Effects of carrimycin on biomarkers of inflammation and immune function in tumor patients with sepsis: A multicenter double-blind randomized controlled trial.

Carrimycin is a potential immune-regulating agent for sepsis in patients with tumors. In this study, we investigated its effects on inflammation and immune function in tumor patients with sepsis. In total, 120 participants were randomized to receive either carrimycin treatment (400 mg/day) (n = 62) or placebo (n = 58) for 7 days. The primary outcomes were immune-related indicators. Subsequently, patients were stratified into two subgroups (CD4 < 38.25% and CD8 < 25.195%). Ninety-nine participants were analyzed: 47 and 52 in the carrimycin and placebo groups, respectively. HLA-DR levels were rapidly increased in the carrimycin group; however, the placebo group initially experienced a decline in HLA-DR level at 1 day after administration. In the subgroup with CD4 < 38.25%, the carrimycin group exhibited significantly higher HLA-DR levels than the placebo group (2.270, P = 0.023) 1 day after administration and the degree of increase in HLA-DR in the carrimycin group was higher than that in the placebo group (2.057, P = 0.040). In the CD8 < 25.195% subgroup, the carrimycin group demonstrated significantly higher levels of CD8+ T cells than the placebo group at 3 (2.300,P = 0.027) and 5 (2.106, P = 0.035) days after administration. Carrimycin intervention led to significant reductions in the SOFA, APACHE II, PCT, and CRP levels. No adverse events were observed. In tumor patients with sepsis, particularly in those experiencing immunological suppression, carrimycin effectively regulates immune responses by increasing HLA-DR and CD8+ T cell levels and plays an anti-infective role, reducing disease severity. (Chictr.org.cn, ID Number: ChiCTR2000032339).

Intramolecular hydrogen bonds quench photoluminescence and enhance photocatalytic activity of carbon nanodots.

Understanding the photoluminescence (PL) and photocatalytic properties of carbon nanodots (CNDs) induced by environmental factors such as pH through surface groups is significantly important to rationally tune the emission and photodriven catalysis of CNDs. Through adjusting the pH of an aqueous solution of CNDs, it was found that the PL of CNDs prepared by ultrasonic treatment of glucose is strongly quenched at pH 1 because of the formation of intramolecular hydrogen bonds among the oxygen-containing surface groups. The position of the strongest PL peak and its corresponding excitation wavelength strongly depend on the surface groups. The origins of the blue and green emissions of CNDs are closely related to the carboxyl and hydroxyl groups, respectively. The deprotonated COO(-) and CO(-) groups weaken the PL peak of the CNDs and shift it to the red. CNDs alone exhibit photocatalytic activity towards degradation of Rhodamine B at different pH values under UV irradiation. The photocatalytic activity of the CNDs is the highest at pH 1 because of the strong intramolecular hydrogen bonds formed among the oxygen-containing groups.

Multifunctional Nitrogen-Doped Carbon Nanodots for Photoluminescence, Sensor, and Visible-Light-Induced H2 Production.

Herein, multifunctional N-doped carbon nanodots (NCNDs) were prepared through the one-step hydrothermal treatment of yeast. Results show that the NCNDs can be used as a new photocatalyst to drive the water-splitting reaction under UV light. Moreover, the NCNDs can efficiently catalyze the hydrogen evolution reaction. Under visible-light irradiation, Eosin Y-sensitized NCNDs exhibit excellent activity for hydrogen evolution. The hydrogen evolution rate of NCNDs (without any modification and co-catalyst) reaches 107.1 µmol h(-1) (2142 µmol g(-1) h(-1) ). When Pt is loaded on the NCNDs, the hydrogen evolution rate reaches 491.2 µmol h(-1) (9824 µmol g(-1) h(-1)) under visible-light irradiation. In addition, the NCNDs show excellent fluorescent properties and can be applied as a fluorescent probe for the sensitive and selective detection of Fe(3+) .

