates in rhizosphere soil remains unclear. Here, a pot experiment was conducted to investigate the effects of different mineral P fertilizer application rates (0, 60, 120, and 300 kg P2O5 ha−1) on soil chemical properties and bacterial community in maize rhizosphere in a Mollisol. With increasing P fertilizer rates, soil organic carbon concentration decreased, while soil Olsen P and inorganic P and organic P (Po) fractions concentrations increased. High-throughput 16S rRNA gene sequencing showed that the relative abundances of some beneficial bacteria (Anaerolinea, Anaeromyxobacter, Kaistia and Rhodobacter) significantly increased with reduced P fertilizer rates, and meanwhile those of other beneficial bacteria (Mesorhizobium, Microvirga, Rhizobacter and Skermanella) significantly decreased under high P fertilizer rates. Redundancy analysis (RDA) showed that labile Po was the main driver of the differences in bacterial community structure. Bacterial community diversity and composition significantly and indirectly affected maize yield via octacalcium-bound P, occluded Fe/Al-bound P, labile Po, and moderately labile Po. The results suggested that reducing P fertilizer rates can promote beneficial bacterial growth and increase bacterial community diversity. [ABSTRACT FROM AUTHOR]

Summary: Background: Psychological stress is a possible factor in the disease course and poor psychosocial outcomes in inflammatory bowel disease (IBD). Understanding the exact relationship between stress and health has been hampered by methodological issues and how stress has been defined and measured. Aims: To explore the association between stress and disease outcomes, investigate the impact of stress on psychosocial outcomes, and evaluate the efficacy of interventions in reducing stress for people with IBD Methods: We performed a systematic review, searching Medline, CINAHL, Embase and PsycInfo databases on 21 January 2021. We included prospective studies that recruited people with IBD who were aged 16 or over and that measured psychological stress or distress. Analyses included Critical Appraisal Skills Programme quality assessments of included studies and narrative analyses against each research question. Results: We reviewed 38 studies with 4757 people with IBD, and included 23 observational and 15 interventional studies using 36 different instruments to measure stress. Perceived stress was the most frequently studied concept and preceded IBD exacerbation. Only three studies examined the relationship between stress and psychosocial factors. Cognitive behavioural interventions may reduce stress and other interventions with disease‐specific stress, but more studies are needed where groups have comparable baseline characteristics and potential harms are considered alongside benefits. Conclusion: Psychological stress appears to precede IBD exacerbation, although what role it plays in psychosocial outcomes and how it is best managed is unclear. Further research needs to examine the differential effects of stress on disease subtypes and IBD in flare and remission. [ABSTRACT FROM AUTHOR]

The main varieties of Echinopsis Radix recorded in the Chinese Pharmacopoeia are the roots of Echinops latifolius Tausch or Echinops grijsii Hance. However, the chemical constituents and biological activities of this herb have not been reviewed. In order to clarify the chemical constituents of the main varieties of this herb and improve the quality of Chinese medicinal material resources, this paper systematically reviewed their chemical constituents and related biological activities. Phytochemical investigations reveal eighty-five compounds including fort y-nine thiophenes (1–49), eight flavonoids (50–57), seven caffeic acids and its derivatives (58–64), eight sesquiterpenoids (65–72), and thirteen triterpenoids and other compounds (73–85) were reported from Echinopsis Radix. The review of biological activities suggests that thiophenes are the main secondary metabolites of the medicinal material which exert antitumor, insecticidal and antifungal activities. In addition, caffeic acid and its derivatives and sesquiterpenes are potential active ingredients worthy of further study. This review provides an important scientific basis for the development of active ingredients and resource quality evaluation of Echinopsis Radix. [ABSTRACT FROM AUTHOR]

