Auxin acts upstream of nitric oxide to regulate cell wall xyloglucan and its aluminium-binding capacity in Arabidopsis thaliana.

MAIN CONCLUSION: Auxin acts upstream of NO through NOA and XXT5 pathways to regulate the binding capacity of the root cell wall to Al. In our previous study, we identified an unknown mechanism by which 1-naphthaleneacetic acid (NAA) decreased the fixation of aluminum (Al) in the cell wall. Here, we observed that external application of the nitric oxide (NO) donor S-nitrosoglutathion (GSNO) increased the inhibition of Al on root elongation. Further analysis indicated that GSNO could induce Al accumulation in the roots and root cell walls, which is consistent with lower xyloglucan content. In comparison to the Columbia-0 (Col-0) wild type (WT), endogenous NO-reduced mutants noa1 (NOA pathway) and nia1nia2 (NR pathway) were more resistant to Al, with lower root Al content, higher xyloglucan content, and more Al accumulation in the root cell walls. By contrast, the xxt5 mutant with reduced xyloglucan content exhibited an Al-sensitive phenotype. Interestingly, Al treatment increased the endogenous auxin and NO levels, and the auxin levels induced under Al stress further stimulated NO production. Auxin application reduced Al retention in hemicellulose and decreased the xyloglucan content, similar to the effects observed with GSNO. In yucca and aux1-7 mutants, exogenous application of NO resulted in responses similar to those of the WT, whereas exogenous auxin had little effect on the noa1 mutant under Al stress. In addition, as auxin had similar effects on the nia1nia2 mutant and the WT, exogenous auxin and NO had little effect on the xxt5 mutant under Al stress, further confirming that auxin acts upstream of NO through NOA and XXT5 pathways to regulate the binding capacity of the root cell wall to Al.

Melatonin Increases Root Cell Wall Phosphorus Reutilization via an NO Dependent Pathway in Rice (Oryza sativa).

Melatonin (MT) has been implicated in the plant response to phosphorus (P) stress; however, the precise molecular mechanisms involved remain unclear. This study investigated whether MT controls internal P distribution and root cell wall P remobilization in rice. Rice was treated with varying MT and P levels and analyzed using biochemical and molecular techniques to study phosphorus utilization. The results demonstrated that low P levels lead to a rapid increase in endogenous MT levels in rice roots. Furthermore, the exogenous application of MT significantly improved rice tolerance to P deficiency, as evidenced by the increased biomass and reduced proportion of roots to shoots under P-deficient conditions. MT application also mitigated the decrease in P content regardless in both the roots and shoots. Mechanistically, MT accelerated the reutilization of P, particularly in the root pectin fraction, leading to increased soluble P liberation. In addition, MT enhanced the expression of OsPT8, a gene involved in root-to-shoot P translocation. Furthermore, we observed that MT induced the production of nitric oxide (NO) in P-deficient rice roots and that the mitigating effect of MT on P deficiency was compromised in the presence of the NO inhibitor, c-PTIO, implying that NO is involved in the MT-facilitated mitigation of P deficiency in rice. Overall, our findings highlight the potential of MT as a promising strategy for enhancing rice tolerance to P deficiency and improving P use efficiency in agricultural practices.

Left main bifurcation stenting: impact of residual ischaemia on cardiovascular mortality.

AIMS: The present study sought to determine the rate and prognostic implications of post-procedural physiologically significant residual ischemia according to Murray law-based quantitative flow ratio (µQFR) after left main (LM) bifurcation percutaneous coronary intervention (PCI). METHODS AND RESULTS: Consecutive patients undergoing LM bifurcation stenting at a large tertiary care center between January 2014 and December 2016 with available post-PCI µQFR were included. Physiologically significant residual ischemia was defined by post-PCI µQFR values ≤0.80 in the left anterior descending (LAD) or left circumflex artery (LCX). The primary outcome was 3-year cardiovascular death. The major secondary outcome was 3-year bifurcation-oriented composite endpoint (BOCE). Among 1170 included patients with analyzable post-PCI µQFR, 155 (13.2%) had residual ischemia in either LAD or LCX. Patients with vs. those without residual ischemia had a higher risk of 3-year cardiovascular mortality [5.4% vs. 1.3%; adjusted hazard ratio (HR) 3.20, 95% confidence interval (CI): 1.16-8.80]. The 3-year risk of BOCE was significantly higher in the residual ischemia group (17.8% vs. 5.8%; adjusted HR 2.79, 95% CI: 1.68-4.64), driven by higher incidence of the composite of cardiovascular death and target bifurcation-related myocardial infarction (14.0% vs. 3.3%; adjusted HR 4.06, 95% CI: 2.22-7.42). A significant, inverse association was observed between continuous post-PCI µQFR and the risk of clinical outcomes (per 0.1 µQFR decrease, HR of cardiovascular death 1.27, 95% CI: 1.00-1.62; HR of BOCE 1.29, 95% CI: 1.14-1.47). CONCLUSION: After angiographically successful LM bifurcation PCI, residual ischemia assessed by µQFR was identified in 13.2% of patients and was associated with higher risk of 3-year cardiovascular death, indicating the superior prognostic value of post-PCI physiological assessment.