A Comparison of Fentanyl and Flurbiprofen Axetil on Serum VEGF-C, TNF-α, and IL-1ß Concentrations in Women Undergoing Surgery for Breast Cancer.

BACKGROUND: Vascular endothelial growth factor-C (VEGF-C), tumor necrosis factor-α (TNF-α), and interleukin-1ß(IL-1ß) have been shown to be associated with the recurrence and metastasis of breast cancer after surgery. This study tested the hypothesis that patients undergoing surgery for breast cancer, who received postoperative analgesia with flurbiprofen axetil combined with small doses of fentanyl (FA), exhibited reduced levels of VEGF-C, TNF-α, and IL-1ß compared with those patients receiving fentanyl alone (F). METHOD: Forty-women with primary breast cancer undergoing a modified radical mastectomy were randomized to receive postoperative analgesia with flurbiprofen axetil combined with fentanyl or fentanyl alone. Venous blood was sampled before anesthesia, at the end of surgery, and at 48 hours after surgery, and the serum was analyzed. The primary endpoint was changes in the VEGF-C concentrations in serum. RESULTS: Group FA patients reported similar analgesic effects as group F patients at 2, 24, and 48 hours. At 48 hours, mean postoperative concentrations of VEGF-C in group F patients were higher than in group FA patients, 730.9 versus. 354.1 pg/mL (P = 0.003), respectively. The mean postoperative concentrations of TNF-α in group F patients were also higher compared with group FA patients 27.1 vs. 15.8 pg/mL (P = 0.005). Finally, the mean postoperative concentrations of IL-1ß in group F were also significantly higher than in group FA 497.5 vs. 197.7 pg/mL (P = 0.001). CONCLUSION: In patients undergoing a mastectomy, postoperative analgesia with flurbiprofen axetil, combined with fentanyl, were associated with decreases in serum concentrations of VEGF-C, TNF-α, and IL-1ß compared with patients receiving doses of only fentanyl.

Aggregation-Induced Structural Symmetry Breaking Promotes Charge Separation for Efficient Photocatalytic Hydrogen Production.

Recently, organic semiconductors have received much attention in the field of photocatalysis due to their tunable physicochemical properties. However, organic semiconductor photocatalysts typically suffer from severe charge recombination due to high exciton binding energy. Herein, we found that aggregation of pyrene results in a red-shift of the light absorption from UV to visible light region. Importantly, the aggregation can induce dipole polarization by spontaneous structural symmetry breaking, thus significantly accelerating the separation and transfer of charge carriers. As a result, the pyrene aggregates display enhanced hydrogen photosynthesis activity. Furthermore, the noncovalent interactions allow rational design of physicochemical and electronic properties of pyrene aggregates, further strengthening the charge separation and photocatalytic activity of aggregates. The quantum yield of pyrene aggregates for hydrogen production highly reaches 20.77 % at 400 nm. Moreover, we have also observed pyrene analogues (1-hydroxypyrene, 1-nitropyrene and perylene) after aggregation all display large dipole moments induced by structural symmetry breaking and therefore accelerate the separation of charge carriers, confirming its general principle. This work highlights the achievement of using aggregation-induced structural symmetry breaking to enable the separation and transfer of charge carriers.

Prognostic and risk factor analysis of cancer patients after unplanned ICU admission: a real-world multicenter study.

