Distinguishable short-term effects of tea and water drinking on human saliva redox.

Food consumption can alter the biochemistry and redox status of human saliva, and the serving temperature of food may also play a role. The study aimed to explore the immediate (3 min) and delayed (30 min) effects of hot tea (57 ± 0.5 °C) ingestion and cold tea (8 ± 0.5 °C) ingestion on the salivary flow rate and salivary redox-relevant attributes. The saliva was collected from 20 healthy adults before, 3-min after and 30-min after the tea ingestion. The hot or cold deionised water at the same temperatures were used as control. The salivary flow rate and redox markers in hot tea (HBT), cold tea (CBT), hot water (HW) and cold water (CW) group were analysed and compared. The results demonstrated that neither the black tea nor the water altered the salivary flow rate; the black tea immediately increased the salivary thiol (SH) and malondialdehyde (MDA) content while reduced salivary uric acid (UA) significantly. The tea ingestion showed a tendency to elevate the ferric reducing antioxidant power (FRAP) in saliva, although not significantly. The water ingestion decreased the MDA content immediately and increased the UA level significantly. Cold water was found to induce a greater delayed increase in total salivary total protein (TPC) than the hot water. In conclusion, the black tea ingestion affects the redox attributes of human saliva acutely and significantly, while the temperature of drink makes the secondary contribution.

A novel iridium(III) complex-based ratiometric luminescence probe for monitoring hydrogen sulfide in living cells and zebrafish.

Hydrogen sulfide exhibits crucial functions in many biological and physiological processes. The abnormal levels of H2S have been revealed to be associated with numerous human diseases. The majority of existing fluorescent probes toward H2S may still need to be improved in terms of single output signal, water solubility, biotoxicity and photostability. The construction of a ratiometric fluorescent probe based on metal complex is one effective strategy for avoiding the mentioned problems for precisely detecting H2S. Herein, we report an iridium(III) complex-based ratiometric luminescence probe (Ir-PNBD), which is designed by coupling the 7-nitro-2,1,3-benzoxadiazoles (NBD) to one of the bipyridine ligands of Ir (III) complex luminophore through a piperazition moiety. Ir-PNBD owns high selectivity and sensitivity toward H2S, and an excellent ability to target mitochondria. Moreover, Ir-PNBD was further successfully utilized to visualize exogenous and endogenous H2S in HeLa cells and zebrafish. Our work offers new opportunities to gain deeper insights into the construction of transition metal complex-based ratiometric luminescent probes and expands their applications in biomedical imaging and disease diagnosis.

The impact of inflammatory biomarkers on amputation rates in patients with diabetic foot ulcers.

Diabetic Foot Ulcers (DFUs) are a major complication of diabetes, often leading to amputation. Understanding the relationship between haematological inflammatory markers and the incidence of amputation in DFU patients with infectious complications is crucial for improving management and outcomes. This retrospective study, conducted from May 2020 to October 2022, involved 109 patients with DFUs, categorised into amputation (AM) and non-amputation (NAM) groups. Patients were evaluated for various factors, including demographic data, DFU duration, and blood parameters such as haemoglobin A1c (HbA1c), haemoglobin (Hb), albumin (ALB), white blood cell count (WBC), erythrocyte sedimentation rate (ESR), procalcitonin (PCT), C-reactive protein (CRP), platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), and lymphocyte-to-monocyte ratio (LMR). Statistical analyses were performed using independent sample t-tests, Mann-Whitney U test and logistic regression. The univariate analysis showed no significant difference in BMI, DM duration or DFU duration between groups. However, significant differences were noted in PCT, Hb, ESR, ALB, HbA1c and WBC levels, and in inflammatory ratios (NLR, PLR and LMR). Multivariate logistic regression identified CRP, NLR and PLR as independent risk factors for amputation. The study highlights CRP, PLR and NLR as key independent risk factors for amputation in patients with DFUs. These easily obtainable markers from routine blood tests can effectively aid in predicting the risk of osteomyelitis and amputation, enhancing clinical decision making and patient care strategies.

Integration of photothermal water evaporation with photocatalytic microplastics upcycling via nanofluidic thermal management.