The large agglomeration of starch paste in hot water, and fast retrogradation tendency and low transparency of starch gel restrict widespread application of kudzu starch. To improve the above defects, kudzu starch was modified with sequentially α-amylase (AA) and transglucosidase (TG), the latter for varying times. The results indicated that, compared to kudzu starch, amylose content and molecular weight of AA/TG-treated starches reduced by 20.07% and 69.50%, respectively. The proportion of A chain increased by 68.68%, whereas B1, B2 and B3 chains decreased by 14.28%, 48.29% and 23.44%, respectively. The degree of branching dramatically increased by 128.3%. After AA→TG treatment, the changes of starch structure enhanced the functional properties of kudzu starch. The solubility, paste clarity and gelatinization temperature increased, whereas the relative crystallinity, viscosity, storage and loss moduli decreased. Overall, the AA→TG modification would be desirable to improve the functional properties of kudzu starch to expand more large-scale application. [ABSTRACT FROM AUTHOR]

Trichocyte keratins hold significant promise in accelerating wound healing. Yet it is difficult to discriminate characteristics and mechanisms from their subtypes because of the high sequence homology. Here, the distinct wound healing properties in terms of wound closure rate, epidermal regeneration and angiogenesis of 17 kinds of human hair keratins is reported. Each trichocyte keratin shows distinct behaviors with unique advantages. Amongst all, recombinant keratin (RK) 33B, RK34, RK39 and RK84 show the highest efficiency in wound closure acceleration, and RK34, RK37 and RK81 presented the strongest angiogenic performance. Furthermore, transcriptomic analysis revealed the regulatory mechanisms of trichocyte keratins in the proliferation and migration of keratinocyte and blood vessel generation. Finally, the keratins with strong re-epithelialization and angiogenic performances significantly accelerate wound closure in a diabetic rat model established in-house. The findings provide a panorama view of trichocyte keratin performance in wound healing and that may harbor potential for finely tailored keratin development and precision applications. [ABSTRACT FROM AUTHOR]

A new ligand DFIP (2-(dibenzo[b,d]furan-3-yl)-1H-imidazo[4,5-f][1,10]phenanthroline) and its two complexes iridium(III) [Ir(ppy)2(DFIP)](PF6) (ppy = 2-phenylpyridine, Ir1) and ruthenium(II) [Ru(bpy)2(DFIP)](PF6)2 (bpy = 2,2′-bipyridine, Ru1) were synthesized and characterized. The anticancer effects of the two complexes on A549, BEL-7402, HepG2, SGC-7901, HCT116 and normal LO2 cells were tested by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. Complex Ir1 shows high cytotoxic activity on A549, BEL-7402, SGC-7901 and HepG2, Ru1 exhibits moderate anticancer activity toward A549, BEL-7402 and SGC-7901 cells. The IC50 values of Ir1 and Ru1 toward A549 are 7.2 ± 0.1 and 22.6 ± 1.4 μM, respectively. The localization of complexes Ir1 and Ru1 in the mitochondrial, intracellular accumulation of reactive oxygen species (ROS) levels, and the changes of mitochondrial membrane potential (MMP) and cytochrome c (cyto-c) were investigated. Apoptosis and cell cycle were detected by flow cytometry. Immunogenic cell death (ICD) was used to detect the effects of Ir1 and Ru1 on the A549 using a confocal laser scanning microscope. The expression of apoptosis-related proteins was detected by western blotting. Ir1 and Ru1 can increase the intracellular ROS levels and release cyto-c, reduce the MMP, leading to the apoptosis of A549 cells and blocking the A549 cells at the G0/G1 phase. Additionally, the complexes caused a decrease of the expression of polyADP-ribose polymerase (PARP), caspase 3, Bcl-2 (B-cell lymphoma-2), PI3K (phosphoinositide-3 kinase) and upregulated the expression of Bax. All these findings indicated that the complexes exert anticancer efficacy to induce cell death through immunogenic cell death, apoptosis, and autophagy. [ABSTRACT FROM AUTHOR]

