ABSTRACT
BACKGROUND: Prediabetes, which is a precedent of overt diabetes, is a known risk factor for adverse cardiovascular outcomes. Its impact on adverse cardiovascular outcomes in patients with cancer who are prescribed anthracycline-containing chemotherapy (ACT) is uncertain. The objective of this study was to evaluate the association of prediabetes with cardiovascular events in patients with cancer who are prescribed ACT. METHODS: The authors identified patients with cancer who received ACT from 2000 to 2019 from Clinical Data Analysis Reporting System of Hong Kong. Patients were divided into diabetes, prediabetes, and normoglycemia groups based on their baseline glycemic profile. The Primary outcome, a major adverse cardiovascular event (MACE), was the composite event of hospitalization for heart failure and cardiovascular death. RESULTS: Among 12,649 patients at baseline, 3997 had prediabetes, and 5622 had diabetes. Over median follow-up of 8.7 years, the incidence of MACE was 211 (7.0%) in the normoglycemia group, 358 (9.0%) in the prediabetes group, and 728 (12.9%) in the diabetes group. Compared with normoglycemia, prediabetes (adjusted hazard ratio [HR], 1.20; 95% confidence interval [CI], 1.01-1.43) and diabetes (adjusted HR, 1.46; 95% CI, 1.24-1.70) were associated with an increased risk of MACE. In the prediabetes group, 475 patients (18%) progressed to overt diabetes and exhibited a greater risk of MACE (adjusted HR, 1.76; 95% CI, 1.31-2.36) compared with patients who remained prediabetic. CONCLUSIONS: In patients with cancer who received ACT, those who had prediabetes at baseline and those who progressed to diabetes at follow-up had an increased risk of MACE. The optimization of cardiovascular risk factor management, including prediabetes, should be considered in patients with cancer who are treated before and during ACT to reduce cardiovascular risk. PLAIN LANGUAGE SUMMARY: Patients with cancer who have preexisting diabetes have a higher risk of cardiovascular events, and prediabetes is often overlooked. In this study of 12,649 patients with cancer identified in the Clinical Data Analysis Reporting System of Hong Kong who were receiving treatment with anthracycline drugs, prediabetes was correlated with increased deaths from cardiovascular disease and/or hospitalizations for heart failure. Patients who progressed from prediabetes to diabetes within 2 years had an increased risk of combined hospitalization for heart failure and death from cardiovascular disease. These findings indicate the importance of paying greater attention to cardiovascular risk factors, including how prediabetes is managed, in patients who have cancer and are receiving chemotherapy with anthracyclines, emphasizing the need for surveillance, follow-up strategies, and consideration of prediabetes management in cancer care.
Subject(s)
Anthracyclines , Neoplasms , Prediabetic State , Humans , Prediabetic State/epidemiology , Prediabetic State/chemically induced , Prediabetic State/complications , Anthracyclines/adverse effects , Anthracyclines/therapeutic use , Male , Female , Middle Aged , Neoplasms/drug therapy , Neoplasms/epidemiology , Aged , Hong Kong/epidemiology , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/chemically induced , Adult , Risk Factors , Diabetes Mellitus/epidemiology , IncidenceABSTRACT
Limited by the strong oxidation environment and sluggish reconstruction process in oxygen evolution reaction (OER), designing rapid self-reconstruction with high activity and stability electrocatalysts is crucial to promoting anion exchange membrane (AEM) water electrolyzer. Herein, trace Fe/S-modified Ni oxyhydroxide (Fe/S-NiOOH/NF) nanowires are constructed via a simple in situ electrochemical oxidation strategy based on precipitation-dissolution equilibrium. In situ characterization techniques reveal that the successful introduction of Fe and S leads to lattice disorder and boosts favorable hydroxyl capture, accelerating the formation of highly active γ-NiOOH. The Density Functional Theory (DFT) calculations have also verified that the incorporation of Fe and S optimizes the electrons redistribution and the d-band center, decreasing the energy barrier of the rate-determining step (*Oâ*OOH). Benefited from the unique electronic structure and intermediate adsorption, the Fe/S-NiOOH/NF catalyst only requires the overpotential of 345 mV to reach the industrial current density of 1000 mA cm-2 for 120 h. Meanwhile, assembled AEM water electrolyzer (Fe/S-NiOOH//Pt/C-60 °C) can deliver 1000 mA cm-2 at a cell voltage of 2.24 V, operating at the average energy efficiency of 71% for 100 h. In summary, this work presents a rapid self-reconstruction strategy for high-performance AEM electrocatalysts for future hydrogen economy.