Photothermal heating and photocatalytic treatment are two solar-driven water processing approaches by harnessing NIR and UV-vis light, respectively, which can fully utilize solar energy if integrated. However, it remains a challenge to achieve high performance in both approaches when integrated in a material due to uncontrollable heat diffusion. Here, we report a demonstration of heat confinement on photothermal sites and fluid cooling on photocatalysis sites at the nanoscale, within a well-designed heat and fluid confinement nanofiber reactor. Photothermal and photocatalytic nanostructures were alternatively aligned in electrospun nanofibers for on-demand nanofluidic thermal management as well as easy folding into 3D structures with enhanced light utilization and mass transfer. Such a design showed simultaneously high photothermal evaporation rate (2.59 kg m-2 h-1, exceeding the limit rate) and efficient photocatalytic upcycling of microplastics pollutant into valued products. Enabled by controlled photothermal heating, the valued main product (i.e., methyl acetate) can be evaporated out with 100% selectivity by in situ separation.

The short-term outcome of intracranial stenosis with distal thrombosis treated with balloon-assisted tracking.

Background and purposes: Treating intracranial stenosis with distal thrombosis (IS&DT) using traditional mechanical thrombectomy (MT) techniques has proven challenging. This study aimed to summarize the experience of utilizing the balloon-assisted tracking (BAT) technique for IS&DT. Methods: Demographic and morphologic characteristics of patients with IS&DT were collected for this study. The BAT technique, involving a half-deflated balloon outside the intermediate catheter tip, was used in all patients to navigate through the proximal stenosis. Various parameters were recorded, including the sequence of vascular reperfusion, the puncture-to-reperfusion time (PRT), the residual stenosis rate, and the occurrence of re-occlusion. The thrombolysis in cerebral infarction (TICI) scale was used to assess the reperfusion of intracranial vessels, with a TICI score of ≥2b considered as successful perfusion. The clinical status of patients was evaluated at three time points: pre-procedure, post-procedure, and at discharge using the modified Rankin score (mRS). Results: In this study, a total of 10 patients were diagnosed with IS&DT, consisting of 9 male patients (90.0%) and 1 female patient (10.0%). The patients' mean age was 63.10 years (ranging from 29 to 79 years). The mean National Institute of Health Stroke Scale (NIHSS) score before treatment was 24.3 (ranging from 12 to 40), indicating the severity of their condition. Following the procedure, all patients achieved successful reperfusion with a thrombolysis in cerebral infarction (TICI) score of ≥2b. The average puncture-to-reperfusion time (PRT) was 51.8 min (ranging from 25 to 100 min), indicating the time taken for the procedure. During the perioperative period, three patients (30.0%) experienced complications. One patient had hemorrhage, while two patients had contrast extravasation. Among these cases, only the patient with hemorrhage (10%) suffered from a permanent neurological function deficit. At discharge, the patient's condition showed improvement. The mean NIHSS score decreased to 13.2 (ranging from 1 to 34), indicating a positive response to treatment. The mean mRS score at discharge was 3.2 (ranging from 1 to 5), showing some level of functional improvement. Conclusion: In conclusion, the use of the balloon-assisted tracking (BAT) technique for treating intracranial stenosis with distal thrombosis (IS&DT) showed promising results. However, a moderate rate of perioperative complications was observed, warranting further investigation and refinement of the procedure.

Quantitative Assessment of Hemodynamics Associated With Embolization Degree in Brain Arteriovenous Malformations.