This study was intended to evaluate the anticancer activity of three newly synthesized iridium(III) complexes [Ir(ppy)2(PEIP)](PF6) (1) (ppy = 2-phenylpyridine, PEIP = 2-phenethyl-1H-imidazo[4,5-f][1,10]phenanthroline), [Ir(ppy)2(SIP)](PF6) (2) (SIP = (E)-2-styryl-1H-imidazo[4,5-f][1,10]phenanthroline) and [Ir(ppy)2(PEYIP)](PF6) (3) (PEYIP = 2-phenethynyl-1H-imidazo[4,5-f][1,10]phenanthroline). The cytotoxic activity in vitro against A549, SGC-7901, HepG2, HeLa and normal NIH3T3 cells was investigated by 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) method. We found that the complexes 1, 2 and 3 significantly inhibited cell proliferation, in particular, complexes 2 and 3 show high cytotoxic effect on SGC-7901 cells with an IC50 value of 5.8 ± 0.7 and 4.4 ± 0.1 μM. Moreover, cell cycle assay revealed that the complexes could block G2/M phase of the cell cycle. Apoptotic evaluation by Annexin V/PI staining indicated that complexes 1–3 can induce apoptosis in SGC-7901 cells. In addition, microscopy detection suggested that disruption of mitochondrial functions, characterized by increased generation of intracellular ROS and Ca2+ as well as decrease of mitochondrial membrane potential. Western blot analysis shows that the complexes upregulate the expression of pro-apoptotic Bax and downregulate the expression of anti-apoptotic Bcl-2, which further activates caspase-3 and prompts the cleavage of PARP. Taken together, these results demonstrated that complexes 1–3 exert a potent anticancer effect on SGC-7901 cells via ROS-mediated endoplasmic reticulum stress-mitochondrial apoptotic pathway and have a potential to be developed as novel chemotherapeutic agents for human gastric cancer. Three new iridium(III) complexes [Ir(ppy)2(PEIP)](PF6) (1) (ppy = 2-phenylpyridine, PEIP = 2-phenethyl-1H-imidazo[4,5-f][1,10]phenanthroline), [Ir(ppy)2(SIP)](PF6) (2) (SIP = 2-styryl-1H-imidazo[4,5-f][1,10]phenanthroline) and [Ir(ppy)2(PEYIP)](PF6) (3) (PEYIP = 2-phenethynyl-1H-imidazo[4,5-f][1,10]phenanthroline) were synthesized and characterized. The anticancer activity in vitro was investigated by 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) method. The results show that the complexes induce apoptosis via ROS-mediated endoplasmic reticulum stress-mitochondrial dysfunction pathway. [ABSTRACT FROM AUTHOR]

OBJECTIVES:Some studies suggest that eradication of Helicobacter pylori (Hp) might increase the risk of gastroesophageal reflux disease (GERD) in a portion of patients. We aimed to conduct a meta-analysis to investigate this.METHODS:A comprehensive, English, multiple-source literature search was performed from 1983 to February 2007. Only randomized controlled trial (RCT) and cohort studies comparing the prevalence of GERD in patients free from GERD at baseline with Hp eradication vs. those with persistent Hp were included. Quality of RCTs and cohorts was assessed by Jadad and New Castle-Ottawa scores, respectively. Meta-analysis of pooled odds ratios (ORs) was performed using Review Manager 4.2.10.RESULTS:Twelve (7 RCTs and 5 cohorts) of 271 articles were included. In six RCTs using erosive GERD as outcome, the OR for the frequency of GERD in Hp eradicated group vs. persistent Hp group was 1.11 (0.81–1.53, P=0.52). In five RCTs using symptomatic outcome, the OR for the frequency of GERD in Hp eradicated group vs. persistent Hp was 1.22 (0.89–1.69, P=0.22). In cohort studies, the OR for the frequency of GERD in Hp eradicated group vs. persistent Hp was 1.37 (0.89–2.12; P=0.15). Test of heterogeneity was not significant for any analyses. The results were consistent in subgroup and sensitivity analyses, including cohort studies vs. RCTs, high-quality studies vs. low-quality studies, and use of endoscopic vs. symptomatic outcomes except for the subgroup of patients with peptic ulcer disease (PUD) in cohort studies (OR: 2.04 (1.08–3.85); P=0.03).CONCLUSIONS:There is no association between Hp eradication and development of new cases of GERD in the population of dyspeptic patients. However, in cohort studies, there seems to be a twofold higher risk of development of erosive GERD in patients with PUD. The effect in RCTs of patients with PUD did not show a significant difference. [ABSTRACT FROM AUTHOR]

