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In order to create a cost-effective Zr alloy with superior overall characteristics, Zr-xFe (x = 0, 2, 4, 6, 8, 10 at.%) binary alloys were prepared by a vacuum arc furnace system. The microstructure of these alloys was examined utilizing various techniques such as optical microscope, X-ray diffractometer, scanning electron microscopy, and transmission electron microscopy. The results showed that the addition of Fe effectively refined α-Zr slats, and the Zr3Fe compound phase was dispersed throughout the alloy. However, the composition line of the alloying elements in the phase diagram intersected with the Zr2Fe and β-Zr eutectic lines when the Fe content exceeded 6 at.%. Zr–Fe alloys were transformed from monocrystalline-eutectoid to eutectic-eutectoid reactions. The Zr3Fe compound phase accumulated inside the grain and at the grain boundary as a result of the eutectic reaction, which stabilized the microstructure of the Zr–Fe alloys. This seriously affected the mechanical and corrosion properties of the alloys. The mechanical and corrosion properties of the alloys were assessed by universal testing machine, dynamic microhardness tester, Vickers hardness tester, and electrochemical workstation. The mechanical and corrosion properties of Zr–2Fe were excellent due to the coupling effect of Zr3Fe and grain refinement. The surface of the Zr–Fe alloy was analyzed by X-ray photoelectron spectroscopy, revealing the presence of passivation film components ZrO2 and Fe2O3.

By selecting five key operational parameters—inlet temperature, operating temperature, anode humidity, cathode humidity, and operating pressure—and using PEMFC power density, membrane temperature difference, and membrane water content as performance indicators, simulations were conducted using 3D CFD modeling and orthogonal experiments to identify the most significant factors influencing PEMFC performance and determine the optimal operational parameter combination. The results show that working pressure has the most significant impact on PEMFC performance. Pressure variations cause significant changes in diffusion and heat conduction within the PEMFC. When the working pressure increases from 1.0 MPa to 3.0 MPa, the power density increases by approximately 11.2 %, but the temperature difference within the membrane increases by about 30.5 %. The difference between operating temperature and inlet temperature directly leads to changes in the temperature difference within the membrane. Moreover, changes in operating temperature greatly affect the water content within the proton exchange membrane, which in turn impacts the PEMFC's power density. When the operating temperature increases from 60 °C to 100 °C, the water content within the membrane decreases by approximately 50.5 %, and the power density decreases by 60.4 %. By optimizing the combination of operating parameters using a comprehensive scoring method, the temperature difference within the membrane can be controlled at 27.78 °C while ensuring the power density is increased to 0.92 W/cm2.

Aim: This in vitro study aimed to evaluate the effect of matrix metalloproteinase (MMP) inhibitors on the bond strength of resin-cemented fibre posts to radicular dentin under an aged-loaded condition. Materials and methods: Radicular dentin was prepared and irrigated by MMP inhibitor solution after root canal obturation in 60 extracted single-rooted teeth based on 6 groups: (1) 2% chlorhexidine (CHX) + loaded; (2) CHX + unloaded; (3) 0.5% benzalkonium chloride (BAC) + loaded; (4) BAC + unloaded; (5) 17% ethylenediaminetetraacetic acid (EDTA) + loaded; and (6) EDTA + unloaded. After final rinsing, all specimens were sliced cross-sectionally and kept in a water bath for 12 months of ageing. Groups 1, 3, and 5 were subjected to cyclic loading. Push-out tests were conducted using a universal testing machine, and failure mode was examined. The data were analysed using 3-way analysis of variance and post hoc tests at α = 0.05. Results: BAC + unloaded demonstrated the highest mean bond strength (3.12 ± 0.18 MPa; P < .001), while the BAC + loaded and CHX + loaded groups showed a significantly lower push-out bond strength than their unloaded counterparts. Mixed adhesive-cohesive failure was the most common failure mode observed. Conclusions: Without cycling loading, BAC was superior to CHX and EDTA in preserving the bond strength of resin-cemented fibre posts after 12 months of ageing. Loading significantly weakened the effectiveness of BAC and CHX in preserving the bond strength.

Titanium oxides (TiO2) nanostructures coating is helpful in improving the utilization of titanium in many areas due to its multifunctional properties. This study introduces a novel approach for the in-situ fabrication of nano cones-like structures of rutile titanium oxides (NCS–TiO2) on the surface of titanium utilizing femtosecond laser technology. Rutile titanium oxides were synthesized with a height of around 80 nm and a diameter of 100 nm, forming NCS that imparts higher hardness, wear resistance, and biocompatibility. Molecular dynamic simulation provides valuable insights into the three-stage formation process of NCS-TiO2. Molecular dynamic simulation revealed that the growth of rutile titanium oxides and the formation of nano cones-like structures are attributed to the interplay between femtosecond laser ablation and the accumulation of thermal energy. The proposed method offers a versatile and straightforward approach for creating functional surfaces on metal substrates, enabling broad applicability and ease of implementation, specifically in titanium and its alloys. This advancement holds great potential for expanding the scope of titanium-based materials and their applications, paving the way for improved mechanical properties and biocompatibility in diverse fields.

The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a serious global health threat. This raises an urgent need for the development of effective drugs against the deadly disease. SARS-CoV-2 non-structural protein 14 (NSP14) carrying RNA cap guanine N7-methyltransferase and 3′-5′ exoribonuclease activities could be a potential drug target for intervention. NSP14 of SARS-CoV-2 shares 98.7% of similarity with the one (PDB 5NFY) of acute respiratory syndrome (SARS) by ClustalW. Then, the SARS-CoV-2 NSP14 structures were modelled by Modeller 9.18 using SARS NSP14 (PDB 5NFY) as template for virtual screening. Based on the docking score from AutoDock Vina1.1.2, 18 small molecule drugs were selected for further evaluation. Based on the 5 ns MD simulation trajectory, binding free energy (ΔG) was calculated by MM/GBSA method. The calculated binding free energies of Saquinavir, Hypericin, Baicalein and Bromocriptine for the N-terminus of the homology model were −37.2711 ± 3.2160, −30.1746 ± 3.1914, −23.8953 ± 4.4800, and −34.1350 ± 4.3683 kcal/mol, respectively, while the calculated binding free energies were −60.2757 ± 4.7708, −30.9955 ± 2.9975, −46.3099 ± 3.5689, and −59.8104 ± 3.5389 kcal/mol, respectively, when binding to the C-terminus. Thus, the compounds including Saquinavir, Hypericin, Baicalein and Bromocriptine could bind to the N-terminus and C-terminus of the homology model of the SARS-CoV-2 NSP14, providing a candidate drug against SARS-CoV-2 for further study.