High-entropy alloys in electrocatalysis: from fundamentals to applications.

High-entropy alloys (HEAs) comprising five or more elements in near-equiatomic proportions have attracted ever increasing attention for their distinctive properties, such as exceptional strength, corrosion resistance, high hardness, and excellent ductility. The presence of multiple adjacent elements in HEAs provides unique opportunities for novel and adaptable active sites. By carefully selecting the element configuration and composition, these active sites can be optimized for specific purposes. Recently, HEAs have been shown to exhibit remarkable performance in electrocatalytic reactions. Further activity improvement of HEAs is necessary to determine their active sites, investigate the interactions between constituent elements, and understand the reaction mechanisms. Accordingly, a comprehensive review is imperative to capture the advancements in this burgeoning field. In this review, we provide a detailed account of the recent advances in synthetic methods, design principles, and characterization technologies for HEA-based electrocatalysts. Moreover, we discuss the diverse applications of HEAs in electrocatalytic energy conversion reactions, including the hydrogen evolution reaction, hydrogen oxidation reaction, oxygen reduction reaction, oxygen evolution reaction, carbon dioxide reduction reaction, nitrogen reduction reaction, and alcohol oxidation reaction. By comprehensively covering these topics, we aim to elucidate the intricacies of active sites, constituent element interactions, and reaction mechanisms associated with HEAs. Finally, we underscore the imminent challenges and emphasize the significance of both experimental and theoretical perspectives, as well as the potential applications of HEAs in catalysis. We anticipate that this review will encourage further exploration and development of HEAs in electrochemistry-related applications.

[Effect of Xiongcan Yishen Formula on ferroptosis in mouse TM3 Leydig cells after oxidative stress injury].

OBJECTIVE: To investigate the effects of Xiongcan Yishen Formula (XYF) on ferroptosis in mouse TM3 Leydig cells after oxidative stress injury (OSI) induced by H2O2.　Methods: An oxidative stress injury model was established in mouse TM3 Leydig cells using H2O2 induction. The modeled TM3 cells were randomly divided into OSI group, XYF group, the ferroptosis inhibitor Ferrostatin-1 (F-1) group, and F-1+XYF group, which were respectively intervened with blank serum, 20% drug-containing serum, 2µmol/L F-1, and 2µmol/L F-1+ 20% drug-containing serum. A control group (normal TM3 cells + blank serum) was also set up. The morphology of cells in each group was observed, and the levels of testosterone, superoxide dismutase (SOD), reactive oxygen species (ROS), malondialdehyde (MDA), ferritin heavy chain 1 (FTH1), solute carrier family 7 member 11 (SLC7A11), glutathione (GSH), glutathione peroxidase 4 (GPX4), fatty acid CoA ligase 4 (FACL4), total iron ions, and ferrous ions were detected. RESULTS: Compared with the model group, the control group showed significantly decreased expression of ROS, MDA, FACL4, total iron, and ferrous ions (P<0.05), and significantly increased levels of testosterone, SOD, GSH, FTH1, SLC7A11, and GPX4 (P<0.05). The male silkworm kidney-tonifying formula group significantly promoted testosterone secretion by TM3 cells and upregulated the expression of FTH1, SLC7A11, GPX4, GSH, and SOD in TM3 cells (P<0.05), while significantly downregulating ROS, MDA, FACL4, total iron ions, and ferrous ions (P<0.05). CONCLUSION: Following H2O2 exposure, oxidative stress can induce ferroptosis in mouse TM3 Leydig cells. XYF can antagonize OSI and ferroptosis in TM3 cells by activating the SLC7A11/GSH/GPX4 axis, which may underlie the mechanism of XYF in the treatment of male late-onset hypogonadism.

Interface Metal Oxides Regulating Electronic State around Nickel Species for Efficient Alkaline Hydrogen Electrocatalysis.