ABSTRACT
The pit mud in the Baijiu fermentation cellar is an abundant microbial resource that is closely related to the quality of baijiu. However, many naturally existing species might be in a viable but nonculturable (VBNC) state, posing challenges to the isolation and application of functional species. Herein, a previously isolated strain from baijiu mash, Umezawaea beigongshangensis, was found to contain the rpf gene that encodes resuscitation promotion factor (Rpf). Therefore, the gene was cloned and heterologously expressed, and the recombinant protein (Ub-Rpf 2) was purified. Ub-Rpf 2 was found to significantly promote the growth of resuscitated VBNC state Corynebacterium beijingensis and Sphingomonas beigongshangensis. To determine the resuscitation effect of Ub-Rpf 2 on real ecological samples, the protein was supplemented in pit mud for enrichment culture. Results revealed that specific families and genera were enriched in abundance upon Ub-Rpf 2 incubation, including a new family of Symbiobacteraceae and culturable Symbiobacterium genus. Furthermore, 14 species belonging to 12 genera were obtained in Ub-Rpf 2 treated samples, including a suspected novel species. This study lays a foundation for applying Rpf from U. beigongshangensis to exploit microbial resources in baijiu pit mud.
Subject(s)
Actinomycetales , Lactobacillales , Bacteria/genetics , Actinomycetales/metabolism , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Fermentation , Lactobacillales/metabolismABSTRACT
A Gram-stain-positive actinomycete, designated REN17T, was isolated from fermented grains of Baijiu collected from Sichuan, PR China. It exhibited branched substrate mycelia and a sparse aerial mycelium. The optimal growth conditions for REN17T were determined to be 28â°C and pH 7, with a NaCl concentration of 0â% (w/v). ll-Diaminopimelic acid was the diagnostic amino acid of the cell-wall peptidoglycan and the polar lipids were composed of phosphatidylethanolamine, phosphatidylinositol, an unidentified phospholipid, two unidentified lipids and four unidentified glycolipids. The predominant menaquinone was MK-9 (H2), MK-9 (H4), MK-9 (H6) and MK-9 (H8). The major fatty acids were iso-C16 : 0. The 16S rRNA sequence of REN17T was most closely related to those of Streptomyces apricus SUN 51T (99.8â%), Streptomyces liliiviolaceus BH-SS-21T (99.6â%) and Streptomyces umbirnus JCM 4521T (98.9â%). The digital DNA-DNA hybridization, average nucleotide identity and average amino acid identify values between REN17T and its closest replated strain, of S. apricus SUN 51T, were 35.9, 88.9 and 87.3â%, respectively. Therefore, REN17T represents a novel species within the genus Streptomyces, for which the name Streptomyces beigongshangae sp. nov. is proposed. The type strain is REN17T (=GDMCC 4.193T=JCM 34712T). While exploring the function of the strain, REN17T was found to possess the ability to transform major ginsenosides of Panax notoginseng (Burk.) F.H. Chen (Araliaceae) into minor ginsenoside through HPLC separation, which was due to the presence of ß-glucosidase. The recombinant ß-glucosidase was constructed and purified, which could produce minor ginsenosides of Rg3 and C-K. Finally, the enzymatic properties were characterized.