Background: Bioresorbable vascular grafts (BVGs) can transform biologically into active blood vessels and represent an alternative to traditional synthetic conduits, which are prone to complications such as infection and thrombosis. Although platelet-derived growth factors and c-Kit positive cells play an important role in smooth muscle cell (SMC) migration and proliferation in vascular injury, atherosclerosis, or allograft, their roles in the vascular remodeling process of an arterial BVG remains unknown. Thus, we assessed the neottisue formation on arterial BVG remodeling by administrating imatinib, which is both a platelet-derived growth factor receptor kinase inhibitor and c-Kit receptor kinase inhibitor, in a murine model. Methods: BVGs were composed of an inner poly(L-lactic-co-ε-caprolactone) copolymer sponge layer and an outer electrospun poly(L-lactic acid) nanofiber layer, which were implanted into the infrarenal abdominal aortas of C57BL/6 mice. After graft implantation, saline or 100 mg/kg of imatinib was administrated intraperitoneally daily for 2 weeks (n = 20 per group). Five mice in each group were scheduled to be humanely killed at 3 weeks and 15 at 8 weeks, and BVGs were explanted for histologic assessments. Results: Graft patency during the 8-week observational period was not significantly different between groups (control, 86.7% vs imatinib, 80.0%; P > .999). Neotissue formation consisting of endothelialization, smooth muscle proliferation, and deposition of collagen and elastin was not observed in either group at 3 weeks. Similar endothelialization was achieved in both groups at 8 weeks, but thickness and percent area of neotissue formation were significantly higher in the control group than in the imatinib group, (thickness, 30.1 ± 7.2 μm vs 19.6 ± 4.5 μm [P = .001]; percent area, 9.8 ± 2.7% vs 6.8 ± 1.8% [P = .005]). Furthermore, SMC layer and deposition of collagen and elastin were better organized at 8 weeks in the control group compared with the imatinib group. The thickness of SMC layer and collagen fiber area were significantly greater at 8 weeks in the control group than in the imatinib group (P < .001 and P = .026, respectively). Because there was no difference in the inner diameter of explanted BVGs (831.7 ± 63.4 μm vs 841.8 ± 41.9 μm; P = .689), neotissue formation was thought to advance toward the outer portion of the BVG with degradation of the polymer scaffold. Conclusions: Imatinib attenuates neotissue formation during vascular remodeling in arterial bioresorbable vascular grafts (BVGs) by inhibiting SMC layer formation and extracellular matrix deposition. : Clinical Relevance: This study demonstrated that imatinib attenuated neotissue formation during vascular remodeling in arterial Bioresorbable vascular graft (BVG) by inhibiting smooth muscle cell formation and extracellular matrix deposition. In addition, as imatinib did not modify the inner diameter of BVG, neotissue advanced circumferentially toward the outer portion of the neovessel. Currently, BVGs have not yet been clinically applied to the arterial circulation. The results of this study are helpful for the design of BVG that can achieve an optimal balance between polymer degradation and neotissue formation.

Honokiol (HK) usage is greatly restricted by its poor aqueous solubility and limited oral bioavailability. We synthesized and characterized a novel phosphate prodrug of honokiol (HKP) for in vitro and in vivo use. HKP greatly enhanced the aqueous solubility of HK (127.54 ± 15.53 mg/ml) and the stability in buffer solution was sufficient for intravenous administration. The enzymatic hydrolysis of HKP to HK was extremely rapid in vitro (T1/2 = 8.9 ± 2.11 s). Pharmacokinetics studies demonstrated that after intravenous administration of HKP (32 mg/kg), HKP was converted rapidly to HK with a time to reach the maximum plasma concentration of ∼5 min. The prodrug HKP achieved an improved T1/2 (7.97 ± 1.30 h) and terminal volume of distribution (26.02 ± 6.04 ml/kg) compared with direct injection of the equimolar parent drug (0.66 ± 0.01 h) and (2.90 ± 0.342 ml/kg), respectively. Furthermore, oral administration of HKP showed rapid and improved absorption compared with the parent drug. HKP was confirmed to maintain the bioactivity of the parent drug for ameliorating ischemia-reperfusion injury by decreasing brain infarction and improving neurologic function. Taken together, HKP is a potentially useful aqueous-soluble prodrug with improved pharmacokinetic properties which may merit further development as a potential drug candidate. Keywords: Phosphate prodrug, Honokiol, Pharmacokinetics, Focal cerebral ischemia-reperfusion

The aim of commercial pig breeding programs is to maximize the number of pigs produced per sow per year. Given that sows exhibit an estrus during lactation is a potential means of increasing productivity of a pig breeding herd without reducing in lactation length, conventionally, weaning of piglets at a relatively young age is often related to post-weaning piglet performance which compromises piglet welfare. Therefore, intermittent suckling (IS) is a management technique in which lactating sows are separated from their piglets for a fixed period of the days and allowing sows to continue nursing piglets while exhibiting estrus and being breed during lactation, thereby promoting both piglet well-being and sow reproductive performance [1]. For this study, primiparous sows (PP) were exposed to 28 day (D28) lactation with intermittent suckling (IS) during the final week prior to weaning. The sows detected to be in estrus during lactation were either bred at this first estrus (FE) during lactation (IS21FE), or were “skipped” and bred at their second estrus which occurred after final weaning at D28 (IS21SE). Despite the benefits of IS, the effects of the maternal physiology related to breeding during lactation on embryonic transcriptome are largely unknown. Recent advances in the ability to assess embryonic gene expression in both sexes have made these analyses possible. Here, we describe the experimental procedures of two color microarray analyses and annotation of differentially expressed (DE) genes in detail corresponding to data deposited at NCBI in the Gene Expression Omnibus under accession number GSE53576 and GSE73020 for day 9 embryos (D9E) and day 30 embryos (D30E) respectively. Although only a few DE genes were discovered between IS21FE and IS21SE in both sexes from D9E or D30E, the raw data are still valuable for future use to understand the gene expression profiling from two different developmental stages.

Maintenance of normal endothelial function is critical to various aspects of blood vessel function, but its regulation is poorly understood. In this study, we show that disruption of baseline fibroblast growth factor (FGF) signaling to the endothelium leads to a dramatic reduction in let-7 miRNA levels that, in turn, increases expression of transforming growth factor (TGF)-β ligands and receptors and activation of TGF-β signaling, leading to endothelial-to-mesenchymal transition (Endo-MT). We also find that Endo-MT is an important driver of neointima formation in a murine transplant arteriopathy model and in rejection of human transplant lesions. The decline in endothelial FGF signaling input is due to the appearance of an FGF resistance state that is characterized by inflammation-dependent reduction in expression and activation of key components of the FGF signaling cascade. These results establish FGF signaling as a critical factor in maintenance of endothelial homeostasis and point to an unexpected role of Endo-MT in vascular pathology.

Atopic dermatitis (AD) is a chronic inflammatory skin disease where Th2-type immune responses are dominant. In the lesional skin of AD, keratinocytes show differentiation defects and secrete proinflammatory cytokines and chemokines, amplifying Th2-type responses in AD. We previously reported that inducible loss of B-cell lymphoma 6 (Bcl6), a transcription repressor and a master transcriptional regulator of follicular helper T cells and germinal center B cells, in the whole body results in upregulation of Th2-related cytokines in mouse skin. However, the role of Bcl6 in keratinocytes remains to be clarified. Here, we observed that BCL6 positively regulates the expression of keratinocyte differentiation markers and plasma membrane localization of adherence junctional proteins in keratinocyte cell culture. Although keratinocyte-specific loss of Bcl6 alone did not induce AD-like skin inflammation, it aggravates MC903-induced AD-like skin inflammation in mice. In addition, Bcl6 expression is decreased in the epidermis of lesional skin from MC903-induced AD-like skin inflammation in mice. These results strongly suggest that Bcl6 downregulation in keratinocytes contributes to the development and aggravation of AD-like skin inflammation in mice., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The presence of a significant number of melanocytes in the ovary and follicular membrane of Silky Fowl suggests their potential involvement in follicle development. Currently, there is a lack of available data regarding to the isolation of primary melanocytes from adult chickens. To date, primary melanocytes and their in vitro culture system have been successfully conducted in the peritoneum of chicken embryos. Herein, melanocytes from silky fowl ovaries were isolated and identified. Silky Fowl ovaries were obtained by mixed digestion of 0.1% collagenase II and 0.25% trypsin-EDTA. Melanocytes could be further purified and cultured up to 5 generations in vitro. RNA-seq analysis was used to investigate whether there were differences in the functional status of melanocytes in different tissues and developmental stages. Consequently, differential gene expressions between peritoneal and ovarian melanocytes were compared. These findings demonstrated that the Silky Fowl ovary had higher expression levels of genes involved in the production of sexual hormones and melanogenesis, while those of melanocytes derived from the peritoneum were involved in amino acid metabolism, lipid synthesis, and overall metabolic rates. This suggests that the role of melanocytes is dependent on the origin tissue and developmental stage, and is tightly connected to the function of the specific source tissue from which the cells were derived. This study provides a method for isolating adult melanocytes and serve as a basis for further investigate the effect of SFOM on germ cells., (Copyright © 2024. Published by Elsevier Inc.)