To investigate the occurrence and 90-day mortality of cancer patients following unplanned admission to the intensive care unit (ICU), as well as to develop a risk prediction model for their 90-day prognosis. We prospectively analyzed data from cancer patients who were admitted to the ICU without prior planning within the past 7 days, specifically between May 12, 2021, and July 12, 2021. The patients were grouped based on their 90-day survival status, and the aim was to identify the risk factors influencing their survival status. A total of 1488 cases were included in the study, with an average age of 63.2 ± 12.4 years. The most common reason for ICU admission was sepsis (n = 940, 63.2%). During their ICU stay, 29.7% of patients required vasoactive drug support (n = 442), 39.8% needed invasive mechanical ventilation support (n = 592), and 82 patients (5.5%) received renal replacement therapy. We conducted a multivariate COX proportional hazards model analysis, which revealed that BMI and a history of hypertension were protective factors. On the other hand, antitumor treatment within the 3 months prior to admission, transfer from the emergency department, general ward, or external hospital, high APACHE score, diagnosis of shock and respiratory failure, receiving invasive ventilation, and experiencing acute kidney injury (AKI) were identified as risk factors for poor prognosis within 90 days after ICU admission. The average length of stay in the ICU was 4 days, while the hospital stay duration was 18 days. A total of 415 patients died within 90 days after ICU admission, resulting in a mortality rate of 27.9%. We selected 8 indicators to construct the predictive model, which demonstrated good discrimination and calibration. The prognosis of cancer patients who are unplanned transferred to the ICU is generally poor. Assessing the risk factors and developing a risk prediction model for these patients can play a significant role in evaluating their prognosis.

[Effect of intrathecal sufentanil and protein kinase C inhibitor on pain threshold and the expression of NMDA receptor/ CGRP in spinal dorsal horn in rats with neuropathic pain].

OBJECTIVE: To investigate the effect of intrathecal sufentanil and protein kinase C inhibitor on pain threshold and the expression of N-methyl-D-aspartate receaptors (NMDAR)/calcitonin generelated peptide (CGRP) in spinal dorsal horn in rats with neuropathic pain. METHODS: Fifty-four healthy male Sprague-Dawley rats were randomly divided into 6 groups (9 in each group). The rats in the sham group(Group S) + spared nerve injury (SNI), SP+SNI, and P+SNI were intrathecally injected sufentanil (1 µg), sufentanil (1 µg) and chelerythrine chloride (11 µg), chelerythrine chloride (11 µg) followed by 10 µL normal saline once every day for 14 days postoperatively, respectively. Similarly, rats in the control group (Group C), the sham group (Group S), and SNI model group (Group SNI) were intrathecally injected 20 µL normal saline in the uniform interval. Pain behaviours were measured on Day 1 pre-surgery and on Day 1, 2, 7, and 14 after the intrathecal injection. The expressions of NMDAR and CGRP in the spinal dorsal horn of L5 segment were determined by immunohistochemistry on Day 2, 7, and 14 after the intrathecal injection. RESULTS: Compared with Group C and Group S, mechanical allodynia threshold in group SNI was decreased after the surgery (P<0.01), and expressions of NMDAR and CGRP immunoreactive soma in the spinal dorsal horn was significantly increased (P<0.01). Mechanical stimulation pain threshold was elevated in Group S+SNI, Group P+SNI, and Group SP+SNI compared with Group SNI (P<0.01), while expressions of NMDAR and CGRP immunoreactive soma in Group S+SNI, Group P +SNI, and Group SP+SNI were significantly decreased (P<0.05 or 0.01). CONCLUSION: Intrathecal administration of sulfentanil and protein kinase C inhibitor can provide significant antinociception in rats with neuropathic pain and obviously inhibit the upregulation of NMDAR and CGRP expressions in the spinal dorsal horn of SNI rat models.

Strong coordination ability of sulfur with cobalt for facilitating scale-up synthesis of Co9S8 encapsulated S, N co-doped carbon as a trifunctional electrocatalyst for oxygen reduction reaction, oxygen and hydrogen evolution reaction.

High activity trifunctional non-noble electrocatalysts, targeting oxygen reduction reaction (ORR), hydrogen evolution reaction (HER), and oxygen evolution reaction (OER), are rationally designed by integrating the merits of both Co9S8 nanoparticles and carbons nanosheets. Herein, Co9S8 loaded with S, N co-doped carbon core-shell catalyst (Co9S8@SNC) was reasonably designed and synthesized by using the strong coordination effect between Co2+ and CS at the molecular level. The significant synergistic effect between the S, N co-doped carbon shell and Co9S8 core endows the catalyst with excellent catalytic performance for ORR, HER, and OER reactions. The carbon shell enhances the conductivity of the hybrid material, while the Co9S8 core provides the main catalytic active sites. More specifically, the half-wave potential for ORR is 0.846 mV, and the overpotential at 10 mA cm-2 for OER and HER are 320 mV and 170 mV, respectively. To test its practical application, zinc-air battery assembled by Co9S8@SNC shows a high power density of 239 mW cm-2, excellent rechargeability, and long cyclic stability. This work provides a promising and extensible method to in-situ synthesize core-shell metal sulfides loaded S, N co-doped carbon composites, which can be a promising candidate for electrocatalytic material in energy storage and conversion devices.