BACKGROUND AND OBJECTIVES: Grading systems, including the novel brain arteriovenous malformation endovascular grading scale (NBAVMES) and arteriovenous malformation embocure score (AVMES), predict embolization outcomes based on arteriovenous malformation (AVM) morphological features. The influence of hemodynamics on embolization outcomes remains unexplored. In this study, we investigated the relationship between hemodynamics and embolization outcomes. METHODS: We conducted a retrospective study of 99 consecutive patients who underwent transarterial embolization at our institution between 2012 and 2018. Hemodynamic features of AVMs were derived from pre-embolization digital subtraction angiography sequences using quantitative digital subtraction angiography. Multivariate logistic regression analysis was performed to determine the significant factors associated with embolization outcomes. RESULTS: Complete embolization (CE) was achieved in 17 (17.2%) patients, and near-complete embolization was achieved in 18 (18.2%) patients. A slower transnidal relative velocity (TRV, odds ratio [OR] = 0.71, P = .002) was significantly associated with CE. Moreover, higher stasis index of the drainage vein (OR = 16.53, P = .023), shorter transnidal time (OR = 0.15, P = .013), and slower TRV (OR = 0.9, P = .049) were significantly associated with complete or near-complete embolization (C/nCE). The area under the receiver operating characteristic curve for predicting CE was 0.87 for TRV, 0.72 for NBAVMES scores (ρ = 0.287, P = .004), and 0.76 for AVMES scores. The area under the receiver operating characteristic curve for predicting C/nCE was 0.77 for TRV, 0.61 for NBAVMES scores, and 0.75 for AVMES scores. Significant Spearman correlation was observed between TRV and NBAVMES scores and AVMES scores (ρ = 0.512, P < .001). CONCLUSION: Preoperative hemodynamic factors have the potential to predict the outcomes of AVM embolization. A higher stasis index of the drainage vein, slower TRV, and shorter transnidal time may indicate a moderate blood flow status or favorable AVM characteristics that can potentially facilitate embolization.

Associations between Urinary Concentrations of Polycyclic Aromatic Hydrocarbons and Overactive Bladder in US Adults: Data from the National Health and Nutrition Examination Survey 2005-2016.

INTRODUCTION: Polycyclic aromatic hydrocarbons (PAHs) are a group of chemicals that can induce oxidative stress and related cytotoxicity. Whether urinary concentrations of PAHs have effects on overactive bladder (OAB) in the general population is still unclear. This study investigated the associations between urinary PAHs and OAB. METHODS: 7,146 adults aged over 20 who participated in the US National Health and Nutrition Examination Survey 2005-2016 were studied. The impact of the six PAHs on OAB was evaluated by multivariate logistic regression, and percent changes related to different quartiles of those six PAH levels were calculated. Confounders including age, logarithmic urinary creatinine, gender, race, body mass index, educational level, marriage, poverty income ratio, diabetes, hypertension, and metabolic syndrome were controlled. RESULTS: There is a significant positive correlation between urinary concentrations of the six PAHs we include in the study and the occurrence of OAB. Furthermore, individuals with higher PAH levels also reported a more severe OAB symptom score (OABSS). CONCLUSIONS: Our findings revealed that adult men in the USA with higher urinary PAHs had a higher risk of OAB incidence. These findings suggest the importance of strong environmental regulation of PAHs to protect population health. However, the underlying mechanisms still need further exploration.

Hydroxyl-rich ferrofluid for efficient liquid phase microextraction of cinnamic acid derivatives in traditional Chinese medicine.

In this study, a hydroxyl-rich ferrofluid was prepared by dispersing silica-coated magnetic nanoparticles into a methyltrioctylammonium chloride-glycerol deep eutectic solvent and then employed in the preconcentration of trace-level of cinnamic acid derivatives (caffeic acid, p-hydroxycinnamic acid, ferulic acid, and cinnamic acid) in traditional Chinese medicine prior to high-performance liquid chromatography analysis. The structures of the synthesized materials were characterized by X-ray diffraction and infrared spectroscopy. The experimental parameters affecting the extraction performance, such as deep eutectic solvent composition, dosage of ferrofluid, pH of aqueous sample solution, salt concentration, extraction time, type, and volume of desorption solvent, were studied and optimized. Under the optimum conditions, the enrichment factors of four cinnamic acid derivatives were in the range of 107-114. Low detection limits (0.2-0.9 ng/mL), good precisions (relative standard deviations 1.2%-9.5%), and satisfactory recoveries (96.0%-104.7%) were achieved. Subsequently, the possible microextraction mechanism of the proposed method was explored and elucidated. It showed that the prepared ferrofluid is easily dispersed in the aqueous sample and achieved recovery after the extraction. The developed approach is a simple, convenient, and efficient method for preconcentration and determination of cinnamic acid derivatives in complex matrices.