Introduction: In CameL phase 3 study (ClinicalTrials.gov: NCT03134872), addition of camrelizumab to first-line chemotherapy significantly improved the progression-free survival in patients with stages IIIB to IV nonsquamous NSCLC. Here, we present outcomes after a minimum follow-up of 43.9 months since last patient randomization., Methods: Eligible patients were randomized 1:1 to 4 to 6 cycles of camrelizumab plus carboplatin and pemetrexed or chemotherapy alone every 3 weeks, followed by maintenance camrelizumab plus pemetrexed or pemetrexed only (n = 205 and 207, respectively). Total camrelizumab exposure was up to 2 years., Results: As of January 31, 2022, camrelizumab plus chemotherapy exhibited substantially improved overall survival over chemotherapy alone (median, 27.1 versus 19.8 mo; hazard ratio = 0.72 [95% confidence interval: 0.57-0.92]). In the chemotherapy-alone group, 95 patients (45.9%) crossed over to camrelizumab monotherapy. After adjustment for crossover, the survival benefit with camrelizumab plus chemotherapy was more pronounced (adjusted hazard ratio = 0.55 [95% confidence interval: 0.42-0.71]). In camrelizumab plus chemotherapy group, 33 patients completed 2 years of camrelizumab. Objective response rate was 97.0%, with ongoing responses in 17 of the 32 responses (53.1%), and 93.9% (31 of 33) of the patients were alive at data cutoff. Safety profiles were consistent with the previous report, and no obvious evidence of cumulative toxicity was found with long exposure to camrelizumab., Conclusions: Camrelizumab plus carboplatin and pemetrexed provides long-term survival benefit over chemotherapy, with manageable toxicity and remarkable and durable response in patients receiving 2 years of camrelizumab, further supporting camrelizumab combination as first-line treatment for advanced nonsquamous NSCLC., (Copyright © 2023 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Alteration of platelet status associates with decompensation and death in cirrhosis, while its effect on portal vein thrombosis (PVT) remains unclear. We aimed to retrospectively investigate whether PVT associates with platelet-fibrin clot strength and platelet activation in decompensated cirrhosis., Methods: Platelet-fibrin clot strength (G) was measured by thromboelastography (TEG). Platelet activation was reflected by plasma concentrations of soluble p-selectin (sPs) and a platelet aggregation test adjusted for platelet counts., Results: Among 166 patients, 45 had PVT. The platelet count was significantly lower in PVT. While the G value was positively correlated with platelet count (ρ = 0.74, P < 0.01), increased G was associated with PVT after adjusting for platelet count in the logistic regression (P = 0.04). The normalized G value according to the linear relation with platelet count was calculated as follows: G platelet  = [(G - 2622)/platelet count]. This coefficient had no correlation with platelet count and was an independent risk factor of PVT (OR = 1.03, CI 95% : 1.01-1.05, P = 0.012). In two subanalyses, the collagen-induced platelet aggregation (n = 37, P = 0.029) and plasma concentration of sPs (n = 56, P = 0.001) adjusted for platelet count were significantly higher in PVT., Conclusion: This study showed a positive correlation of high platelet-fibrin clot strength detected via TEG and platelet activation with PVT in decompensated cirrhosis., Competing Interests: Conflict of Interest The authors have no conflicts of interest to disclose., (Copyright © 2022. Published by Elsevier Ltd.)

Nighttime use of artificial light is usual and essential in these modern times. Although light exposure at night (LAN) is reportedly a risk factor of several diseases, epidemiological studies on indoor LAN levels are still limited. Hence, the present study aimed to measure bedroom LAN levels by using light meters in a larger sample than in previous studies, and to evaluate the associations with comprehensive health outcomes. Out of 3012 participants, 2947 (mean age, 69.3 years; female, 60.6%) completed the bedroom LAN intensity measurement. The median bedroom LAN intensity was 1.0 lux (interquartile range, 0.2-4.0 lux). In a multivariable analysis adjusted for potential confounding factors, the highest quartile group of bedroom LAN intensity had significantly higher body weight, body mass index, abdominal circumference, and low-density lipoprotein cholesterol than the lowest quartile group. The group with a median LAN intensity ≥10 lux had significantly higher white blood cell counts and had significantly lower high-density lipoprotein cholesterol levels than the group with a median LAN intensity <10 lux. In addition, the groups with median LAN intensities ≥3 and ≥10 lux had significantly higher odds ratios for sleep disturbances and depressive symptoms than the group with <3 and <10 lux, respectively. Therefore, the present study provided real-world data on bedroom LAN levels as a marker for indoor light pollution in a large sample and suggested that higher bedroom LAN levels are significantly associated with parameters of obesity, dyslipidemia, systemic inflammation, sleep disturbances, and depressive symptoms., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Drs. Obayashi and Saeki report financial support was provided by YKK AP Inc., Ushio Inc., Tokyo Electric Power Company, EnviroLife Research Institute Co., Ltd., Sekisui Chemical Co., Ltd, LIXIL Corp., KYOCERA Corp., ENDO Lighting Corp., and KANEKA Corp., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

People with Parkinson's disease (PD) develop postural imbalance and falls. Galvanic Vestibular Stimulation (GVS) may potentially improve postural balance in humans and hence reduce falls in PD. This systematic review and meta-analysis investigate the effects of GVS on postural balance in PD. Six separate databases and research registers were searched for cross-over design trials that evaluated the effects of GVS on postural balance in PD. We used standardized mean difference (Hedges' g) as a measure of effect size in all studies. We screened 223 studies, evaluated 14, of which five qualified for the meta-analysis. Among n = 40 patients in five studies (range n = 5 to 13), using a fixed effects model we found an effect size estimate of g = 0.43 (p < 0.001, 95% CI [0.29,0.57]). However, the test for residual heterogeneity was significant (p < 0.001), thus we used a random effects model and found a pooled effect size estimate of 0.62 (p > 0.05, 95% CI [- 0.17, 1.41], I2 = 96.21%). Egger's test was not significant and thus trim and funnel plot indicated no bias. To reduce heterogeneity, we performed sensitivity analysis and by removing one outlier study (n = 7 patients), we found an effect size estimate of 0.16 (p < 0.05, 95% CI [0.01, 0.31], I2 = 0%). Our meta-analysis found GVS has a favourable effect on postural balance in PD patients, but due to limited literature and inconsistent methodologies, this favourable effect must be interpreted with caution., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Phosphorus (P) recovery from waste streams is an essential choice due to the coming global P crisis. One promising solution is to recover P by microbial electrolysis cell (MEC). Both the P recovery effectiveness and product quality are of critical importance for application. In this study, a two-chamber MEC was constructed and the effects of applied voltage, NaAc concentration, Mg/P molar ratio, N/P molar ratio, and initial P concentration on P recovery and product purity were explored. The maximum P recovery efficiency of 99.64 % and crystal accumulation rate over 106.49 g/m 3 -d were achieved. Struvite (MAP) was confirmed as the final recovered product and the purity obtained could reach up to 99.95 %. Besides, higher applied voltage, N/P molar ratio and initial P concentration could promote P recovery efficiency, while the purity of MAP showed correlation with applied voltage, Mg/P molar ratio, N/P molar ratio and initial P concentration. The correlation between NaAc concentration and both of the above was not very significant. A lower energy consumption of 4.1 kWh/kg P was observed at the maximum P recovery efficiency. In addition, the efficiency of P recovery from real wastewater also could reach nearly 88.25 %. These results highlight the promising potential of efficient phosphorus recovery from P-rich wastewater by MEC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