Subject(s)
Bacterial Typing Techniques , DNA, Bacterial , Fatty Acids , Fermentation , Ginsenosides , Nucleic Acid Hybridization , Panax notoginseng , Phylogeny , RNA, Ribosomal, 16S , Sequence Analysis, DNA , Streptomyces , Vitamin K 2 , RNA, Ribosomal, 16S/genetics , Fatty Acids/chemistry , Streptomyces/isolation & purification , Streptomyces/genetics , Streptomyces/classification , Vitamin K 2/analogs & derivatives , DNA, Bacterial/genetics , China , Panax notoginseng/microbiology , Ginsenosides/metabolism , Peptidoglycan , Edible Grain/microbiology , Diaminopimelic Acid , Phospholipids/chemistry , Base CompositionABSTRACT
The baijiu fermentation environment hosts a variety of micro-organisms, some of which still remain uncultured and uncharacterized. In this study, the isolation, cultivation and characterization of three novel aerobic bacterial strains are described. The cells of strain REN20T were Gram-negative, strictly aerobic, motile and grew at 26-37â°C, at pH 6.0-9.0 and in the presence of 0-5.0âââ% (w/v) NaCl. The cells of strain REN29T were Gram-negative, strictly aerobic, motile and grew at 15-30â°C, at pH 6.0-9.0 and in the presence of 0-10.0âââ% (w/v) NaCl. The cells of strain REN33T were Gram-positive, strictly aerobic, motile and grew at 15-37â°C, at pH 5.0-10.0 and in the presence of 0-7.0âââ% (w/v) NaCl. The digital DNA-DNA hybridization and average nucleotide identity by orthology values between type strains in related genera and REN20T (20.3-36.8â% and 79.8-89.9ââ%), REN29T (20.3-36.8ââ% and 74.5-88.5ââ%) and REN33T (22.6-48.6ââ% and 75.8-84.2ââ%) were below the standard cut-off criteria for the delineation of bacterial species, respectively. Based on polyphasic taxonomy analysis, we propose three new species, Bosea beijingensis sp. nov. (=REN20T=GDMCC 1.2894T=JCM 35118T), Telluria beijingensis sp. nov. (=REN29T=GDMCC 1.2896T=JCM 35119T) and Agrococcus beijingensis sp. nov. (=REN33T=GDMCC 1.2898T=JCM 35164T), which were recovered during cultivation and isolation from baijiu mash.
Subject(s)
Actinomycetales , Bradyrhizobiaceae , Oxalobacteraceae , Sodium Chloride , Phylogeny , Sequence Analysis, DNA , RNA, Ribosomal, 16S/genetics , DNA, Bacterial/genetics , Bacterial Typing Techniques , Base Composition , Fatty Acids/chemistry , Bacteria, AerobicABSTRACT
The hitherto unknown hexakis(halomethyl)-functionalized tribenzotriquinacenes (TBTQs) 9 and 10 were synthesized from the key 4b,8b,12b-tribromo-TBTQ derivative 6 by an improved route in 67% overall yield. Extension of the bowl-shaped framework of 9 or 10 by threefold condensation with propargylamine or 2-azidoethylamine afforded the corresponding TBTQ-trialkyne 11 and TBTQ-triazide 12, respectively. While attempts to construct bis-TBTQ cages, including homodimerization of 11 and heterocoupling of 11 with 12, were unsuccessful, triazide 12 was found to undergo threefold [3 + 2]-cycloaddition with 3-ethynylaniline and phloroglucinol tripropargyl ether under click chemistry conditions. The latter reaction enabled facile capping of the TBTQ bowl to give the novel cage compound 5 in 22% yield.
ABSTRACT
OBJECTIVE: To construct chimeric antigen receptor (CAR)-T cells targeting epithelial cell adhesion molecule (EpCAM) antigen (anti-EpCAM-CAR-T). METHODS: A third-generation CAR-T cell construct used a single-chain variable fragment derived from monoclonal antibody against human EpCAM. Peripheral blood mononuclear cells were extracted from volunteers. The proportion of cluster of differentiation 8 positive (CD8+) and CD4 + T cells was measured using flow cytometry. Western blot was used to detect the expression of EpCAM-CAR. The killing efficiency was detected using the MTT assay and transwell assay, and the secretion of killer cytokines tumour necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) was detected using the ELISA. The inhibitory effect of EpCAM-CAR-T on colorectal cancer in vivo was detected using xenografts. RESULTS: It was found that T cells expanded greatly, and the proportion of CD3+, CD8 + and CD4 + T cells was more than 60%. Furthermore, EpCAM-CAR-T cells had a higher tumour inhibition rate in the EpCAM expression positive group than in the negative group (P < 0.05). The secretion of killer cytokines TNF-α and IFN-γ in the EpCAM expression positive cell group was higher than that in the negative group (P < 0.05). In the experimental group treated with EpCAM-CAR-T cells, the survival rate of nude mice was higher (P < 0.05), and the tumour was smaller than that in the blank and control groups (P < 0.05). The secretion of serum killer cytokines TNF-α and IFN-γ in tumour-bearing nude mice in the experimental group treated with EpCAM-CAR-T cells was higher than that in the blank and control groups (P < 0.05). CONCLUSION: This study successfully constructed EpCAM-CAR cells and found that they can target and recognise EpCAM-positive tumour cells, secrete killer cytokines TNF-α and IFN-γ and better inhibit the growth and metastasis of colorectal cancer in vitro and in vivo than unmodified T cells.