Modification of C.I. Pigment Red 146 with surfactants and graphene oxide.

Organic pigments are important in a range of fields, from printing ink to industrial coatings. Azo pigments are some of the most common pigments in use today, but they typically have poor solvent solubility and tend to agglomerate. Consequently, the size and crystal structure of the pigment particles has a crucial effect on their optical and physical properties, such as color strength and solvent resistance, respectively. Several technologies, such as microreactors, have been developed to control pigment particle size, but an in-depth study of the effects of modification conditions on pigment properties (color, flowability, and solvent resistance) has not been reported to date. Therefore, in this paper, we report the surface modification of C.I. Pigment Red 146 particles using anionic (Igepon T) and non-ionic surfactants (Peregal O-25) and additives (DB-60 as the second diazo component and graphene oxide) on the pigment properties. In addition, we examined the effect of hydrothermal treatment at different temperatures on the same properties. The various modifications resulted in an increase in the solvent resistance, a reduction in the particle size (from 30.581 to 12.252 µm), a narrowing of the particle size distribution, and an increase in hydrophilicity. In addition, the color brightness and brilliance were significantly improved, and the maximum color strength reached 112.6%. These findings have applications for the development of pigments having enhanced color properties, solvent resistance, and processability.

Light-Induced Synthesis of Oxygen-Vacancy-Functionalized Ni(OH)2 Nanosheets for Highly Selective CO2 Reduction.

Solar-driven CO2 reduction into fuels and chemicals has gained increasing attention in recent years. In this study, oxygen-vacancies-functionalized Ni(OH)2 (OVs-Ni(OH)2 ) nanosheets are synthesized by a photochemical method to serve as a catalyst for CO2 reduction. Characterization reveals that COOH* is the key intermediate for CO2 -to-CO photoreduction. Experimental results and theoretical calculations confirm that OVs modification can greatly modulate the interaction strength between the OVs-Ni(OH)2 and CO2 , while lowering the energy barrier for COOH* formation, thereby preferentially facilitating CO2 reduction. As a result, the OVs-Ni(OH)2 catalyst exhibits outstanding activity and selectivity for CO2 -to-CO photoreduction with visible light. A CO evolution rate of 31.58 µmol h-1 (0.35 mg catalyst, 90228 µmol h-1 g-1 ) with a selectivity of 98 % over OVs-Ni(OH)2 was achieved, outperforming most analogous reported catalysts. Moreover, even under a low CO2 concentration of 0.04 % (representative of the CO2 concentration in air) and low reaction temperature (273 K, 0 °C), this catalyst can still trigger CO2 reduction. This work provides a new method to synthesize OVs-Ni(OH)2 catalysts for efficient CO2 reduction and establishes a relationship between the OVs and the catalytic activity, which may guide the design of highly selective CO2 reduction catalysts.

A semi-crystalline carbonaceous structure as a wide-spectrum-responsive photocatalyst for efficient redox catalysis.

Herein, we synthesized an oxygen- and nitrogen-containing carbonaceous structure (ONCS). This ONCS possessed exceptional light-harvesting ranging from the visible to NIR light region. Characterization results confirmed that the ONCS was an n-type semiconductor. The ONCS can efficiently catalyze hydrogen photosynthesis and benzyl alcohol oxidation under visible light, even under NIR light irradiation.

Combined use of gap-PCR and next-generation sequencing improves thalassaemia carrier screening among premarital adults in China.