As an essential component in constructed wetland-microbial fuel cells (CW-MFC) system, the macrophytes play multiple roles in bioelectricity generation and decontaminants performance. However, the interrelation between macrophytes roots and cathode has not been fully investigated despite the fact that plant cultivation strategy is a critical issue in practice. For the first time, this study was designed to explore the interaction between macrophytes and cathode in CW-MFC by planting Cyperus altrnlifolius at relatively different positions from the cathode. The results showed that plants exhibited higher bioelectricity generation and dramatically improved pollution removal, as well as the improved richness and diversity of cathode microbes. More significantly, the relative locations between the plant roots and the cathode could lead to different cathode working patterns, while the optimal cathode pattern "plant root-assisted bio- & air-cathode" was formed when the plant roots are directly placed on the air-cathode layer in CW-MFC. The insight into the plant root and cathode relationship lies in whether the "multi-function cathode" can be established. This study contributes to increase the knowledge regarding the presence and behavior of plant roots and cathode throughout a CW-MFC system., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Rivers in urbanised cities are often polluted, black, and odorous, with poor water quality and deteriorated ecology. Despite many river restoration studies, assessments of ecological responses to river restoration practices remain scant. Benthic animals are useful biological indicators showing the change and succession of river ecosystems; however, previous studies have mainly focussed on a few target species without considering overall ecosystem integrity. Here, we used a multi-index biological assessment method, benthic index of biological integrity (B-IBI) to assess ecological responses to river restoration of the Shahe River in subtropical region of China. Spatiotemporal changes in the macrobenthos community structure after restoration were monitored to explore species succession. We found that the number of macrobenthos species increased from 16 to 42, with the emergence of some pollution-sensitive species during the restoration period. Molluscs showed widespread recovery, and their relative proportions almost doubled from 12.5% to 24.4%. Oligochaetes and chironomids were the pioneer species in the recovering communities, while gastropod molluscs and pollution-sensitive aquatic insects were transitional species that first settled during the initial recovery period. Based on our survey data, 25 candidate metrics were selected, and five core metrics (total taxa, Simpson diversity index, percentage of crustaceans and molluscs, percentage of predators, and percentage of collector-gatherers) were identified after screening to establish the B-IBI. Our analysis revealed a distinct improvement in the overall health of the river, with the proportions of "excellent" and "good" sites increasing from zero to 28.6% and from 14.3% to 42.9%, respectively. A correlation analysis indicated that water flow, molluscs, and total phosphorus content were the three drivers of ecological recovery in the Shahe River. Overall, our study demonstrates the importance of governance and restoration of rivers in tropical and subtropical cities, and provides valuable evidence that can guide the design and evaluation of river restoration works., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

Background: First-trimester cervical length for the prediction of spontaneous preterm delivery remains controversial. A better method for the measurement of the first-trimester cervical length and additional cervical ultrasound parameters for the identification of women at high risk for spontaneous preterm delivery are needed., Objective: This study aimed to compare the predictive value of cervical length measured by 2 different methods in the first trimester of pregnancy to predict spontaneous preterm delivery and to explore the potential value of first-trimester cervical shear-wave elastography for the prediction of spontaneous preterm delivery., Study Design: This was a prospective study in unselected singleton pregnancies at 11 +0 to 13 +6 weeks' gestation. Cervical length was measured by the following 2 methods in the base-cohort population: (1) a linear distance between the 2 ends of the glandular area around the endocervical canal (single-line method: cervical length-s) and (2) a sum of the linear distance from the internal os to the greatest cervical curvature and the linear distance from this point to the external os (2-line method: cervical length-t). In a substudy, cervical shear-wave elastography scores for 9 regions of interest (inner, middle, and external parts of anterior lip, endocervical canal, and posterior lip) in midsagittal plane were also obtained by transvaginal ultrasonography. The screening performance of the first-trimester cervical length measured by the 2 different methods for the prediction of spontaneous preterm delivery was assessed by receiver operating characteristics curve analysis. The areas under the curves were compared using a DeLong test. The predictive performance of a soft cervix (mean elastography scores with multiple of median <5th, 10th, 15th, 20th, and 25th percentile) for spontaneous preterm delivery was also determined., Results: Among a total of 2316 included pregnancies, spontaneous delivery at <37 and <34 weeks' gestation occurred in 111 cases (4.8%) and 20 cases (0.9%), respectively. In the total study population, when compared with the term delivery group, the median cervical length-t was shorter in women with spontaneous delivery at <34 weeks' gestation (36.9 mm vs 35.1 mm; P=.015), but there was no clear correlation for cervical length-s. Receiver operating characteristics curves demonstrated that cervical length-t achieved better performance in predicting spontaneous delivery at <34 weeks' gestation (area under the curve, 0.658 vs 0.573; P<.01) than cervical length-s. The best combined model to predict spontaneous delivery at <34 weeks' gestation was provided by cervical length-t and history of preterm delivery (area under the curve, 0.692). In the substudy, a soft cervix with a mean elastography scores multiple of median <10th percentile had a relative risk of 7.8 (95% confidence interval, 2.1-28.6) for spontaneous delivery at <34 weeks' gestation; the detection rate was 44.4% at a false-positive rate of 9.0%., Conclusion: The 2-line approach provides a better estimate of the actual first-trimester cervical length and achieves better performance as a screening tool for spontaneous preterm delivery at <34 weeks' gestation than the conventional measurement. A soft cervix as determined by shear-wave elastograpthy in the first trimester is associated with an increased risk for subsequent spontaneous preterm delivery., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The combination sequence of traditional hybrid constructed wetlands (HCWs) affects the removal of nitrogen in raw sewage, but the effect of the combination sequence on nitrogen removal pathway have seldom been reported, especially the specific conditions allowing anammox to occur. Three-stage HCWs, namely vertical flow (VF), horizontal flow (HF) and surface flow (SF) constructed wetlands, were arranged in six different sequences to investigate nitrogen removal efficiencies and microbial removal pathways using metagenomic and stable isotope analyses. Results showed that the combination sequence significantly affected nitrogen removal pathways in HCWs. We found the best removal of total nitrogen (~50%) and ammonium (NH 4 + -N, ~99%) in HCWs with a VFCW in the 1st stage. Metagenomic results and stable isotope analyses further indicated that simultaneous nitrification and heterotrophic denitrification were the main pathways in unsaturated VFCW, which depended on the energy substance and electron donor supplied by chemical oxygen demand (COD Cr ) in raw sewage. Nitrifier, anammox bacteria and autotrophic denitrifies prevailed in the subsequent saturated CWs, which tend to nitrogen loss by partial nitrification and anammox in HFCW when fed with NH 4 + -N wastewater with low COD Cr . Providing NH 4 + -N and oxygen in low COD Cr wastewater was the essential step to facilitate anammox process in HFCW. It implied that the problem of poor nitrogen removal due to carbon limitation could be overcome by optimizing conditions in anammox's favor., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