Heterogeneous electrocatalysis typically depends on the surface electronic states of active sites. Modulating the surface charge state of an electrocatalysts can be employed to improve performance. Among all the investigated materials, nickel (Ni)-based catalysts are the only non-noble-metal-based alternatives for both hydrogen oxidation and evolution reactions (HOR and HER) in alkaline electrolyte, while their activities should be further improved because of the unfavorable hydrogen adsorption behavior. Hereto, Ni with exceptional HOR electrocatalytic performance by changing the d-band center by metal oxides interface coupling formed in situ is endowed. The resultant MoO2 coupled Ni heterostructures exhibit an apparent HOR activity, even approaching to that of commercial 20% Pt/C benchmark, but with better long-term stability in alkaline electrolyte. An exceptional HER performance is also achieved by the Ni-MoO2 heterostructures. The experiment results are rationalized by the theoretical calculations, which indicate that coupling MoO2 with Ni results in the downshift of d-band center of Ni, and thus weakens hydrogen adsorption and benefits for hydroxyl adsorption. This concept is further proved by other metal oxides (e.g., CeO2 , V2 O3 , WO3 , Cr2 O3 )-formed Ni-based heterostructures to engineer efficient hydrogen electrocatalysts.

Rational Synthesis of Core-Shell-Structured Nickel Sulfide-Based Nanostructures for Efficient Seawater Electrolysis.

Versatile electrocatalysis at higher current densities for natural seawater splitting to produce hydrogen demands active and robust catalysts to overcome the severe chloride corrosion, competing chlorine evolution, and catalyst poisoning. Hereto, the core-shell-structured heterostructures composed of amorphous NiFe hydroxide layer capped Ni3 S2 nanopyramids which are directly grown on nickel foam skeleton (NiS@LDH/NF) are rationally prepared to regulate cooperatively electronic structure and mass transport for boosting oxygen evolution reaction (OER) performance at larger current densities. The prepared NiS@LDH/NF delivers the anodic current density of 1000 mA cm-2 at the overpotential of 341 mV in 1.0 m KOH seawater. The feasible surface reconstruction of Ni3 S2 -FeNi LDH interfaces improves the chemical stability and corrosion resistance, ensuring the robust electrocatalytic activity in seawater electrolytes for continuous and stable oxygen evolution without any hypochlorite production. Meanwhile, the designed Ni3 S2 nanopyramids coated with FeNi2 P layer (NiS@FeNiP/NF) still exhibit the improved hydrogen evolution reaction (HER) activity in 1.0 m KOH seawater. Furthermore, the NiS@FeNiP/NF||NiS@LDH/NF pair requires cell voltage of 1.636 V to attain 100 mA cm-2 with a 100% Faradaic efficiency, exhibiting tremendous potential for hydrogen production from seawater.

Enabling Internal Electric Field in Heterogeneous Nanosheets to Significantly Accelerate Alkaline Hydrogen Electrocatalysis.

Efficient bifunctional hydrogen electrocatalysis, encompassing both hydrogen evolution reaction (HER) and hydrogen oxidation reaction (HOR), is of paramount significance in advancing hydrogen-based societies. While non-precious-metal-based catalysts, particularly those based on nickel (Ni), are essential for alkaline HER/HOR, their intrinsic catalytic activity often falls short of expectations. Herein, an internal electric field (IEF) strategy is introduced for the engineering of heterogeneous nickel-vanadium oxide nanosheet arrays grown on porous nickel foam (Ni-V2 O3 /PNF) as bifunctional electrocatalysts for hydrogen electrocatalysis. Strikingly, the Ni-V2 O3 /PNF delivers 10 mA cm-2 at an overpotential of 54 mV for HER and a mass-specific kinetic current of 19.3 A g-1 at an overpotential of 50 mV for HOR, placing it on par with the benchmark 20% Pt/C, while exhibiting enhanced stability in alkaline electrolytes. Density functional theory calculations, in conjunction with experimental characterizations, unveil that the interface IEF effect fosters asymmetrical charge distributions, which results in more thermoneutral hydrogen adsorption Gibbs free energy on the electron-deficient Ni side, thus elevating the overall efficiency of both HER and HOR. The discoveries reported herein guidance are provided for further understanding and designing efficient non-precious-metal-based electrocatalysts through the IEF strategy.

Optical force conversion and conveyor belt effect with coupled graphene plasmon waveguide modes.