Molten salt synthesis of 1T/2H mixed phase MoS2 for boosting photocatalytic H2 evolution via Schottky junction under EY-sensitized system.

Clean H2 fuel obtained from the photocatalytic water splitting to hydrogen reaction could efficiently alleviate current energy crisis and the concomitant environmental pollution problems. Therefore, it is desirable to search for a highly efficient photocatalytic system to decrease the energy barrier of water splitting reaction. Herein, the 1T/2H mixed phase MoS2 sample with Schottky junction between contact interfaces is developed through molten salt synthesis for photocatalytic hydrogen production under a dye-sensitized system (Eosin Y-TEOA-MoS2) driven by the visible light. In mixed phase MoS2 sample, the photogenerated electrons of 2H-phase MoS2 migrated to the 1T-phase MoS2 are difficult to jump back because of the existence of Schottky barrier, which greatly suppresses the quenching of EY and therefore results in an enhanced hydrogen evolution performance. Therefore, the optimized MoS2 sample (MoS2-350) has an initial hydrogen evolution rate of 213 µmol h-1 and corresponding apparent quantum yield of 36.1 % at 420 nm, far higher than those of pure Eosin Y. It is strongly confirmed by the steady-state/time-resolved photoluminescence (PL) spectra and transient photocurrent response experiments. With the assistance of Density functional theory (DFT) calculation, the function of Schottky junction in photocatalytic hydrogen evolution reaction is well explained. In addition, a new and universal method (SVM curve) of judging oxidation or reduction quenching for photosensitizers is proposed.

Intelligent responsive copper-diethyldithiocarbamate-based multifunctional nanomedicine for photothermal-augmented synergistic cancer therapy.

The design of multifunctional nanomedicine through the combination of multimodal treatments to achieve the optimal antitumor effect is essential for cancer therapy. Herein, we design and develop a multifunctional theranostic nanoplatform using an iron ion-doxorubicin (DOX) nanoscale coordination polymer (Fe/DOX NCP) as a shell coating on the surface of polyvinyl pyrrolidone (PVP) stabilized copper-diethyldithiocarbamate nanoparticles (Cu(DDC)2 NPs) for combined tumor chemo-/photothermal/chemodynamic therapy. The obtained Cu(DDC)2@Fe/DOX NPs display pH/laser dual-responsive degradation behavior and also exhibit favorable photothermal performance. Under 808 nm laser irradiation, Cu(DDC)2@Fe/DOX NPs can convert light into heat, which not only kills tumor cells via hyperthermia in photothermal therapy (PTT), but also accelerates the degradation of Fe/DOX NCPs to release Fe3+ and DOX. The liberated Fe3+ can be used to catalyze hydrogen peroxide via the Fenton reaction to produce highly toxic hydroxyl radicals (˙OH) in chemodynamic therapy (CDT). The released DOX and the exposed Cu(DDC)2 can cause significant cell death in combined chemotherapy via a superimposed effect. In vitro and in vivo results prove that Cu(DDC)2@Fe/DOX NPs with laser irradiation present remarkable anticancer performances in hyperthermia-enhanced chemo-/CDT. Therefore, this study provides a new strategy for highly efficient synergistic cancer therapy.

Characterization of brain resilience in Alzheimer's disease using polygenic risk scores and further improvement by integrating mitochondria-associated loci.

INTRODUCTION: Identification of high-risk people for Alzheimer's disease (AD) is critical for prognosis and early management. Longitudinal epidemiologic studies have observed heterogeneity in the brain and cognitive aging. Brain resilience was described as above-expected cognitive function. The "resilience" framework has been shown to correlate with individual characteristics such as genetic factors and age. Besides, accumulative evidence has confirmed the association of mitochondria with the pathogenesis of AD. However, it is challenging to assess resilience through genetic metrics, in particular incorporating mitochondria-associated loci. OBJECTIVES: In this paper, we first demonstrated that polygenic risk scores (PRS) could characterize individuals' resilience levels. Then, we indicated that mitochondria-associated loci could improve the performance of PRSs, providing more reliable measurements for the prevention and diagnosis of AD. METHODS: The discovery (N = 1,550) and independent validation samples (N = 2,090) were used to construct nine types of PRSs containing mitochondria-related loci (PRSMT) from both biological and statistical aspects and combined them with known AD risk loci derived from genome-wide association studies (GWAS).Individuals' levels of brain resilience were comprehensively measured by linear regression models using eight pathological characteristics. RESULTS: It was found that PRSs could characterize brain resilience levels (e.g., Pearson correlation test Pmin = 7.96×10-9). Moreover, the performance of PRS models could be efficiently improved by incorporating a small number of mitochondria-related loci (e.g., Pearson correlation test P improved from 1.41×10-3 to 6.09×10-6). PRSs' ability to characterize brain resilience was validated. More importantly, by incorporating some mitochondria-related loci, the performance of PRSs in measuring brain resilience could be significantly improved. CONCLUSION: Our findings imply that mitochondria may play an important role in brain resilience, and targeting mitochondria may open a new door to AD prevention and therapy.