Antibiotic resistance genes (ARGs) commonly detected in wastewater can potentially lead to a health crisis. Constructed wetlands (CWs) remove ARGs and sulfonamides (SAs) from wastewater, but the importance of plants in the process is seldom reported. We compared the effect of three wetland plant species (Cyperus alternifolius, Juncus effuses, and Cyperus papyrus), sample distance from the root, and SA presence on the environmental abundance of class 1 integron (intI1) and SA resistance genes (sul) using specially designed CW rhizoboxes. Quantitative polymerase chain reaction revealed that the relative abundance of the target genes in planted CWs, especially in C. alternifolius planted CWs, was significantly lower than that in unplanted CWs (P < 0.05). The substrate in the rhizosphere or near-/moderate-rhizosphere (closest to the root) showed the lowest average relative abundance of the target genes, while the bulk substrate (without the root) showed the highest abundance of these genes, irrespective of the planted species. Further, the influence of plants was more evident after 8 weeks of wastewater treatment. The trend was the same in SA-treated and untreated groups, although the relative abundance of the target genes was significantly higher in the former (P < 0.05). The weaker correlation between the intI1 and sul genes in the rhizosphere and near-/moderate-rhizosphere in comparison to the bulk substrate in the SA group suggested that the risk of horizontal gene transfer was probably higher in the bulk substrate and unplanted CW. A partial least-squares path model revealed that dissolved organic carbon and oxygen content significantly influenced SA concentration, microbial community, and intI1 genes, and then shaping the sul genes together. Finally, redundancy analysis suggested that abundance of sul genes was influenced by bacteria enriched in the bulk substrate and unplanted CWs. The findings provide new insights into the importance for controlling risk of ARGs by wetland plants., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

The risk of cardiovascular disease (CVD) in patients with rheumatoid arthritis (RA) is higher than that in patients without RA, and it is even higher than that in patients with diabetes. Autoimmune-mediated inflammation is observed in patients with RA, resulting in endothelial dysfunction, oxidative stress and activation, and vascular migration of white blood cells. Traditionally, RA-associated CVD was assumed to be mediated by disease-related inflammation, resulting in atherosclerosis (AS). However, this concept has been challenged because treatment with anti-rheumatic drugs, such as methotrexate or proinflammatory cytokine antagonists, such as tumor necrosis factor-alpha (TNF-α) inhibitors, did not reduce the risk of CVD in patients with RA. Current cardiovascular guidelines recommend screening and treatment of CVD risk factors in patients with RA but without clear biomarkers and treatment goals. There is no scientific basis for establishing therapeutic targets for cardiovascular risk factors in RA. Numerous studies have shown that the mechanism of early cardiac dysfunction in patients with RA may occur prior to AS. Therefore, it is crucial to explore the related mechanisms to prevent early cardiac dysfunction in patients with RA., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Neural precursor cells (NPCs) transplanted into the adult neocortex generate neurons that synaptically integrate with host neurons, supporting the possibility of achieving functional tissue repair. However, poor survival and functional neuronal recovery of transplanted NPCs greatly limits engraftment. Here, we test the hypothesis that combining blood vessel-forming vascular cells with neuronal precursors improves engraftment. By transplanting mixed embryonic neocortical cells into adult mice with neocortical strokes, we show that transplant-derived neurons synapse with appropriate targets while donor vascular cells form vessels that fuse with the host vasculature to perfuse blood within the graft. Although all grafts became vascularized, larger grafts had greater contributions of donor-derived vessels that increased as a function of their distance from the host-graft border. Moreover, excluding vascular cells from the donor cell population strictly limited graft size. Thus, inclusion of vessel-forming vascular cells with NPCs is required for more efficient engraftment and ultimately for tissue repair., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Constructed wetland-microbial fuel cell (CW-MFC) has exhibited the performance discrepancy between using granular activated carbon (GAC) and columnar activated carbon (CAC) as air-cathode materials. No doubt, this is linked with electrochemical performance and decontaminants characteristics in the CW-MFC system. To provide insight into this performance discrepancy, three CW-MFCs were designed with different carbon-material to construct varied shapes of air-cathodes. The results showed that the ring-shaped cathode filled with GAC yielded a highest voltage of 458 mV with maximum power density of 13.71 mW m -2 and >90% COD removal in the CW-MFC system. The electrochemical characteristics and the electron transport system activity (ETSA) are the driven force to bring the GAC a better electron transportation and oxygen reduction reaction (ORR). This will help elucidating underlying mechanisms of different activated carbon for air-cathode and thus promote its large application., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: Passive body heating can have an antidepressant effect by activating warm-sensitive neural pathways associated with affective functions. Interventional studies showed that patients with depression had reduced depressive symptoms after passive body heating. However, the effect of hot water bathing at home on depressive symptoms in the general population remains unclear. Thus, we evaluated the association between objectively measured hot water bathing and depressive symptoms among older adults., Design: Cross-sectional analysis., Setting: A baseline survey of community-based cohort study in Japan., Participants: Community-dwelling older volunteers (n = 1,103; mean age: 72.0 years)., Measurements: The authors evaluated bathing conditions and distal skin temperature for 2 consecutive days. Depressive symptoms were defined as the 15-item Geriatric Depression Scale score of ≥6., Results: Logistic regression showed that the no bathing group (adjusted odds ratio [OR] 2.60, 95% confidence interval [CI] 1.36-4.95, χ² = 8.40, degrees of freedom [df] = 1) and the either-day bathing group (adjusted OR 1.68, 95% CI 1.11-2.56, χ² = 5.89, df = 1) had higher odds of depressive symptoms than the both-day bathing group independent of potential confounders including age, sex, body mass index, alcohol intake, income, living alone, hypnotic use, diabetes, and physical activity. Shorter interval from bathing to bedtime was significantly associated with lower odds of depressive symptoms and higher nighttime distal skin temperature after adjusting for water temperature and duration., Conclusion: A higher frequency of hot water bathing and shorter interval from bathing to bedtime were associated with lower odds of depressive symptoms., (Copyright © 2021 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

Frost-free areas have suitable climate for wetland plant growth and constructed wetlands (CW) technology. Information on the quantification of plant biomass and uptake efficiency in field-scale CWs is limited in these climates. The removal efficiency of total nitrogen (TN), total phosphorus (TP), chemical oxygen demand (COD), and total suspended solids (TSS) in wastewater from sewage plants, domestic sewage, and an industrial park in 15 rural and urban CWs in Guangdong Province, China, with an average temperature of 30 °C was evaluated. The effects of influent concentration, hydraulic load, the wastewater's physicochemical properties, operating conditions, and plant uptake were analysed. The mean removal rates were 40.0%, 45.2%, 41.1%, and 71.7% for TN, TP, COD, and TSS, respectively, which were higher than the removal load of the field-scale CWs in temperate regions. Removal loads of TN, TP, COD, and TSS were highest in CWs that have been operating for 5-6 years, treating wastewater volumes of over 1 m 3 /m 2 ·d. The removal efficiency was mainly related to the inflow concentration and less affected by the type of CWs. Nutrient accumulation trends were primarily linked to influent concentrations (TN: r 2 = 0.89, P = 0.007; TP: r 2 = 0.96, P = 0.001) and plant biomass (TN: r 2 = 0.96, P = 0.001; TP: r 2 = 0.92, P = 0.004). Plant biomass contributed 2%-29% and 2%-70%, respectively, to removing N and P in CWs. The average uptake concentration of N and P in aboveground plant organs (15.66 ± 4.44 mg N/g, 2.15 ± 1.18 mg P/g) was generally higher than that of other temperate plants. A strong relationship between TN and TP in the biomass was also observed; however, the relationship is only restricted by the influent TP concentration. Arundo donax is well-adapted for nutrient accumulation and adaptation and is an ideal wetland plant to purify wastewater in frost-free climates., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021. Published by Elsevier B.V.)