We propose a double-layer graphene sheets side coupling to a strip of graphene to obtain the optical pulling or pushing force. Combined with coupled mode theory and finite-difference time-domain simulations, it is found that the conveyor belt effect can be realized in conjunction with the lateral optical equilibrium effect upon the radiation loss κe equal to the intrinsic loss κo. The maximum total optical force acting on the strip in the symmetric mode (S-mode) can be up to ∼5.95 in the unit of 1/c and the anti-symmetric (AS-mode) mode reach ∼2.75 1/c. The optical trapping potential Ux and optical trapping force Fx for the S-mode have a value around -22.5 kBT/W and 240 pN/W, while for the AS-mode can up to ∼-56 kBT/W and 520 pN/W, respectively. Our work opens a new avenue for optical manipulation with potential applications in optoelectronic devices and lab-on-a-chip platforms.

Feasibility and Safety of Drug-Coated Balloon for Treatment of De Novo Coronary Artery Lesions in Large Vessel Disease: A Large-Scale Multicenter Prospective Study.

Background: Drug-coated balloons (DCB) have been evaluated to be safe and practical in treating coronary small vessel disease (SVD). However, evidence about the practicality and safety of DCB in treating coronary lesions with diameters greater than 3.0 mm is limited. Methods: 1166 patients who received DCB angioplasty were enrolled and divided into groups of SVD or large vessel disease (LVD) according to the target vessel diameters ( < 3.0 mm for SVD; ≥ 3.0 mm for LVD). All participants received a 2-year follow-up. The two main outcomes were patient-oriented composite endpoint (patient-oriented composite endpoint (POCE), all-cause mortality, all myocardial infarctions [MI], or any revascularization), and target lesion failure (target lesion failure (TLF), cardiac death, target vessel MI, or ischemia-driven target lesion revascularization). Results: In these patients, a total of 30 (2.6%) TLF and 82 (7.0%) POCE were recorded. Patients in the LVD group showed statistically greater rates of lesion success compared to the SVD group (752 [96.0%] vs. 380 [99.2%], p = 0.004) and procedural success (751 [95.9%] vs. 380 [99.2%], p = 0.003). No significant difference was found in the 2-year risk of TLF (hazard ratio (HR) 1.41, 95% CI 0.58-3.44; p = 0.455), POCE (HR 1.29, 95% CI 0.76-2.20; p = 0.354), MI (HR 0.88, 95% CI 0.24-3.13; p = 0.837), revascularization (HR 1.22, 95% CI 0.68-2.21; p = 0.506), and stroke (HR 0.78, 95% CI 0.03-15.26; p = 0.784) between the SVD and LVD groups. Conclusions: There was no discernible inferiority of the DCB intervention in the LVD group as compared to the SVD group. The DCB intervention is practical for coronary lesions with diameters higher than 3.0 mm.

Atranorin inhibits NLRP3 inflammasome activation by targeting ASC and protects NLRP3 inflammasome-driven diseases.

Aberrant NLRP3 activation has been implicated in the pathogenesis of numerous inflammation-associated diseases. However, no small molecular inhibitor that directly targets NLRP3 inflammasome has been approved so far. In this study, we show that Atranorin (C19H18O8), the secondary metabolites of lichen family, effectively prevents NLRP3 inflammasome activation in macrophages and dendritic cells. Mechanistically, Atranorin inhibits NLRP3 activation induced cytokine secretion and cell pyroptosis through binding to ASC protein directly and therefore restraining ASC oligomerization. The pharmacological effect of Atranorin is evaluated in NLRP3 inflammasome-driven disease models. Atranorin lowers serum IL-1ß and IL-18 levels in LPS induced mice acute inflammation model. Also, Atranorin protects against MSU crystal induced mice gouty arthritis model and lowers ankle IL-1ß level. Moreover, Atranorin ameliorates intestinal inflammation and epithelial barrier dysfunction in DSS induced mice ulcerative colitis and inhibits NLRP3 inflammasome activation in colon. Altogether, our study identifies Atranorin as a novel NLRP3 inhibitor that targets ASC protein and highlights the potential therapeutic effects of Atranorin in NLRP3 inflammasome-driven diseases including acute inflammation, gouty arthritis and ulcerative colitis.

Independent-effect comparison of five crosslinking procedures for Progressive Keratoconus based on Keratometry and the ABCD Grading System using Generalized Estimating Equations (GEE).