AIMS: Thalassaemia is one of the most common genetics disorders in the world, especially in southern China. The aim of the present study was to investigate the feasibility of combining the gap-PCR and next-generation sequencing (NGS) for thalassaemia carrier screening in the Chinese population. METHODS: Blood samples were obtained from 944 prepregnancy couples; thalassaemia carrier screening was performed by using a routine haematological method and a combination of gap-PCR and NGS method. RESULTS: We found that the α thalassaemia carrier rate was 11% (207/1888); the ß thalassaemia carrier rate was 3.7% (70/1888); the composite α thalassaemia and ß thalassaemia carrier rate was 0.4% (8/1888). We also identified seven novel mutations, including HBA1: c.412A>G, -50 (G>A), HBB: c.*+129T>A, HBB: c.-64G>C, HBB: c.-180G>C, HBB: c.*+5G>A and HBB: c.-113A>G. By comparing the combined gap-PCR and NGS method, the MCV+MCH and HbA2 detection strategy showed a lower sensitivity of 61.05% (105/172) and a higher missed diagnosis ratio of 38.95% (67/172) for α thalassaemia mutations. The sensitivity was improved with the MCV+MCH and HbA2 detection screen when compared with MCV+MCH detection for ß thalassaemia (98.51% vs 85.90%). CONCLUSIONS: Our study suggests the combined gap-PCR and NGS method is a cost-effective method for the thalassaemia carrier screening, particularly for the α thalassaemia mutation carriers.

Facile synthesis of hierarchical mesopore-rich activated carbon with excellent capacitive performance.

Mesoporous carbons attract increasing attention owing to their potential applications in supercapacitors. So far, controlled synthesis of mesoporous carbons with a narrow pore size distribution relies largely on the complicated template methods. To avoid the use of templates, a surfactant-free emulsion polymerization method is presented for the fabrication of a melamine-modified phenolic resin microrod (MPRR) assembled by micron-sized spherical cells and thin walls. In addition, one-step KOH activation strategy is adopted to synthesize hierarchical mesoporous activated carbon with 2-10 nm narrow mesopores by using MPRR as carbon precursors. The as-prepared mesoporous activated carbon has a high specific surface area of about 2758 m2 g-1 and a mesopore volume of 0.54 cm3 g-1 (calculated by density functional theory), comprising ∼43.5% of total pore volume (∼1.43 cm3 g-1). Hierarchical mesopores can significantly accelerate ion transfer and increase micropore accessibility, which endow the carbon with high specific capacitance equal to 409 F g-1 at 0.1 A g-1 and 268 F g-1 at 100 A g-1 in 6 M KOH electrolyte, with a high capacitance retention of 66%. Moreover, the assembled symmetric supercapacitor also exhibits good cycling stability in KOH electrolyte and delivers high power density equal to 12080 W kg-1 when energy density is 5.02 Wh kg-1. This finding provides an insight into directional tailoring of mesoporous structures of phenolic resin-based carbon materials at the molecular level for high-performance supercapacitors.

Oxygen-rich hierarchically porous carbons derived from pitch-based oxidized spheres for boosting the supercapacitive performance.

Oxygen-rich hierarchically porous carbons are prepared by employing one-step KOH activation of pitch-based oxidized spheres (POS) as carbon precursors. The activation temperatures not only allow directed tailoring the porosity of carbon but also guarantee the preservation of moderate oxygen functional groups from POS, which are beneficial for efficiently integrating the electrical double layer capacitance and pseudocapacitance in one electrode. The as-prepared pitch-based activated carbons (PAC) possesses a high specific surface area of 2245 m2 g-1 with well-developed micropores, appropriate meso-macropores, and rich oxygen doping of 15.9 at%. Benefiting from the synergistic effect of hierarchical porosity and pseudocapacitive oxygen groups, PAC exhibit high specific capacitance of 427F g-1 and 302F g-1 at 0.5 A g-1 and 50 A g-1, respectively, as well as excellent capacitance retention of 71% in a three-electrode system with 6 M KOH electrolyte. Moreover, the as-assembled symmetrical supercapacitor displays a high energy of 5.79 Wh kg-1 at a power density of 9918 W kg-1 with excellent cycling stability with capacitance retention of 95% at 5 A g-1 after 10,000 cycles, which is higher than that of commercial Kuraray YP-50F. This finding demonstrates that one-step KOH activation coupled with oxygen-rich pitch may act as an optimal component to finely tailor the porosity and oxygen doping on activated carbons for energy storage applications.