In black-boned chicken, melanocytes are widely distributed in their inner organs. However, the roles of these cells are not fully elucidated. In this study, we used 3-wk-old female Silky Fowl to investigate the functions of melanocytes under infection with infectious bursal disease virus (IBDV). We found the melanocytes in the bursa of Fabricius involved in IBDV infection shown as abundant melanin were transported into the nodule and lamina propria where obvious apoptotic cells and higher expression of BAX were detected. Genes related to the toll-like receptor (TLR) signaling pathway were highly detected by quantitative PCR, including TLR1, TLR3, TLR4, TLR15, myeloid differential protein-88, interferon-α, and interferon-β. We then isolated and infected primary melanocytes with IBDV in vitro and found that higher expressions of immune genes were detected at 24 and 48 h after infection; the upregulated innate and adaptive immune genes were involved in the pathogenesis of IBDV infection, including TLR3, TLR7, interleukin 15 (IL15), IL18, IL1rap, CD7, BG2, ERAP1, and SLA2. These changes in gene expression were highly associated with microtubule-based movement, antigen processing and presentation, defense against viruses, and innate immune responses. Our results indicated that the widely distributed melanocytes in Silky Fowl could migrate to play important innate immune roles during virus infection., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Rheumatoid arthritis (RA) is an autoimmune disease targeting the synovium. Previous studies have found that IgD may be a potential target for the treatment of RA. We designed a new type of fusion protein, hIgDFc-Ig (DG), to block the binding of IgD to IgD receptor (IgDR). In this study, we found that DG has a significant therapeutic effect in mice with collagen-induced arthritis (CIA). DG improved the claw of irritation symptoms in these mice, inhibited the pathological changes in spleen and joint tissues, and had a moderating effect on B cell subsets at different inflammatory stages. Moreover, DG could also decrease the levels of IgA, IgD, IgM and IgG subtypes of immunoglobulin in the serum of mice with CIA. In vitro, B cell antigen receptor (BCR) knockout Ramos cells were established using the CRISPR/Cas9 technology to further study the activation of BCR signalling by IgD and the effect of DG. We found that the therapeutic effect of DG in mice with CIA may be achieved by inhibiting the activation of BCR signalling by IgD, which may be related to the activation of Igβ. In summary, DG may be a potential biological agent for the treatment of RA and it has broad application prospects in the future., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Aims: PTEN induced putative kinase 1 (PINK1)-mediated mitophagy process is tightly associated with various age-dependent diseases in mammals. The roles of miRNAs (miRNAs) in the PINK1-mediated mitophagy process are not fully understood. Here we discovered that miR-34a-5p suppresses PINK1 expression directly though two post-transcriptional non-classical binding modes, resulting in inhibition of PINK1-mediated mitophagy process., Main Methods: For in vivo experiments, brains were dissected from 8 weeks old and 40 weeks old C57BL/6 male mice to measure miR-34a-5p expression and PINK1 expression. For in vitro experiments, overexpression of miR-34a-5p mimics in HEK293 cells was performed to investigate the effect of miR-34a-5p on PINK1 expression and its regulatory mechanism, parkin recruitment and mitophagy process., Key Findings: The level of miR-34a-5p was upregulated and the level of PINK1 mRNA was downregulated in brains of aged mice. Both the 3'-untranslated region (3'UTR) and the Coding DNA sequence (CDS) of PINK1 mRNA were bound to the non-seed region of miR-34a-5p, rather than the seed region, resulting in a decrease in PINK1 expression. Endogenous miR-34a-5p knockout increased PINK1 expression. Further results indicated that miR-34a-5p inhibits mitophagy process by reduction of PINK1. miR-34a-5p hinders phosphorylated Ser65-ubiquitin (pS65-Ub) accumulation, prevents the mitochondrial recruitment of Parkin, attenuates ubiquitination and delays the clearance of damaged mitochondria., Significance: We firstly found that miR-34a-5p suppresses PINK1 directly and further regulates mitophagy through non-canonical modes. This finding hints at a crucial role of miR-34a-5p implicated in accelerating the pathogenesis of age-related neurological diseases., (Copyright © 2021 Elsevier Inc. All rights reserved.)

By 17 October 2020, the severe acute respiratory syndrome coronavirus (SARS-CoV-2) has caused confirmed infection of more than 39,000,000 people in 217 countries and territories globally and still continues to grow. As environmental professionals, understanding how SARS-CoV-2 can be transmitted via water and air environment is a concern. We have to be ready for focusing our attention to the prompt diagnosis and potential infection control procedures of the virus in integrated water and air system. This paper reviews the state-of-the-art information from available sources of published papers, newsletters and large number of scientific websites aimed to provide a comprehensive profile on the transmission characteristics of the coronaviruses in water, sludge, and air environment, especially the water and wastewater treatment systems. The review also focused on proposing the possible curb strategies to monitor and eventually cut off the coronaviruses under the authors' knowledge and understanding., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 Elsevier B.V. All rights reserved.)