PURPOSE: Corneal collagen crosslinking (CXL) is an effective treatment for progressive keratoconus. Multiple CXL modalities are clinically available. The present study compared the 1 year outcomes of five types of CXL procedures for progressive keratoconus in a Chinese population using generalized estimating equations (GEE). METHODS: This retrospective study included 239 eyes in 171 patients with keratoconus who underwent CXL and were followed up for 1 year. Five CXL procedures were assessed, including Accelerated Transepithelial CXL, Iontophoresis CXL for 10 min, CXL plus phototherapeutic keratectomy (CXL-plus-PTK), High-Fluence Accelerated CXL, and Accelerated CXL. Patients treated with the Accelerated CXL procedure represented the reference group. Primary outcomes were visual acuity change, spherical equivalence, endothelial cell density, mean keratometry (Kmean), maximum keratometry (Kmax), minimum corneal thickness (MCT), and the ABCD Grading System, consisting of A (staging index for ARC; ARC = anterior radius of curvature), B (staging index for PRC, PRC = posterior radius of curvature), and C (staging index for MCT) values 1 year postoperatively compared to baseline. Secondary outcomes were corrected GEE comparisons from each procedure versus the Accelerated CXL group. RESULTS: The Accelerated Transepithelial CXL group had lower performance than the Accelerated CXL group according to Kmean and Kmax. The CXL-plus-PTK group performed significantly better than the reference group as reflected by Kmax (ß = -0.935, P = 0.03). However, the CXL-plus-PTK group did not perform as well for B and C, and the Iontophoresis CXL group performed better for C. CONCLUSIONS: The CXL-plus-PTK procedure was more effective than the Accelerated CXL procedure based on Kmax, and the Iontophoresis CXL procedure performed better on the C value based on the ABCD Grading System.

[Xiongcan Yishen Formula up-regulates the clock gene expressions in the testis tissue of the rats with late-onset hypogonadism].

OBJECTIVE: To investigate the effect of Xiongcan Yishen Formula (XYF) on the expressions of the clock genes in the testis tissue of the rats with late-onset hypogonadism (LOH). METHODS: Forty-eight 8-week-old male SD rats were randomly divided into 6 groups, normal control, model control, testosterone propionate (TP), and low-, medium- and high-dose XYF. The LOH model was made in the later 5 groups of rats by intraperitoneal injection of D-galactose at 480 mg/kg/d for 56 successive days, while the normal controls were injected with the same volume of normal saline. After modeling, the rats in the low-, medium- and high-dose XYF groups were treated intragastrically with XYF at 10.4, 20.8 and 41.6 g/kg/d, bid, respectively, those in the normal and model control groups with the same volume of distilled water, and those in the TP group intramuscularly with TP at 5.21 mg/kg/d, qd alt, all for 28 days. After treatment, the supernatant was obtained for measurement of the serum T level by ELISA, and the testis tissue collected for determination of the mRNA and protein expressions of BMAL1, NR1D1, PER2, CRY1, StAR and CYP11A1 by RT-qPCR and Western blot. RESULTS: Compared with the normal controls, the rats in the LOH model control group showed significantly decreased serum T and mRNA and protein expressions of BMAL1, NR1D1, PER2, CRY1, StAR and CYP11A1 (P < 0.05). In comparison with the findings in the model controls, the T level was remarkably increased in the TP and XYF groups (P < 0.05), the expressions of StAR mRNA and CYP11A1 mRNA and protein markedly up-regulated in the high-dose XYF group (P < 0.05), and so was the expression of the StAR protein in the XYF and TP groups (P < 0.05), those of BMAL1 and NR1D1 proteins and PER2 mRNA and protein in the high-dose XYF group (P < 0.05), those of BMAL1 mRNA and CRY1 protein in the medium- and high-dose XYF groups (P < 0.05), that of NR1D1 mRNA in the XYF and TP groups (P < 0.05), and that of CRY1 mRNA in the medium- and high-dose XYF and TP groups (P < 0.05). CONCLUSION: Xiongcan Yishen Formula could up-regulate the expressions of the clock genes in the testis tissue of the LOH rats and increase the serum T level as well, which may underlie the mechanisms of Xiongcan Yishen Formula acting on LOH.

Effect of Thin-Walled Radial Sheath for Large-Bore Access On Reducing Periprocedural Radial Artery Occlusion Following Complex PCI: The REDUCE-RAO Randomized Trial.