Subject(s)
Colorectal Neoplasms , Epithelial Cell Adhesion Molecule , Immunotherapy, Adoptive , Receptors, Chimeric Antigen , Epithelial Cell Adhesion Molecule/immunology , Epithelial Cell Adhesion Molecule/metabolism , Colorectal Neoplasms/immunology , Colorectal Neoplasms/therapy , Humans , Animals , Receptors, Chimeric Antigen/immunology , Immunotherapy, Adoptive/methods , Mice , Tumor Necrosis Factor-alpha/metabolism , Xenograft Model Antitumor Assays , Interferon-gamma/metabolism , Cell Line, Tumor , Female , Mice, Nude , CD8-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/immunologyABSTRACT
Tetrandrine (TET) possesses multiple pharmacological activities and could suppress tumor proliferation via PI3K pathway inhibition. However, inferior antitumor activity and potential toxicity limit its clinical application. In the present study, a series of 14-sulfonamide and sulfonate TET derivatives were designed, synthesized, and evaluated for biological activities. Through structural-activity relationship studies, compound 3c with α, ß-unsaturated carbonyl group exhibited the most potent activity against all tested tumor cell lines (including Hela, HCT116, HepG2, MCF-7, and SHSY5Y), as well as negligible toxicity against normal cell lines LO2 and HEK293. Additionally, compound 3c effectively inhibited HCT116 and CT26 cell proliferation in vitro with increased cell proportion in the G2/M phase, activated the mitochondrial apoptosis pathway, and induced colon cancer cell apoptosis by suppressing the PI3K/AKT/mTOR pathway. The further molecular docking results confirmed that compound 3c is potentially bound to multiple residues in PI3K with a stronger binding affinity than TET. Ultimately, compound 3c dramatically suppressed tumor growth in the CT26 xenograft tumor model, without noticeable visceral toxicity detected in the high-dose group. In summary, compound 3c might present new insights for designing new PI3K inhibitors and be a potential candidate for colon cancer treatment.
Subject(s)
Benzylisoquinolines , Colonic Neoplasms , Proto-Oncogene Proteins c-akt , Humans , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction , Phosphatidylinositol 3-Kinases/metabolism , Molecular Docking Simulation , HEK293 Cells , TOR Serine-Threonine Kinases/metabolism , Cell Line, Tumor , Apoptosis , Cell Proliferation , Colonic Neoplasms/drug therapy , Colonic Neoplasms/metabolismABSTRACT
The contraction of heart cells is controlled by the intermolecular signaling between L-type Ca2+ channels (LCCs) and ryanodine receptors (RyRs), and the nanodistance between them depends on the interaction between junctophilin-2 (JPH2) in the sarcoplasmic reticulum (SR) and caveolin-3 (CAV3) in the transversal tubule (TT). In heart failure, decreased expression of JPH2 compromises LCC-RyR communication leading to deficient blood-pumping power. In the present study, we found that JPH2 and CAV3 transcription was concurrently regulated by serum response factor (SRF) and myocardin. In cardiomyocytes from torpid ground squirrels, compared with those from euthermic counterparts, myocardin expression was up-regulated, which boosted both JPH2 and CAV3 expression. Transmission electron microscopic imaging showed that the physical coupling between TTs and SRs was tightened during hibernation and after myocardin overexpression. Confocal Ca2+ imaging under the whole-cell patch clamp condition revealed that these changes enhanced the efficiency of LCC-RyR intermolecular signaling and fully compensated the adaptive down-regulation of LCCs, maintaining the power of heart contraction while avoiding the risk of calcium overload during hibernation. Our finding not only revealed an essential molecular mechanism underlying the survival of hibernating mammals, but also demonstrated a "reverse model of heart failure" at the molecular level, suggesting a strategy for treating heart diseases.