Fabrication and characterization of curcumin-loaded nanoparticles using licorice protein isolate from Radix Glycyrrhizae.

Licorice was widely used in food and herbal medicine. In its extract industry, a substantial amount of licorice protein was produced and discarded as waste. Herein, we extracted Licorice Protein Isolate (LPI) and explored its potential as a curcumin nanocarrier. Using a pH-driven method, we fabricated LPI-curcumin nanoparticles with diameters ranging from 129.30 ± 3.21 nm to 75.03 ± 1.19 nm, depending on the LPI/curcumin molar ratio. The formation of LPI-curcumin nanoparticles was primarily driven by hydrophobic interactions, with curcumin entrapped in LPI being in an amorphous form. These nanoparticles significantly enhanced curcumin properties in terms of solubility, photochemical stability, and stability under varying pH, storage, and physiological conditions. Moreover, the loaded curcumin exhibited a 2.58-fold increase in cellular antioxidant activity on RAW 264.7 cells and a 1.86-fold increase in antitumor activity against HepG2 cells compared to its free form. These findings suggested that LPI could potentially serve as a promising novel delivery material.

Timing of microsurgical resection for ruptured brain arteriovenous malformations: a propensity score-matched analysis using prospective single-center registry data.

OBJECTIVE: The optimal microsurgical timing in ruptured brain arteriovenous malformations (AVMs) is not well understood and is surrounded by controversy. This study aimed to elucidate the impacts of microsurgical resection timing on clinical outcomes. METHODS: The authors retrieved and reviewed the records on all ruptured AVMs treated at their institution and registered in a nationwide multicenter prospective collaboration registry between August 2011 and August 2021. Patients were dichotomized into an early resection group (≤ 30 days from the last hemorrhagic stroke) and a delayed resection group (> 30 days after the last hemorrhagic stroke). Propensity score-matched analysis was used to compare long-term outcomes. The primary outcome was neurological status as assessed using the modified Rankin Scale (mRS). The secondary outcomes were complete obliteration rate, postoperative seizure, and postoperative hemorrhage. RESULTS: Of the 3649 consecutive AVMs treated at the authors' institution, a total of 558 ruptured AVMs were microsurgically resected and had long-term follow-up. After propensity score matching, 390 ruptured AVMs (195 pairs) were included in the comparison of outcomes. The mean (± standard deviation) clinical follow-up duration was 4.93 ± 2.94 years in the early resection group and 5.61 ± 2.56 years in the delayed resection group. Finally, as regards the distribution of mRS scores, short-term neurological outcomes were better in the delayed resection group (risk difference [RD] 0.3%, 95% CI -0.1% to 0.6%, p = 0.010), whereas long-term neurological outcomes were similar between the two groups (RD 0.0%, 95% CI -0.2% to 0.2%, p = 0.906). Long-term favorable neurological outcomes (early vs delayed: 90.8% vs 90.3%, p > 0.999; RD 0.5%, 95% CI -5.8% to 6.9%; RR 1.01, 95% CI 0.94-1.07) and long-term disability (9.2% vs 9.7%, p > 0.999; RD -0.5%, 95% CI -6.9% to 5.8%; RR 0.95, 95% CI 0.51-1.75) were also similar between these groups. In terms of secondary outcomes, postoperative seizure (early vs delayed: 8.7% vs 5.6%, p = 0.239; RD 3.1%, 95% CI -2.6% to 8.8%; RR 1.55, 95% CI 0.74-3.22), postoperative hemorrhage (1.0% vs 1.0%, p > 0.999; RD 0.0%, 95% CI -3.1% to 3.1%; RR 1.00, 95% CI 0.14-7.04), and hospitalization time (16.4 ± 8.5 vs 19.1 ± 7.9 days, p = 0.793) were similar between the two groups, whereas early resection had a lower complete obliteration rate (91.3% vs 99.0%, p = 0.001; RD -7.7%, 95% CI -12.9% to 3.1%; RR 0.92, 95% CI 0.88-0.97). CONCLUSIONS: Early and delayed resection of ruptured AVMs had similar long-term neurological outcomes. Delayed resection can lead to a higher complete obliteration rate, although the risk of rerupture during the resection waiting period should be vigilantly monitored.