Background: Transradial artery (TRA) access for percutaneous coronary intervention (PCI) was associated with lower risks of major bleeding and vascular complications compared to transfemoral artery access. Use of large-bore ( ≥ 7-Fr) guiding catheters through TRA approach increased the likelihood of radial artery occlusion (RAO). This study aimed to investigate whether use of the thin-walled 7-Fr Glidesheath Slender, allowing PCI with large-caliber guiding catheters, is superior to standard 7-Fr Cordis sheath with respect to periprocedural RAO within 24 hours after transradial coronary intervention (TRI) in complex lesions. Methods: A prospective randomized, controlled, single-blinded (patient-blinded) trial was conducted, randomizing 504 patients with TRI for complex lesions to either 7-Fr Glidesheath Slender or conventional 7-Fr Cordis sheath. The primary outcome was defined as the incidence of periprocedural RAO with Doppler ultrasound during the first 24 hours after TRI. Results: The incidence of early RAO was 10.3% for 7-Fr Glidesheath Slender and 13.5% for conventional 7-Fr sheath (p = 0.271). The procedural success rate for Glidesheath Slender was 92.9% and for Cordis sheath was 93.7% (p = 0.722). There was no signficiant difference between treatment arms in terms of local hematoma and radial spasm, whereas use of the Glidesheath Slender was associated with significantly less pain during the procedure (numeric rating scale [NRS], 2.27 ± 0.75 vs. 2.45 ± 0.95, p = 0.017). The assessment of radial artery in ultrasound parameters after complex TRI was improved with Glidesheath Slender. Conclusions: Among patients with complex coronary lesions undergoing TRI, 7-Fr Glidesheath Slender was not superior to conventional 7-Fr in the prevention of periprocedural RAO within 24 hours following complex PCI, without reducing RAO occurrence. Clinical Trial Registration: NCT04748068.

Establishing the optimal duration of DAPT following PCI in high-risk TWILIGHT-like patients with acute coronary syndrome.

OBJECTIVES: To determine the association of extended-term (>12-month) versus short-term dual antiplatelet therapy (DAPT) with ischemic and hemorrhagic events in high-risk "TWILIGHT-like" patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) in clinical practice. BACKGROUND: Recent emphasis on shorter DAPT regimen after PCI irrespective of indication for PCI may fail to account for the substantial residual risk of recurrent atherothrombotic events in ACS patients. METHODS: All consecutive patients fulfilling the "TWILIGHT-like" criteria undergoing PCI were identified from the prospective Fuwai PCI Registry. High-risk patients (n = 8,358) were defined by at least one clinical and one angiographic feature based on TWILIGHT trial selection criteria. The primary ischemic endpoint was major adverse cardiac and cerebrovascular events at 30 months, composed of all-cause mortality, myocardial infarction, or stroke while BARC type 2, 3, or 5 bleeding was key secondary outcome. RESULTS: Of 4,875 high-risk ACS patients who remained event-free at 12 months after PCI, DAPT>12-month compared with shorter DAPT reduced the primary ischemic endpoint by 63% (1.5 vs. 3.8%; HRadj: 0.374, 95% CI: 0.256-0.548; HRmatched: 0.361, 95% CI: 0.221-0.590). The HR for cardiovascular death was 0.049 (0.007-0.362) and that for MI 0.45 (0.153-1.320) and definite/probable stent thrombosis 0.296 (0.080-1.095) in propensity-matched analyses. Rates of BARC type 2, 3, or 5 bleeding (0.9 vs. 1.3%; HRadj: 0.668 [0.379-1.178]; HRmatched: 0.721 [0.369-1.410]) did not differ significantly between two groups. CONCLUSIONS: Among high-risk ACS patients undergoing PCI, long-term DAPT, compared with shorter DAPT, reduced ischemic events without a concomitant increase in clinically meaning bleeding events, suggesting that prolonged DAPT can be considered in ACS patients who present with a particularly higher risk for thrombotic complications without excessive risk of bleeding.

The effects of estrogen on targeted cancer therapy drugs.

Improving the efficacy of anticancer drugs is especially challenging. Estrogen is a sex hormone that not only promotes the development of female secondary sexual characteristics, but also supports many important physiological functions. Interestingly, estrogen has shown to be vital for the activity of some anticancer drugs, such as adriamycin, cisplatin, olaparib, trastuzumab, bevacizumab, tamoxifen, cyclophosphamide, methotrexate, and paclitaxel. Although there are many reasons for the differences in therapeutic effects among cancer patients, estrogen status is undoubtedly a very important factor. In view of the importance of the crosstalk between estrogen signaling and drug therapy for cancer, this review summarizes the effects of estrogen on the targets, metabolism and resistance of anticancer drugs and describes the related pathways and underlying mechanisms. Here, an analysis of the close relationship between estrogen and cancer drug therapy was conducted to clarify the effects of estrogen on the therapeutic efficacy of anticancer drugs to facilitate the future development of specific drug treatment strategies to achieve optimal outcomes.