Subject(s)
Calcium Signaling , Hibernation , Myocytes, Cardiac/metabolism , Animals , Caveolins/genetics , Caveolins/metabolism , Cells, Cultured , Excitation Contraction Coupling , Membrane Proteins/genetics , Membrane Proteins/metabolism , Nuclear Proteins/blood , Nuclear Proteins/metabolism , Sciuridae , Trans-Activators/blood , Trans-Activators/metabolismABSTRACT
BACKGROUND: Systemic infections are associated with the development of AD, especially in individuals carrying the APOE4 genotype. However, the detailed mechanism through which APOE4 affects microglia inflammatory response remains unclear. METHODS: We obtained human snRNA-seq data from the Synapse AD Knowledge Portal and assessed the DEGs between APOE3 and APOE4 isoforms in microglia. To verify the interaction between ApoE and infectious products, we used ApoE to stimulate in vitro and in vivo models in the presence or absence of LPS (or ATP). The NLRP3 gene knockout experiment was performed to demonstrate whether the APOE-NLRP3 axis was indispensable for microglia to regulate inflammation and mitochondrial autophagy. Results were evaluated by biochemical analyses and fluorescence imaging. RESULTS: Compared with APOE3, up-regulated genes in APOE4 gene carriers were involved in pro-inflammatory responses. ApoE4-stimulation significantly increased the levels of NLRP3 inflammasomes and ROS in microglia. Moreover, compared with ApoE4 alone, the co-incubation of ApoE4 with LPS (or ATP) markedly promoted pyroptosis. Both NF-κB activation and mitochondrial autophagy dysfunction were contributed by the increased level of NLRP3 inflammasomes induced by ApoE4. Furthermore, the pathological impairment induced by ApoE4 could be reversed by NLRP3 KO. CONCLUSIONS: Our study highlights the importance of NLRP3 inflammasomes in linking ApoE4 with microglia innate immune function. These findings not only provide a molecular basis for APOE4-mediated neuroinflammatory but also reveal the potential reason for the increased risk of AD in APOE4 gene carriers after contracting infectious diseases.
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OBJECTIVE: Imnovid® is an immunomodulatory drug with antineoplastic activity. The aim of this study was to evaluate the bioequivalence and safety of the generic drug pomalidomide (Chia Tai Tianqing Pharmaceutical Group Co., Ltd) and its originator product Imnovid® (Celgene Europe Ltd) in the fasting and fed states, respectively. METHODS: The research consisted of two parts: one with a dose of 1 mg and the other with a dose of 4 mg. 48 healthy subjects were included in each study and were divided into two groups (fasting group and fed group) at a 1:1 ratio to administrate study drugs orally. The plasma drug concentrations were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). RESULTS: The 90% CI of GMR for main pharmacokinetic (PK) parameters (Cmax, AUC0 - t and AUC0-∞) met the requirements of bioequivalence standards. The incidence and severity of AEs associated with pomalidomide and Imnovid® were similar. CONCLUSION: The results proved the PK parameters of pomalidomide and Imnovid® were similar and bioequivalent. Both drugs showed safety profile well.
Subject(s)
Thalidomide , Therapeutic Equivalency , Humans , Area Under Curve , Capsules , Chromatography, Liquid , Cross-Over Studies , East Asian People , Fasting , Healthy Volunteers , Tablets , Tandem Mass Spectrometry , Thalidomide/analogs & derivatives , Thalidomide/pharmacokineticsABSTRACT
Growing evidence suggests the involvement of the microbiota-gut-brain axis in cognitive impairment induced by sleep deprivation (SD), however how the microbiota-gut-brain axis work remains elusive. Here, we discovered that chronic SD induced intestinal dysbiosis, activated NLRP3 inflammasome in the colon and brain, destructed intestinal/blood-brain barrier, and impaired cognitive function in mice. Transplantation of "SD microbiota" could almost mimic the pathological and behavioral changes caused by chronic SD. Furthermore, all the behavioral and pathological abnormalities were practically reversed in chronic sleep-deprived NLRP3-/- mice. Regional knockdown NLRP3 expression in the gut and hippocampus, respectively. We observed that down-regulation of NLRP3 in the hippocampus inhibited neuroinflammation, and ameliorated synaptic dysfunction and cognitive impairment induced by chronic SD. More intriguingly, the down-regulation of NLRP3 in the gut protected the intestinal barrier, attenuated the levels of peripheral inflammatory factors, down-regulated the expression of NLRP3 in the brain, and improved cognitive function in chronic SD mice. Our results identified gut microbiota as a driver in chronic SD and highlighted the NLRP3 inflammasome as a key regulator within the microbiota-gut-brain axis.