Background & Aims: Splenomegaly is usually taken as a consequence of liver cirrhosis. However, as a risk factor for cirrhosis, the impacts of spleen-liver axis on the development of cirrhosis are largely unknown. This study focused on the impacts of splenomegaly on the development of cirrhosis and assessment of the effects of celecoxib, a selective COX-2 inhibitor, on the splenomegaly and cirrhotic liver., Materials and Methods: Liver cirrhosis was induced by thioacetamide (TAA). Sixty rats were randomly divided into control, TAA-16w, TAA + celecoxib groups and normal, TAA + sham, TAA + splenectomy groups. Hepatic stellate cells (HSCs) or hepatocytes were co-cultured with splenocytes from those groups., Results: Splenocytes of cirrhotic rats stimulated the HSCs activation and induced hepatocyte apoptosis via enhancing oxidative stress. The hepatic levels of NOX-4 and the in situ O 2 - were profoundly reduced in TAA + splenectomy group by 50.6% and 18.5% respectively, p < 0.05. Celecoxib significantly decreased the hepatic fibrotic septa induced with TAA by 50.8%, p < 0.05. Splenic lymphoid tissue proliferation and proinflammatory cytokines of the cirrhotic rats were also obviously suppressed by celecoxib, p < 0.05. Compared with the HSC or hepatocyte cell line co-cultured with the cirrhotic splenocytes, the expression of alpha-SMA, NOX-4, in situ O 2 - or the levels of cleaved caspase3 and NOX-4 were significantly decreased in those cell lines co-cultured with cirrhotic splenocytes treated by celecoxib, p < 0.05., Conclusion: Splenomegaly contributed to the development of liver cirrhosis through enhancing oxidative stress in liver. Celecoxib could effectively ameliorate liver cirrhosis via reducing inflammatory cytokines and immune cells derived from spleen and suppressing oxidative stress., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Foxp3 + regulatory T cells (Tregs) are essential for the prevention of autoantibody and allergen-specific IgE production. Treg deficiency causes an elevation of the serum levels of these pathogenic antibodies, accompanied by spontaneous germinal center (GC) formation. However, it remains to be determined whether excessive and pathogenic antibody production induced by Treg deficiency requires a GC response. Here, we demonstrate that spontaneous antibody production observed in Foxp3 conditional-knockout mice did not need GC formation. Foxp3 and Bcl6 conditional-double knockout mice exhibited spontaneous elevations of IgG1, IgG2c, and IgE levels even though they showed impaired production of IgG1 and IgE specific for the immunized antigen. Furthermore, the IgG1 and IgE antibodies specific for auto- and food-antigens were produced independently of GCs. These data suggested that a GC response was unnecessary for pathogenic antibody production caused by Treg deficiency., Competing Interests: Declaration of competing interest The authors declare no conflict of interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Foxp3 + regulatory T cells (Tregs) are crucial for maintaining tolerance to self-antigens and preventing autoimmune diseases. Loss of Foxp3 expression leads to autoimmunity and disrupts humoral immune responses, including hyperproduction of immunoglobulin E (IgE). Elucidation of how Tregs control antibody production can lead to the development of new therapies for autoimmune and allergic diseases. However, premature death of Foxp3-deficient mice makes it difficult to analyze the roles of Tregs in humoral immunity of adult mice. In this study, we developed Foxp3 conditional-knockout mice (Foxp3 flox R26 CreERT2 ) in which the Foxp3 gene was inducibly deleted by tamoxifen administration. After oral administration of tamoxifen, titers of immunoglobulins, particularly IgG2c and IgE, were increased in Foxp3 flox R26 CreERT2 mice compared with that in controls. Under these conditions, CD4 + T cells from Foxp3 flox R26 CreERT2 mice had increased expression of several activation markers, including inducible costimulator and CD40 ligand, as well as the cytokines interleukin 4 and interferon gamma. In addition, the proportions of T follicular helper (Tfh) cells and germinal center (GC) B cells were increased in Foxp3 flox R26 CreERT2 mice compared with those in controls. These results indicated that Tregs controlled excessive or pathogenic antibody production by suppressing Tfh cell differentiation and GC formation. Furthermore, these data suggested that Foxp3 flox R26 CreERT2 mice could be a useful tool for screening therapeutic agents., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Our previous studies found that mitochondrial uncouplers CCCP and niclosamide inhibited artery constriction and the mechanism involved AMPK activation in vascular smooth muscle cells. BAM15 is a novel type of mitochondrial uncoupler. The aim of the present study is to identify the vasoactivity of BAM15 and characterize the BAM15-induced AMPK activation in vascular smooth muscle cells (A10 cells). BAM15 relaxed phenylephrine (PE)-induced constricted rat mesenteric arteries with intact and denuded endothelium. Pretreatment with BAM15 inhibited PE-induced constriction of rat mesenteric arteries with intact and denuded endothelium. BAM15, CCCP, and niclosamide had the comparable IC 50 value of vasorelaxation in PE-induced constriction of rat mesenteric arteries. BAM15 was less cytotoxic in A10 cells compared with CCCP and niclosamide. BAM15 depolarized mitochondrial membrane potential, induced mitochondrial fission, increased mitochondrial ROS production, and increased mitochondrial oxygen consumption rate in A10 cells. BAM15 potently activated AMPK in A10 cells and the efficacy of BAM15 was stronger than that of CCCP, niclosamide, and AMPK positive activators metformin and AICAR. In conclusion, BAM15 activates AMPK in vascular smooth muscle cells with higher potency than that of CCCP, niclosamide and the known AMPK activators metformin and AICAR. The present work indicates that BAM15 is a potent AMPK activator.

Hexokinase-2 (HK2), the initial as well as the rate-limiting step in glycolysis, is overexpressed in many human cancers, and correlates with poor clinical outcomes. Aerobic glycolysis is a hallmark of cancer, and drugs targeting its enzymes, including HK2, are being developed. However, the mechanisms of HK2 inhibition and the physiological significance of the HK2 inhibitors in cancer cells are rarely reported. Here, we show that microRNA-216a-5p (miR-216a-5p) inhibits HK2 expression by directly targeting its 3'-UTR in uveal melanoma cells. Through inhibition of HK2, miR-216a-5p dampens glycolysis by reducing HK activity, glucose uptake, lactate production, ATP generation, extracellular acidification rate (ECAR), and increasing oxygen consumption rate (OCR) in uveal melanoma cells. Importantly, glycolysis regulated by miR-216a-5p is critical for its regulating uveal melanoma tumor growth both in vitro and in vivo. miR-216a-5p expression is negatively correlated with HK2 expression and predicts better outcome in uveal melanoma patients. Our findings provide clues regarding the role of miR-216a-5p as a tumor suppressor in uveal melanoma through the inhibition of HK2. Targeting HK2 through miR-216a-5p could be a promising therapeutic strategy in uveal melanoma., (Copyright © 2018 Elsevier Inc. All rights reserved.)

In recent years, insertion/deletion (InDel) markers have become a promising and useful supporting tool in forensic identification cases and biogeographic research field. In this study, 30 InDel loci were explored to reveal the genetic diversities and genetic relationships between Chinese Xinjiang Hui group and the 25 previously reported populations using various biostatistics methods such as forensic statistical parameter analysis, phylogenetic reconstruction, multi-dimensional scaling, principal component analysis, and STRUCTURE analysis. No deviations from Hardy-Weinberg equilibrium tests were found at all 30 loci in the Chinese Xinjiang Hui group. The observed heterozygosity and expected heterozygosity ranged from 0.1971 (HLD118) to 0.5092 (HLD92), 0.2222 (HLD118) to 0.5000 (HLD6), respectively. The cumulative probability of exclusion and combined power of discrimination were 0.988849 and 0.99999999999378, respectively, which indicated that these 30 loci could be qualified for personal identification and used as complementary genetic markers for paternity tests in forensic cases. The results of present research based on the different methods of population genetic analysis revealed that the Chinese Xinjiang Hui group had close relationships with most Chinese groups, especially Han populations. In spite of this, for a better understanding of genetic background of the Chinese Xinjiang Hui group, more molecular genetic markers such as ancestry informative markers, single nucleotide polymorphisms (SNPs), and copy number variations will be conducted in future studies., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Biogenic manganese oxides (BioMnOx) have attracted considerable attention as active oxidants, adsorbents, and catalysts. This study investigated the characteristics of algae-generated BioMnOx and determined its oxidative activity towards bisphenol A (BPA), an endocrine disrupter. Amorphous nanoparticles with a primary Mn valency of +3 were found in BioMnOx produced by Desmodesmus sp. WR1. The mechanism might be that algal growth created conditions favorable to Mn oxidation through increasing DO and pH. Initial Mn 2+ concentrations of 6, 30, and 50mgL -1 produced a maximum of 5, 13, and 11mgL -1 of BioMnOx, respectively. Mn 2+ -enriched cultures exhibited the highest BPA removal efficiency (∼78%), while controls only reached about 27%. BioMnOx may significantly promote BPA oxidation in algae culture, enhancing the accumulation of substrates for glycosylation. Moreover, continuous BioMnOx increase and Mn 2+ decrease during BPA oxidation confirmed Mn oxide regeneration. In conclusion, Mn oxide formation by microalgae has the potential to be used for environmental remediation., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Pien-Tze-Huang (PZH) is a popular traditional Chinese medicine (TCM) formula in China, but its pharmacokinetics has not been investigated yet. To better study the pharmacokinetic behaviors of PZH, an optimal ultra-performance liquid chromatography with triple quadrupole mass spectrometry (UPLC-MS/MS) method was developed for rapid quantification of six compounds (notoginsenoside R1, ginsenosides Re, Rg1, Rb1, Rd, and muscone) in rat plasma after oral administration of PZH. All analytes were extracted by protein precipitation with acetonitrile and separated on a Waters Acquity Cortecs C18 column within 3.9min, and detected by multiple-reaction monitoring in positive ion mode. This proposed method exhibited good linearity (r≥0.9932) with a lower quantification limits of 0.558-1.566ng/mL for all analytes. The intra- and inter-day precisions were within 8.24%, and the accuracy was within -10.05 to 9.87% for each analyte. The extraction recovery for each analyte ranged from 80.02 to 96.12%. This UPLC-MS/MS method was successfully applied to the pharmacokinetic study for PZH in rats., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Mitochondria are morphologically dynamic organelles which undergo fission and fusion processes. Our previous study found that arterial constriction was always accompanied by increased mitochondrial fission in smooth muscle cells, whereas inhibition of mitochondrial fission in smooth muscle cells was associated with arterial relaxation. Here, we used the typical vasorelaxants, verapamil and phentolamine, to further confirm the coupling between arterial constriction and mitochondrial fission in rat aorta. Results showed that phentolamine but not verapamil induced vasorelaxation in phenylephrine (PE)-induced rat thoracic aorta constriction. Verapamil, but not phentolamine, induced vasorelaxation in high K + (KPSS)-induced rat thoracic aorta constriction. Pre-treatment with phentolamine prevented PE- but not KPSS-induced aorta constriction and pre-treatment with verapamil prevented both PE- and KPSS-induced aorta constriction. Transmission electron microscopy (TEM) results showed that verapamil but not phentolamine inhibited KPSS-induced excessive mitochondrial fission in aortic smooth muscle cells, and verapamil prevented both PE- and KPSS-induced excessive mitochondrial fission in aortic smooth muscle cells. Verapamil inhibited KPSS-induced excessive mitochondrial fission in cultured vascular smooth muscle cells (A10). These results further demonstrate that arterial relaxation is coupled to inhibition of mitochondrial fission in arterial smooth muscle cells.