Synergistic Effect of Oxygen Vacancies and Ni Species on Tuning Selectivity of Ni/ZrO2 Catalyst for Hydrogenation of Maleic Anhydride into Succinic Anhydride and γ-Butyrolacetone.

ZrO2 nanoparticles, ZrO2 (P) and ZrO2 (H), with different tetragonal phase contents, were prepared. ZrO2 (P) possessed higher tetragonal phase content than ZrO2 (H). Ni/ZrO2 catalysts (10% (w/w)), using ZrO2 (P) and ZrO2 (H) as supports, were prepared using an impregnation method, and were characterized using XRD, Raman, H2-TPR, XPS, and H2-TPD techniques. Their catalytic performance in maleic anhydride hydrogenation was tested. The Ni/ZrO2 (P) catalyst exhibited stronger metal-support interactions than the Ni/ZrO2 (H) catalyst because of its higher number of oxygen vacancies and the low-coordinated oxygen ions on its surface. Consequently, smaller Ni crystallites and a higher C=C hydrogenation activity for maleic anhydride to succinic anhydride were obtained over a Ni/ZrO2 (P) catalyst. However, the C=O hydrogenation activity of Ni/ZrO2 (P) catalyst was much lower than that of the Ni/ZrO2 (H) catalyst. A 43.5% yield of γ-butyrolacetone was obtained over the Ni/ZrO2 (H) catalyst at 210 °C and 5 MPa of H2 pressure, while the yield of γ-butyrolactone was only 2.8% over the Ni/ZrO2 (P) catalyst under the same reaction conditions. In situ FT-IR characterization demonstrated that the high C=O hydrogenation activity for the Ni/ZrO2 (H) catalyst could be attributed to the surface synergy between active metallic nickel species and relatively electron-deficient oxygen vacancies.

Rational Surface Tailoring Oxygen Functional Groups on Carbon Spheres for Capacitive Mechanistic Study.

Porous carbons represent a typical class of electrode materials for electric double-layer capacitors. However, less attention has been focused on the study of the capacitive mechanism of electrochemically active surface oxygen groups rooted in porous carbons. Herein, the degree and variety of oxygen surface groups of HNO3-modified samples (N-CS) are finely tailored by a mild hydrothermal oxidation (0.0-3.0 mol L-1), while the micro-meso-macroporous structures are efficiently preserved from the original sample. Thus, N-CS is a suitable carrier for separately discussing the contribution of oxygen functional groups to the electrochemical property. The optimized N-CS shows a high capacitance of 279.4 F g-1 at 1 A g-1, exceeding 52.8% of pristine carbon sphere (CS) (182.8 F g-1 at 1 A g-1) in KOH electrolyte. On further deconvoluting the redox peaks of cyclic voltammetry curves, we find that the pseudocapacitance not only associates with the surface-controlled faradic reaction at high scan rate but also dramatically stems from the diffusion-controlled capacitance through potassium and hydroxyl ion insertion/deinsertion into the underutilized micropores at low scan rate. The assembled supercapacitor based on N-CS presents a stable energy density of 5 Wh kg-1 over a wide range of power density of 250-5000 W kg-1, which is higher than 0.0N-CS in KOH electrolyte. In TEABF4 electrolyte, the N-CS supercapacitor has an energy density of 26.9 Wh kg-1 at the power density of 1350 W kg-1 and exhibits excellent cycling stability with a capacitance retention of 93.2% at 2 A g-1 after 10 000 cycles. These results demonstrate that surface oxygen groups alter the capacitive mechanism and contribution of porous carbons.