The study was intended to determine the antineoplastic effects of two new iridium(III) complexes [Ir(ppy)2(PTTP)](PF6) (1) (ppy = 2-phenylpyridine) and [Ir(piq)2(PTTP)](PF6) (2) (piq = 1-phenylisoquinoline, PTTP = 2-phenoxy-1,4,8,9-tetraazatriphenylene). In MTT assay, the ligand PTTP displayed ineffective inhibition on cell growth in SGC-7901, BEL-7402, HepG2 as well as NIH3T3 cell lines, while complexes 1 and 2 showed high cytotoxic activity on SGC-7901 cells with an IC50 value of 0.5 ± 0.1 µM and 4.4 ± 0.6 µM, respectively. Cellular uptake, cell cloning experiments, wound healing assay and cell cycle arrest indicated that the two complexes can inhibit the cell proliferation in SGC-7901 and induce cell cycle arrest at G0/G1 phase. Additionally, reactive oxygen species (ROS) and mitochondrial membrane potential suggested that the two complexes induced cell apoptosis through disrupting mitochondrial functions. Further, western blot analysis illustrated that the two complexes caused apoptosis via regulating expression levels of Bcl-2 family proteins. Moreover, complex 1 could suppress tumor growth in vivo with an inhibitory rate of 49.41%. Altogether, these results demonstrated that complexes 1 and 2 exert a potent anticancer effect against SGC-7901 cells via mitochondrial apoptotic pathway and have a potential to be developed as antineoplastic drug candidates for human gastric cancer. [ABSTRACT FROM AUTHOR]

In this paper, two new iridium(III) complexes [Ir(ppy) 2 (CBIP)](PF 6) (ppy = 2-phenylpyridine, CBIP = 2-(4′-chloro-(1,1′-biphenyl))-1 H -imidazo[4,5-f][ 1 , 10 ]phenanthroline) (Ir1) and [Ir(piq) 2 (CBIP)](PF 6) (piq = 1-phenylisoquinoline) (Ir2) were synthesized and characterized. The anticancer activity of the complexes against cancer A549, HepG2, SGC-7901, BEL-7402, HeLa and LO2 cells was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. Unexpectedly, the complexes exhibit no or low cytotoxic activity toward the selected cancer cells. To increase the anticancer activity, complexes Ir1 and Ir2 were encapsulated into the liposome to form Ir1lipo and Ir2lipo , while Ir1lipo and Ir2lipo show high cytotoxic efficacy against BEL-7402, SGC-7901 and HeLa cells and Ir2lipo displays moderate cytotoxic activity against A549 and HepG2. The anticancer mechanism was explored through wound healing, cell cycle arrest, apoptosis, the change of mitochondrial membrane potential and antitumor activity in vivo. The antitumor in vivo showed that Ir1Lipo (3.9 mg/kg) exhibited significant antitumor activity with an inhibitory rate of 62.16%. Additionally, the expression of B-cell lymphoma-2 family proteins was studies by western blotting analysis. The results demonstrate that Ir1lipo and Ir2lipo induce apoptosis in BEL-7402 cells via endoplasmic reticulum stress-mitochondrial pathway. [Ir(ppy) 2 (CBIP)](PF 6) (ppy = 2-phenylpyridine, Ir1), [Ir(piq) 2 (CBIP)](PF 6) (piq = 1-phenylisoquinoline, CBIP = 2-(4′-chloro-(1,1′-biphenyl))-1 H -imidazo[4,5-f] [1,10]phenanthroline, Ir2), complex-loaded liposomes Ir1lipo and Ir2lipo were synthesized. The anticancer activity in vitro and in vivo of the complexes and their liposomes were evaluated. [Display omitted] • Three iridium(III) complexes and complex-loaded liposomes were synthesized. • The cytotoxicity in vitro and in vivo of the complexes and liposomes was studied. • The apoptosis and cell cycle arrest were performed. • The location of the complexes at the endoplasm reticulum and mitochondria was explored. • The expression of B-cell lymphoma-2 family proteins was assayed. [ABSTRACT FROM AUTHOR]