Subject(s)
Cognitive Dysfunction , Inflammasomes , Mice , Animals , Inflammasomes/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Sleep Deprivation/complications , Dysbiosis/chemically induced , Hippocampus/metabolism , Cognitive Dysfunction/metabolism , IntestinesABSTRACT
Polycyclic aromatic hydrocarbons (PAHs) are widely present in the environment as toxic pollutants. In this study, quantum chemistry methods are used to study reactions of PAHs in both particle and gas phases. Seven theoretical methods are exploited to predict the reactive sites of 15 PAHs in the particle phase. Among these methods, the performance of the condensed Fukui function (CFF) is optimum. The gas-phase reactions of eight PAHs are also investigated. Except for fluorene, CFF predicts correctly the gas-phase mono-nitro products for seven systems. The products of fluorene predicted by CFF are 1-nitrofluorene and 3-nitrofluorene, which is however inconsistent with the experimental results. Transition state theory is then used to investigate the reaction mechanism of fluorene. Calculated rate constants for 3-nitrofluorene and 2-nitrofluorene formation are much bigger than that for 1-nitrofluorene formation, which is in agreement with the experimental results.
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AIM: To investigate the interplay of incident chronic kidney disease (CKD) and/or heart failure (HF) and their associations with prognosis in a large, population-based cohort with type 2 diabetes (T2DM). METHODS: Patients aged ≥18 years with new-onset T2DM, without renal disease or HF at baseline, were identified from the territory-wide Clinical Data Analysis Reporting System between 2000 and 2015. Patients were followed up until December 31, 2020 for incident CKD and/or HF and all-cause mortality. RESULTS: Among 102 488 patients (median age 66 years, 45.7% women, median follow-up 7.5 years), new-onset CKD occurred in 14 798 patients (14.4%), in whom 21.7% had HF. In contrast, among 9258 patients (9.0%) with new-onset HF, 34.6% had CKD. The median time from baseline to incident CKD or HF (4.4 vs. 4.1 years) did not differ. However, the median (interquartile range) time until incident HF after CKD diagnosis was 1.7 (0.5-3.6) years and was 1.2 (0.2-3.4) years for incident CKD after HF diagnosis (P < 0.001). The crude incidence of CKD was higher than that of HF: 17.6 (95% confidence interval [CI] 17.3-17.9) vs. 10.6 (95% CI 10.4-10.9)/1000 person-years, respectively, but incident HF was associated with a higher adjusted-mortality than incident CKD. The presence of either condition (vs. CKD/HF-free status) was associated with a three-fold hazard of death, whereas concomitant HF and CKD conferred a six to seven-fold adjusted hazard of mortality. CONCLUSION: Cardiorenal complications are common and are associated with high mortality risk among patients with new-onset T2DM. Close surveillance of these dual complications is crucial to reduce the burden of disease.
Subject(s)
Diabetes Mellitus, Type 2 , Heart Failure , Kidney Failure, Chronic , Renal Insufficiency, Chronic , Humans , Female , Adolescent , Adult , Aged , Male , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/epidemiology , Heart Failure/complications , Heart Failure/epidemiology , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/epidemiology , Kidney Failure, Chronic/complications , Prognosis , Risk FactorsABSTRACT
Atractylenolide I (Atr-I) was found to sensitize a variety of human cancer cells in previous studies. Purinergic P2X7R plays important role in different cancers. However, whether Atr-I could generate antitumor activity in human cervical cancer cells and P2X7R get involved in this effect remain unclear. In this study, Hela (HPV 18 +) and SiHa (HPV 16 +) cells were treated with different doses of Atr-I. The results indicated that agonist and antagonist of P2X7 receptors, BzATP and JNJ-47965567 (JNJ), could suppress the proliferation of Hela and SiHa cells. Atr-I demonstrated a considerable antitumor effect in both human cervical cancer cells in vitro. Atr-I combined with P2X7R agonist, BzATP, restored Atr-I-induced growth inhibition in Hela cells but not in SiHa cells. However, the combinatorial treatment of P2X7R antagonist JNJ and Atr-I has an additive effect on cell growth inhibition in SiHa cells rather than in Hela cells. It implied that P2X7R would get involved in the anti-human cervical cancer cells effect of Atr-I.