Effect of alfalfa supplementary change dietary non-fibrous carbohydrate (NFC) to neutral detergent fiber (NDF) ratio on rumen fermentation and microbial function in Gansu alpine fine wool sheep (Ovis aries).

Bodyweight loss and rumen microbial dysfunction of grazing sheep was a challenge for the sheep production industry during cold season, which were considered to correlated with under-roughage-feeding. Alfalfa is a good roughage supplementary for ruminants, which can improve grazing sheep bodyweight-loss and rumen microbial dysfunction during grass-withering period. This study evaluated the effects of alfalfa hay supplementary change dietary non-fibrous carbohydrate/neutral detergent fiber (NFC/NDF) ratios on rumen fermentation and microbial function of Gansu alpine fine wool sheep during extreme cold season. 120 ewes (3-4 yrs) with an average body weight of 28.71 ± 1.22 kg were allocated randomly into three treatments, and fed NFC/NDF of 1.92 (H group), 1.11 (M group), and 0.68 (L group), respectively. This study was conducted for 107 d, including 7 d of adaption to the diets. The rumen fermentation parameters and microbial characteristics were measured after the end of feeding trials. The results showed that the concentrations of sheep body weight, nitrogen components (Total-N, Soluble protein-N and Ammonia-N), blood biochemical indices (LDH, BUN and CHO) and ruminal volatile fatty acids (TVFA and propionate) significantly increased with an increase in the proportion of NFC/NDF ratios (p < .05), and the acetate and acetate/propionat ratio presented a contrary decreasing trend (p < .05). A total of 1018 OTUs were obtained with 97% consistency. Ruminococcus, Ruminococcaceae and Prevotella were observed as the predominant phyla in ruminal fluid microbiota. Higher NFC/NDF ratios with Alfalfa supplementary increased the richness and diversity of ruminal fluid microbiota, and decreased ruminal fluid microbiota beta-diversity. Using clusters of orthologous groups (COG), the ruminal fluid microbiota of alfalfa supplementary feeding showed low immune pathway and high carbohydrate metabolism pathway. In summary, the study suggested that there was an increasing tendency in dietary NFC/NDF ratio of 1.92 in body weight, ruminal fermentation, microbial community composition and fermentation characteristics through developing alfalfa supplementary system.

Copper-Zinc-Doped Bilayer Bioactive Glasses Loaded Hydrogel with Spatiotemporal Immunomodulation Supports MRSA-Infected Wound Healing.

Developing biomaterials with antimicrobial and wound-healing activities for the treatment of wound infections remains challenging. Macrophages play non-negligible roles in healing infection-related wounds. In this study, a new sequential immunomodulatory approach is proposed to promote effective and rapid wound healing using a novel hybrid hydrogel dressing based on the immune characteristics of bacteria-associated wounds. The hydrogel dressing substrate is derived from a porcine dermal extracellular matrix (PADM) and loaded with a new class of bioactive glass nanoparticles (BGns) doped with copper (Cu) and zinc (Zn) ions (Cu-Zn BGns). This hybrid hydrogel demonstrates a controlled release of Cu2+ and Zn2+ and sequentially regulates the phenotypic transition of macrophages from M1 to M2 by alternately activating nucleotide-binding oligomerization domain (NOD) and inhibiting mitogen-activated protein kinases (MAPK) signaling pathways. Additionally, its dual-temporal bidirectional immunomodulatory function facilitates enhanced antibacterial activity and wound healing. Hence, this novel hydrogel is capable of safely and efficiently accelerating wound healing during infections. As such, the design strategy provides a new direction for exploring novel immunomodulatory biomaterials to address current clinical challenges related to the treatment of wound infections.