Thrombotic vs. Bleeding Events of Interruption of Dual Antiplatelet Therapy within 12 Months among Patients with Stent-Driven High Ischemic Risk Definition following PCI.

BACKGROUND: There is a paucity of real-world data regarding the clinical impact of dual antiplatelet therapy (DAPT) interruption (temporary or permanent) among patients at high ischemic risk. The aim of this study was to assess the risk of cardiovascular events after interruption of DAPT in high-risk PCI population. METHODS: This study used data from the Fuwai PCI registry, a large, prospective cohort of consecutive patients who underwent PCI. We assessed 3,931 patients with at least 1 high ischemic risk criteria of stent-related recurrent ischemic events proposed in the 2017 ESC guidelines for focused update on DAPT who were free of major cardiac events in the first 12 months. The primary ischemic endpoint was 30-month major adverse cardiac and cerebrovascular events, and the key safety endpoints were BARC class 2, 3, or 5 bleeding and net adverse clinical events. RESULTS: DAPT interruption within 12 months occurred in 1,122 patients (28.5%), most of which were due to bleeding events or patients' noncompliance to treatment. A multivariate Cox regression model, propensity score (PS) matching, and inverse probability of treatment weighting (IPTW) based on the propensity score demonstrated that DAPT interruption significantly increased the risk of primary ischemic endpoint compared with prolonged DAPT (3.9% vs. 2.2%; Cox-adjusted hazard ratio (HR): 1.840; 95% confidence interval (CI): 1.247 to 2.716; PS matching-HR: 2.049 [1.236-3.399]; IPTW-adjusted HR: 1.843 [1.250-2.717]). This difference was driven mainly by all-cause death (1.8% vs. 0.7%) and MI (1.3% vs. 0.5%). Furthermore, the rate of net adverse clinical events (4.9% vs. 3.2%; Cox-adjusted HR: 1.581 [1.128-2.216]; PS matching-HR: 1.639 [1.075-2.499]; IPTW-adjusted HR: 1.554 [1.110-2.177]) was also higher in patients with DAPT interruption (≤12 months), whereas no significant differences between groups were observed in terms of BARC 2, 3, or 5 bleeding. These findings were consistent across various stent-driven high-ischemic risk subsets with respect to the primary ischemic endpoints, with a greater magnitude of harm among patients with diffuse multivessel diabetic coronary artery disease. CONCLUSIONS: In patients undergoing high-risk PCI, interruption of DAPT in the first 12 months occurred infrequently and was associated with a significantly higher adjusted risk of major adverse cardiovascular events and net adverse clinical events. 2017 ESC stent-driven high ischemic risk criteria may help clinicians to discriminate patient selection in the use of long-term DAPT when the ischemic risk certainly overcomes the bleeding one.

A Convenient Procedure for Preparing BiOX-TiO2 Photoelectrocatalytic Electrodes from a Titanium-Oxo Compound-Modified Carbon Fiber Cloth.

Photoelectrocatalysis (PEC) has shown great advantages in sustainable organic synthesis and wastewater treatment because the PEC process can minimize electron-hole recombination, thereby improving the photocatalytic performance. Here, we report a convenient procedure for preparing immobilized BiOX-TiO2 photoelectrocatalytic electrodes from a titanium-oxo compound (TOC)-modified carbon fiber cloth (CFC). Crystalline TOCs composed of Ti12 cations and bismuth halide anions, [Ti12O14(OiPr)18][Bi3Br11(THF)2] (1) and [Ti12O14(OiPr)18][Bi4I14(THF)2] (2), were grown on CFC. Taking advantage of the easy hydrolysis of the titanium-oxo cation and bismuth halide anion, we could easily transform these CFC-immobilized crystals into BiOX-TiO2/CFC (X = Br or I) photocatalysts, which facilitates recycling of the catalysts. The photocatalytic dye degradation test showed that the efficiency did not decrease obviously after 10 photocatalytic cycles. Using BiOX-TiO2-modified CFC as electrodes, electrocatalysis (EC), photocatalysis (PC), and PEC were examined. PEC showed an attractive synergistic effect of EC and PC. These TOC-modified CFCs would be potential candidates for catalytic electrodes for sustainable wastewater purification.

STING inhibitor ameliorates LPS-induced ALI by preventing vascular endothelial cells-mediated immune cells chemotaxis and adhesion.