We previously demonstrated that the typical mitochondrial uncoupler carbonyl cyanide m-chlorophenylhydrazone (CCCP) inhibited artery constriction, but CCCP was used only as a pharmacological tool. Niclosamide is an anthelmintic drug approved by FDA. Niclosamide ethanolamine (NEN) is a salt form of niclosamide and has been demonstrated to uncouple mitochondrial oxidative phosphorylation. The aim of the present study was to elucidate the vasoactivity of NEN and the potential mechanisms. Isometric tension of rat mesenteric artery and thoracic aorta was recorded by using multi-wire myograph system. The protein levels were measured by using western blot techniques. Niclosamide ethanolamine (NEN) treatment relaxed phenylephrine (PE)- and high K + (KPSS)-induced constriction, and pre-treatment with NEN inhibited PE- and KPSS-induced constriction of rat mesenteric arteries. In rat thoracic aorta, NEN also showed antagonism against PE- and KPSS-induced constriction. NEN induced increase of cellular ADP/ATP ratio in vascular smooth muscle cells (A10) and activated AMP-activated protein kinase (AMPK) in A10 cells and rat thoracic aorta. NEN-induced aorta relaxation was attenuated in AMPKα1 knockout (-/-) mice. SERCA inhibitors cyclopiazonic acid and thapsigargin, but not K ATP channel blockers glibenclamide and 5-hydroxydecanoic acid, attenuated NEN-induced vasorelaxation in rat mesenteric arteries. NEN treatment increased cytosolic [Ca 2+ ] i and depolarized mitochondrial membrane potential in vascular smooth muscle cells (A10). Niclosamide in non-salt form showed the similar vasoactivity as NEN in rat mesenteric arteries. Niclosamide ethanolamine inhibits artery constriction, indicating that it would be promising to be developed as an anti-hypertensive drug or it would induce vasodilation-related side effects when absorbed in vivo., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Transducin-Like Enhancer of Split protein 4 (TLE4) has been reported to be involved in some subsets of acute myeloid leukemia and colorectal cancer. In the present study, we aimed to explore the role of TLE4 in tumorigenesis and cancer progression in hepatocellular carcinoma (HCC)., Methods: The expression pattern of TLE4 in HCC was determined by Western-blot and qRT-PCR, gain-of-function and loss-of-function was used to explore the biological role of TLE4 in HCC cells. A xenograft model was established to confirm its effects on proliferation., Results: The protein expression levels of TLE4 were significantly down-regulated in HCC tissues compared to matched adjacent normal liver tissues. In vitro, down-regulation of TLE4 in Huh7 or SMMC-7721 promoted cell proliferation and ectopical expression of TLE4 in Hep3B or Bel-7404 suppressed cell proliferation. In addition, the cell colony formation ability was enhanced after down-regulation of TLE4 expression in Huh-7 but suppressed after over-expression in Hep3B. Furthermore, down-regulation of TLE4 increased the cell invasion ability, as well as increased the expression level of Vimentin and decreased that of E-cadherin, indicating a phenotype of epithelial-mesenchymal transition (EMT) in HCC cells. On the contrary, ectopical expression of TLE4 in HCC cells decreased the cell invasion ability and inhibited EMT. In vivo, compared to control group, xenograft tumor volumes were significantly decreased in TLE4 overexpression group., Conclusions: These results demonstrated that TLE4 might play important regulatory roles in cellular proliferation and EMT process in HCC., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Hepatic ischemia reperfusion injury (IRI) is an inevitable clinical problem for liver surgeons. Because microRNAs (miRNAs) participate in various hepatic pathophysiological processes, this study aimed to explore the role and potential mechanism of miR-124 in hepatic IRI., Methods: A liver IRI model was established in rats. The differential expression of miRNAs was detected using microarrays, and the expression of miR-124 was measured by qRT-PCR. A hydrogen peroxide (H2O2)-induced oxidative stress apoptosis model was also established. Cell apoptosis was detected by flow cytometry, and viability was detected by CCK8. The expression of Rab38 was detected by Western blotting and qRT-PCR, and a luciferase reporter assay was used to verify the expression of the miR-124 target gene., Results: The miRNA spectrum changes dramatically after hepatic IRI in rats, and miR-124 is significantly down-regulated after liver IRI. MiR-124 decreases the H2O2-induced apoptosis of human hepatic L02 cells by up-regulating the activation of the AKT pathway. Rab38 is a target gene of miR-124 and is involved in H2O2-induced apoptosis. Interference with the expression of the Rab38 gene can protect hepatic L02 from H2O2-induced apoptosis by increasing the phosphorylation of AKT. These protective effects of miR-124 are attenuated by over-expression of Rab38., Conclusions: Many miRNAs are involved in hepatic IRI in rats, and miR-124 is significantly decreased in this model. MiR-124 significantly decreases the H2O2-induced apoptosis of human hepatic L02 cells by targeting the Rab38 gene and activating the AKT pathway., (Copyright © 2014 Elsevier Inc. All rights reserved.)

In the present study, we evaluated a commonly employed modified Bureau Communautaire de Référence (BCR test) 3-step sequential extraction procedure for its ability to distinguish forms of solid-phase Pb in soils with different sources and histories of contamination. When the modified BCR test was applied to mineral soils spiked with three forms of Pb (pyromorphite, hydrocerussite and nitrate salt), the added Pb was highly susceptible to dissolution in the operationally-defined "reducible" or "oxide" fraction regardless of form. When three different materials (mineral soil, organic soil and goethite) were spiked with soluble Pb nitrate, the BCR sequential extraction profiles revealed that soil organic matter was capable of retaining Pb in more stable and acid-resistant forms than silicate clay minerals or goethite. However, the BCR sequential extraction for field-collected soils with known and different sources of Pb contamination was not sufficiently discriminatory in the dissolution of soil Pb phases to allow soil Pb forms to be "fingerprinted" by this method. It is concluded that standard sequential extraction procedures are probably not very useful in predicting lability and bioavailability of Pb in contaminated soils., (Copyright © 2013 Elsevier B.V. All rights reserved.)