Subject(s)
Receptors, Purinergic P2X7 , Uterine Cervical Neoplasms , Female , Humans , Cell Proliferation , HeLa Cells , Purinergic P2X Receptor Antagonists/pharmacology , Antineoplastic Agents/therapeutic useABSTRACT
Hg-based chalcogenides possess diverse structures, large nonlinear-optical (NLO) responses, and suitable birefringences, making them potentially suitable for numerous crucial criteria of practical application as infrared (IR) NLO crystals. Here, a new pentanary Hg-based sulfide K2Ba7HgIn4S16 has been discovered by a high-temperature solid-state method. It crystallizes in the orthorhombic P21212 space group, and its one-dimensional structure is constructed by {[In2S7]8-}∞ chains and isolated [HgS4]6- planar quadrilateral units located bewteeen the chains, representing a novel type of chalcogenide. K2Ba7HgIn4S16 exhibits a moderate NLO effect of 0.5 × AGS at 2.1 µm and a high laser-induced damage threshold of â¼5.8 × AGS, as well as a band gap of 2.98 eV, demonstrating that K2Ba7HgIn4S16 is a potential IR NLO material. This work enriches the structural chemistry of chalcogenides and the family of Hg-based IR NLO chalcogenides.
ABSTRACT
Objective: Hemostatic gauze application is an effective way to control major bleeding, which is the most common cause of death in trauma in both civilian and military settings. Coagulation derangement after acute exposure to high altitude might alter the effects of hemostatic gauzes. The present study aimed to observe the hemostatic effects of bio-zeolite gauze (BZG) and QuikClot Combat Gauze® (QCG) on major bleeding in rabbits acutely exposed to high altitude.Methods: Sixty rabbits were randomly and evenly divided into six groups. Animal models of simulated blast- and fragment-induced inguinal major bleeding were prepared in lower altitude and high-altitude areas, and BZG, QCG, and ordinary gauze without hemostatic material were used to control bleeding. The primary outcomes included immediate hemostasis rate, blood loss, and survival rate, while the secondary outcomes included hemodynamic parameters, laboratory examinations, and coagulation-relevant markers.Results: The overall effects of BZG and QCG were better than those of ordinary gauze, with a higher immediate hemostatic rate, less blood loss, and higher survival rate at 90 min after gauze application and higher red blood cell and platelet counts and lower creatinine level at 30 min after gauze application in lower altitude. The concentrations of coagulation factor XII and factor X in rabbits acutely exposed to high altitude were significantly lower than those in lower altitude. At high altitude, the hemostatic effects of BZG did not decrease significantly compared to those in the lower altitude, whereas those of ordinary gauze and QCG decreased significantly at high altitude compared to those in the lower altitude.Conclusions: Coagulation derangement after acute exposure to high altitude has negative effects on ordinary gauze and QCG but has no significant negative hemostatic effects on BZG.