In this report, a new ligand TFBIP (TFBIP = 2-(4′-trifluoromethyl)-[1,1′-biphenyl]-4-yl)-1 H -imidazo[4,5-f][1,10]phenanthroline) and its three iridium (III) complexes [Ir(ppy) 2 (TFBIP)](PF 6) (Ir1 , ppy = 2-phenylpyridine), [Ir(bzq) 2 (TFBIP)](PF 6) (Ir2 , bzq = benzo[ h ]quinolone) and [Ir(piq) 2 (TFBIP)](PF 6) (Ir3 , piq = 1-phenylisoquinoline) were synthesized and characterized. The cytotoxicity in vitro of the complexes toward several cancer cells was evaluated by 3-(4,5-dimethylthiazole-2-yl)-2,5-biphenyl tetrazolium bromide (MTT) methods. The complexes show no cytotoxicity (IC 50 > 100 μM) against these cancer cells. To enhance anticancer activity, these complexes were trapped in liposomes to form Ir1Lipo , Ir2Lipo and Ir3Lipo. The liposomes Ir1Lipo , Ir2Lipo and Ir3Lipo exhibit high or moderate cytotoxic activity. In particular, Ir1Lipo can effectively inhibit the cell growth with a low IC 50 value (< 10 μM) toward A549, HepG2, BEL-7402, B16, HeLa and SGC-7901 cells. Surprisingly, Ir1Lipo has no cytotoxic activity against the normal cell LO2 (IC 50 > 100 μM). The apoptosis and pyroptosis were investigated. Ir3Lipo induces apoptosis with a high early apoptotic number of 37%. The reactive oxygen species (ROS) levels, mitochondrial permeability transition pore open and mitochondrial membrane potential were detected. The intracellular Ca2+ concentration and release of cytochrome c were investigated. The expression of Bcl-2 (B-cell lymphoma-2) family proteins was explored by western blot. The antitumor activity in vivo of Ir1Lipo was evaluated with an inhibitory rate of 53%. Iridium(III) complexes were synthesized and characterized. These complexes display no cytotoxic activity. However, the complexes were encapsulated into the liposomes to form Ir1Lipo , Ir2Lipo and Ir3Lipo , Ir1Lipo show high anticancer efficacy toward the selected cancer cells. The anticancer effect in vivo of Ir1Lipo was investigated. [Display omitted] • Three iridium(III) complexes and their liposomes were synthesized and characterized. • The cytotoxicity in vitro and in vivo of the complexes and liposomes was studied. • The apoptosis, pyroptosis and cell cycle arrest were performed. • Reactive oxygen species levels and mitochondrial membrane potential were investigated. • The expression of Bcl-2 family proteins was assayed by western blot analysis. [ABSTRACT FROM AUTHOR]

The studies of iridium (III) complexes as potent anticancer reagents have attracted great attention. Here, a new iridium (III) complex [Ir(bzq) 2 (PYIP)](PF 6) (Ir1 , bzq = benzo[ h ]quinoline, PYIP = 2-(pyren-1-yl)-1 H -imidazo[4,5- f ][1,10]phenanthroline) was synthesized and its liposomes (Ir1Lipo) was prepared. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method was used to detect the cytotoxic activity of Ir1 and Ir1Lipo on HepG2, SGC-7901, BEL-7402, HeLa, B16, A549 and normal NIH3T3 cells. The complex Ir1 displays no obvious inhibitory effect on the growth of BEL-7402 cells, while the Ir1Lipo shows significant cytotoxic activity on BEL-7402 cells (IC 50 = 2.6 ± 0.03 μM). In further studies, Ir1Lipo induced apoptosis by the mitochondrial pathways, such as increasing intracellular reactive oxygen species (ROS) content and intracellular Ca2+ level, decreasing the mitochondrial membrane potential (MMP). In addition, after incubation with Ir1Lipo , the colony formation of BEL-7402 cells was significantly inhibited. Moreover, flow cytometry was used to detect the impact of Ir1Lipo on cell cycle distribution, and western blot was used to detect the expression of caspases and Bcl-2 (B-cell lymphoma-2) family proteins. Furthermore, Ir1Lipo exhibited significant antitumor activity in vivo with an inhibitory rate of 65.8%. These results indicated that Ir1Lipo induces apoptosis in BEL-7402 cells through intrinsic mitochondrial pathway. Synthesis of iridium(III) complex: [Ir(bzq) 2 (PYIP)](PF 6) (bzq = benzo[ h ]quinoline, PYIP = 2-(pyren-1-yl)-1 H -imidazo[4,5- f ][1,10]phenanthroline) (Ir1) and Ir1 -loaded liposomes Ir1Lipo. The anticancer effect of the complex and Ir1Lipo on several cancer cells were investigated by in vitro and in vivo experiments. Ir1 shows no cytotoxic activity, whereas Ir1Lipo displays high anticancer effect. [Display omitted] • Iridium(III) complex Ir1 was synthesized and encapsulated into liposomes Ir1Lipo. • The cytotoxicity in vitro of Ir1 and Ir1Lipo was investigated. • The apoptosis and cell cycle arrest were assayed by flow cytometry. • Reactive oxygen species (ROS) and mitochondrial membrane potential were explored. • The expression of Bcl-2 (B-cell lymphoma-2) family proteins was assayed by western blot. [ABSTRACT FROM AUTHOR]