Sinularin stabilizes FOXO3 protein to trigger prostate cancer cell intrinsic apoptosis.

Sinularin, a natural product that purified from soft coral, exhibits anti-tumor effects against various human cancers. However, the mechanisms are not well understood. In this study, we demonstrated that Sinularin inhibited the viability of human prostate cancer cells in a dose-dependent manner and displayed significant cytotoxicity only at high concentration against normal prostate epithelial cell RWPE-1. Flow cytometry assay demonstrated that Sinularin induced tumor cell apoptosis. Further investigations revealed that Sinularin exerted anti-tumor activity through intrinsic apoptotic pathway along with up-regulation of pro-apoptotic protein Bax and PUMA, inhibition of anti-apoptotic protein Bcl-2, mitochondrial membrane potential collapses, and release of mitochondrial proteins. Furthermore, we illustrated that Sinularin induced cell apoptosis via up-regulating PUMA through inhibition of FOXO3 degradation by the ubiquitin-proteasome pathway. To explore how Sinularin suppress FOXO3 ubiquitin-proteasome degradation, we tested two important protein kinases AKT and ERK that regulate FOXO3 stabilization. The results revealed that Sinularin stabilized and up-regulated FOXO3 via inhibition of AKT- and ERK1/2-mediated FOXO3 phosphorylation and subsequent ubiquitin-proteasome degradation. Our findings illustrated the potential mechanisms by which Sinularin induced cell apoptosis and Sinularin may be applied as a therapeutic agent for human prostate cancer.

[Remediation of Three Oxidants on Polycyclic Aromatic Hydrocarbons in Coking Contaminated Soil and Its Response to Indigenous Microorganisms].

To explore the influences of chemical oxidation on the physiological and ecological functions of indigenous microorganisms during contaminated soil remediation, three oxidants, including KMnO4, Na2S2O8, and O3, were selected to investigate their remediation effects on PAHs and the responses to indigenous microorganisms under different liquid-solid ratios, in this study. The results showed that:when the ΣPAHs concentration was 679.1 mg·kg-1 and the dosage of KMnO4 and Na2S2O8 was 1%, the removal efficiency of ΣPAHs reached up to 96.9% and 95.7% under the liquid-solid ratio of 6:1; for the O3 treatment, the removal efficiency of ΣPAHs was the highest(82.3%) at the O3 dosage and the liquid-solid ratio of 72 mg·min-1 and 8:1, respectively. The removal efficiency of low ring(3-4 rings) PAHs was higher than that of high ring(5-6 rings) PAHs under different liquid-solid ratios. The highest removal efficiencies were observed for phenanthrene and acenaphthene, whereas for benzo[a]pyrene, only the KMnO4treatment provided an effective performance, showing the highest removal efficiency of 97.4%. The microbial quantity analysis indicated that the quantity of soil microorganisms in the soil dropped sharply after being treated with KMnO4, decreasing from 108 copies·g-1 to 105 copies·g-1, whereas it changed only slightly after being treated with Na2S2O8 and O3. The community structure analysis showed that Proteobacteria were predominant in the contaminated soil, with the relative abundance of 99.5%. The addition of KMnO4 and Na2S2O8 significantly increased the microbial diversity; in particular, the relative abundance of a variety of microorganisms(such as Ralstonia and Acinetobacter) that can degrade PAHs was remarkably increased. The analysis of microbial metabolic function pathways revealed that chemical oxidation could simultaneously increase the relative abundance of PAHs-degrading bacteria and improve the ability of organic metabolism. Overall, the KMnO4 treatment greatly altered the quantity of microorganisms and the structure of the microbial community and the relative abundance of PAHs-degrading microorganisms at the liquid-solid ratio of 6:1.