Subject(s)
Emergency Medical Services , Hemostatics , Zeolites , Animals , Rabbits , Altitude , Hemorrhage/drug therapy , Hemostasis , Hemostatic Techniques , Hemostatics/pharmacologyABSTRACT
Brown fermented milk (BFM) is favored by consumers in the dairy market for its unique burnt flavor and brown color. However, Maillard reaction products (MRP) from high-temperature baking are also noteworthy. In this study, tea polyphenols (TP) were initially developed as potential inhibitors of MRP formation in BFM. The results showed that the flavor profile of BFM did not change after adding 0.08% (wt/wt) of TP, and its inhibition rates on 5-hydroxymethyl-2-furaldehyde (5-HMF), glyoxal (GO), methylglyoxal (MGO), Nε-carboxymethyl lysine (CML), and Nε-carboxyethyl lysine (CEL) were 60.8%, 27.12%, 23.44%, 57.7%, and 31.28%, respectively. After 21 d of storage, the levels of 5-HMF, GO, MGO, CML, and CEL in BFM with TP were 46.3%, 9.7%, 20.6%, 5.2%, and 24.7% lower than the control group, respectively. Moreover, a smaller change occurred in their color and the browning index was lower than that of the control group. The significance of this study was to develop TP as additives to inhibit the production of MRP in brown fermented yogurt without changing color and flavors, thereby making dairy products safer for consumers.
Subject(s)
Maillard Reaction , Milk , Animals , Milk/chemistry , Lysine/analysis , Polyphenols/analysis , Magnesium Oxide , Pyruvaldehyde/analysis , Glyoxal/analysis , Glycation End Products, Advanced/analysis , TeaABSTRACT
PURPOSE: To develop animal models of penetrating thoracic injuries and to observe the effects of the animal model-based training on improving the trainees' performance for emergent and urgent thoracic surgeries. METHODS: With a homemade machine, animal models of lung injuries and penetrating heart injuries were produced in porcine and used for training of chest tube drainage, urgent sternotomy, and emergent thoracotomy. Coefficient of variation of abbreviated injury scale and blood loss was calculated to judge the reproducibility of animal models. Five operation teams from basic-level hospitals (group A) and five operation teams from level III hospitals (group B) were included to be trained and tested. Testing standards for the operations were established after thorough literature review, and expert questionnaires were employed to evaluate the scientificity and feasibility of the testing standards. Tests were carried out after the training. Pre- and post-training performances were compared. Post-training survey using 7-point Likert scale was taken to evaluate the feelings of the trainees to these training approaches. RESULTS: Animal models of the three kinds of penetrating chest injuries were successfully established and the coefficient of variation of abbreviated injury scale and blood loss were all less than 25%. After literature review, testing standards were established, and expert questionnaire results showed that the scientific score was 7.30 ± 1.49, and the feasibility score was 7.50 ± 0.89. Post-training performance was significantly higher in both group A and group B than pre-training performance. Post-training survey showed that all the trainees felt confident in applying the operations and were generally agreed that the training procedure were very helpful in improving operation skills for thoracic penetrating injury. CONCLUSIONS: Animal model-based simulation training established in the current study could improve the trainees' performance for emergent and urgent thoracic surgeries, especially of the surgical teams from basic-level hospitals.
Subject(s)
Thoracic Injuries , Wounds, Penetrating , Animals , Swine , Reproducibility of Results , Wounds, Penetrating/surgery , Thoracotomy , Thoracic Injuries/surgery , Hemorrhage , Models, AnimalABSTRACT
River sediment is vital in containing water pollution and strengthening water remediation. This paper has conducted a study on the microecological health assessment of the sediment and water body of Guixi River in Dianjiang, Chongqing, China, using metagenomics sequencing and microbial biological integrity index (M-IBI) technology. The analysis of physical and chemical characteristics shows that the concentration of TN varies from 2.62 to 9.76 mg/L in each sampling section, and the eutrophication of the water body is relatively severe. The proportion of Cyanobacteria in the sampling section at the sink entrance is higher than that of other sites, where there are outbreaks of water blooms and potential hazards to human health. The dominant functions of each site include carbon metabolism, TCA cycle, and pyruvate metabolism. In addition, the main virulence factors and antibiotic resistance genes in sediment are Type IV pili (VF0082), LOS (CVF494), MymA operon (CVF649), and macrolide resistance genes macB, tetracyclic tetA (58), and novA. Correlation analysis of environmental factors and microorganisms was also performed, and it was discovered that Thiothrix and Acidovorax had obvious gene expression in the nitrogen metabolism pathway, and the Guixi River Basin had a self-purification capacity. Finally, based on the microecological composition of sediment and physical and chemical characteristics of the water body, the health assessment was carried out, indicating that the main pollution area was Dianjiang Middle School and the watershed near the sewage treatment plant. The findings should theoretically support an in-depth assessment of the water environment's microecological health.