In this report, we synthesized three new iridium(III) complexes: [Ir(piq) 2 (apip)]PF 6 (Ir1 , piq = 1-phenylisoquinoline, apip = 2-aminophenyl-1 H -imidazo[4,5-f][1,10]phenanthroline), [Ir(piq) 2 (maip)]PF 6 (Ir2 , maip = 3-aminophenyl-1 H -imidazo[4,5-f][1,10]phenanthroline) and [Ir(piq) 2 (paip)]PF 6 (Ir3 , paip = 4-aminophenyl-1 H -imidazo[4,5-f][1,10]phenanthroline). The DNA binding was investigated. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method was used to detect the cytotoxic activity of Ir1 , Ir2 and Ir3 , the complexes show highly active against B16 cells with IC 50 values of 0.3 ± 0.2 μM, 3.7 ± 0.2 μM and 4.6 ± 1.1 μM, respectively. Subsequently, cellular uptake suggested that the cytotoxicity of the complexes is attributed to their differences in cellular uptake levels. In addition, complexes Ir1 , Ir2 and Ir3 induce cell cycle arrest at the G0/G1 phase and regulate the cell cycle mediators such as cyclin D1, CDK6 (cyclin-dependent kinase 6), CDK4 and p21, leading to the inhibition of B16 cells proliferation. The autophagy was investigated by monodansylcadaverine (MDC) staining. The complexes can promote the change from LC3-I to LC3-II, up-regulate levels of Beclin-1 and down-regulate expression of p62. The complexes induced apoptosis by regulating the expression levels of related indicators such as PARP (poly ADP-ribose polymerase), PI3K (phosphoinositide-3 kinase), AKT (protein kinase B), Caspase, Bcl-2 (B-cell lymphoma-2), Bad (Bcl2 associated death promoter), Bax (Bcl2-associated X) and Cyto C (cytochrome C). Additionally, Ir1 exerted significant antitumor activity in the suppression of malignant melanoma proliferation in vivo. As indicated in the above results, these complexes were highly effective for malignant melanoma treatment through the intrinsic pathway and provided much insight into anticancer drugs for tumor therapy. Three new iridium(III) complexes: [Ir(piq) 2 (apip)]PF 6 (Ir1 , piq = 1-phenylisoquinoline, apip = 2-aminophenyl-1 H -imidazo[4,5-f][1,10]phenanthroline), [Ir(piq) 2 (maip)]PF 6 (Ir2 , maip = 3-aminophenyl-1 H -imidazo[4,5-f][1,10]phenanthroline) and [Ir(piq) 2 (paip)]PF 6 (Ir3 , paip = 4-aminophenyl-1 H -imidazo[4,5-f][1,10]phenanthroline) were synthesized and characterized. The cytotoxicity of the complexes against B16 cancer cells were investigated. Ir1 shows high antitumor activity with an inhibitory of 89.12%. [Display omitted] • Three new iridium(III) complexes were synthesized and characterized. • The cytotoxicity in vitro and in vivo of the complexes was investigated. • The apoptosis and cell cycle arrest were assayed by flow cytometry. • The expression of B-cell lymphoma-2 family proteins was investigated by western blot. • The antitumor in vivo shows that Ir1 exhibits high antitumor efficiency. [ABSTRACT FROM AUTHOR]