Acute lung injury (ALI) is a common and devastating clinical disorder featured by excessive inflammatory responses. Stimulator of interferon genes (STING) is an indispensable molecule for regulating inflammation and immune response in multiple diseases, but the role of STING in the ALI pathogenesis is not well elucidated. In this study, we explored the molecular mechanisms of STING in regulating lipopolysaccharide (LPS)-induced lung injury. Mice were pretreated with a STING inhibitor C-176 (15, 30 mg/kg, i.p.) before LPS inhalation to induce ALI. We showed that LPS inhalation significantly increased STING expression in the lung tissues, whereas C-176 pretreatment dose-dependently suppressed the expression of STING, decreased the production of inflammatory cytokines including TNF-α, IL-6, IL-12, and IL-1ß, and restrained the expression of chemokines and adhesion molecule vascular cell adhesion protein-1 (VCAM-1) in the lung tissues. Consistently, in vitro experiments conducted in TNF-α-stimulated HMEC-1cells (common and classic vascular endothelial cells) revealed that human STING inhibitor H-151 or STING siRNA downregulated the expression levels of adhesion molecule and chemokines in HMEC-1cells, accompanied by decreased adhesive ability and chemotaxis of immunocytes upon TNF-α stimulation. We further revealed that STING inhibitor H-151 or STING knockdown significantly decreased the phosphorylation of transcription factor STAT1, which subsequently influenced its binding to chemokine CCL2 and adhesive molecule VCAM-1 gene promoter. Collectively, STING inhibitor can alleviate LPS-induced ALI in mice by preventing vascular endothelial cells-mediated immune cell chemotaxis and adhesion, suggesting that STING may be a promising therapeutic target for the treatment of ALI.

[Establishment and evaluation of a rat model of late-on-set hypogonadism using D-galactose].

OBJECTIVE: To explore the feasibility and duration of establishing a model of late-on-set hypogonadism (LOH) in rats using D-galactose (D-gal) and the optimal concentration of D-gal in modeling. METHODS: Thirty-five 8-week-old male SD rats were randomly divided into seven groups of an equal number to receive intraperitoneal injection of normal saline (normal control) or D-gal at 480 mg/kg/d (high-dose), 240 mg/kg/d (medium-dose) and 120 mg/kg/d (low-dose) for 6 or 8 weeks respectively. Another five 18-month-old SD rats were taken as positive controls. After modeling, the animals were subjected to tail suspension test and mating test, weighed, and then sacrificed for examination of the levels of fasting blood glucose (FBG) and serum testosterone (T), testis index and semen parameters, determination of the expressions of the BMAL1 and NR1D1 proteins in the testis tissue by Western blot, and observation of the pathological and ultrastructural changes in the testis tissue under the light microscope and transmission electron microscope. RESULTS: Compared with the normal controls, the serum T level was significantly decreased in the 6-week medium-dose D-gal (6WMD), 6-week high-dose D-gal (6WHD), 8WMD, 8WHD and positive control groups (P < 0.05), and so were sperm concentration and the percentage of progressively motile sperm (PMS) in the 8WHD and positive control groups (P < 0.05), and the numbers of captures and ejaculations in all the model rats and positive controls (P < 0.05), while the body weight was markedly increased in the 8-week low-dose D-gal (8WLD), 8WMD and 8WHD groups (P < 0.05), and so were the tail suspension time in the 6WHD, 8WHD, 8WMD, 8WLD and positive control groups (P < 0.05) and the FBG level in all the model rats and positive controls (P < 0.05). The expression of the BMAL1 protein was significantly decreased in the 6WHD, 8WLD, 8WMD, 8WHD and positive control groups (P < 0.05), and so was that of NR1D1 in the 8WMD, 8WHD and positive control groups (P < 0.05). Compared with the positive controls, no statistically significant differences were observed in the serum T level in the 6WHD and 8WHD groups (P > 0.05), the testis index in the 8WMD and 8WHD groups (P > 0.05), sperm concentration, percentage of FMS, time of tail suspension and numbers of captures and ejaculations in the 8WHD group (P > 0.05), the level of FBG in the 6WMD, 6WHD, 8WLD, 8WMD and 8WHD groups (P > 0.05), the expression of BMAL1 in the 6WHD, 8WLD, 8WMD and 8WHD groups (P > 0.05), and that of NR1D1 in the 6WLD, 8WMD and 8WHD groups (P > 0.05). Pathological and ultrastructural changes in the testis tissue were observed in all the model rats and positive controls, most significantly in the 8WHD and positive control groups. CONCLUSION: It is feasible to establish an LOH model in male SD rats by intraperitoneal injection of D-gal, most recommendably at the centration of 480 mg/kg/d for 8 weeks.