Nitrogen and sulfur Co-doped microporous activated carbon macro-spheres for CO2 capture.

Millimeter-sized nitrogen and sulfur co-doped microporous activated carbon spheres (NSCSs) were first synthesized from poly(styrene-vinylimidazole-divinylbenzene) resin spheres through concentrated H2SO4 sulfonation, carbonization and KOH activation. Styrene (ST) and N-vinylimidazole (VIM) were carbon and nitrogen sources, while the sulfonic acid functional groups introduced by the simple concentrated sulfuric acid sulfonation worked simultaneously as cross-linking agent and sulfur source during the following thermal treatments. It was found that the surface chemistries, textural structures, and CO2 adsorption performances of the NSCSs were significantly affected by the addition of VIM. The NSCS-4-700 sample with a molar ratio of ST: VIM = 1: 0.75 showed the best CO2 uptake at different temperatures and pressures. An exhaustive adsorption evaluation indicated that CO2 sorption at low pressures originated from the synergistic effect of surface chemistry and micropores below 8.04 Å, while at the moderate pressure of 8.0 bar, CO2 uptake was dominated by the volume of micropores. The thermodynamics suggested the exothermic and orderly nature of the adsorption process, which was dominated by a physisorption mechanism. The high CO2 adsorption capacity, fast kinetic adsorption rate, and great regeneration stability of the nitrogen and sulfur co-doped activated carbon spheres indicated that the as-prepared carbon adsorbents were good candidates for large-scale CO2 capture.

Discovery of 4-aryl-4H-chromenes as a new series of apoptosis inducers using a cell- and caspase-based high-throughput screening assay. 3. Structure-activity relationships of fused rings at the 7,8-positions.

As a continuation of our efforts to discover and develop the apoptosis-inducing 4-aryl-4H-chromenes as novel anticancer agents, we explored the SAR of fused rings at the 7,8-positions. It was found that a five-member aromatic ring, such as pyrrolo with nitrogen at either the 7- or 9-position, is preferred. A six-member aromatic ring, such as benzo or pyrido, also led to potent compounds. The SAR of the 4-aryl group was found to be similar for chromenes with a fused ring at the 7,8-positions. These compounds were found to inhibit tubulin polymerization, indicating that cyclization of the 7,8-positions into a ring does not change the mechanism of action. Compound 2h was identified to be a highly potent apoptosis inducer with an EC50 of 5 nM and a highly potent inhibitor of cell proliferation with a GI50 of 8 nM in T47D cells.

Ammonia-induced robust photocatalytic hydrogen evolution of graphitic carbon nitride.

We report a new and effective method to prepare high activity graphitic carbon nitride (g-C3N4) by a simple ammonia etching treatment. The obtained g-C3N4 displays a high BET surface area and enhanced electron/hole separation efficiency. The hydrogen evolution rates improved from 52 µmol h(-1) to 316.7 µmol h(-1) under visible light.

Discovery of 4-aryl-4H-chromenes as a new series of apoptosis inducers using a cell- and caspase-based high-throughput screening assay. 1. Structure-activity relationships of the 4-aryl group.

By applying a novel cell- and caspase-based HTS assay, 2-amino-3-cyano-7-(dimethylamino)-4-(3-methoxy-4,5-methylenedioxyphenyl)-4H-chromene (1a) has been identified as a potent apoptosis inducer. Compound 1a was found to induce nuclear fragmentation and PARP cleavage, as well as to arrest cells at the G(2)/M stage and to induce apoptosis as determined by the flow cytometry analysis assay in multiple human cell lines (e.g. Jurkat, T47D). Through structure-activity relationship (SAR) studies of the 4-aryl group, a 4- and 7-fold increase in potency was obtained from the screening hit 1a to the lead compounds 2-amino-4-(3-bromo-4,5-dimethoxyphenyl)-3-cyano-7-(dimethylamino)-4H-chromene (1c) and 2-amino-3-cyano-7-(dimethylamino)-4-(5-methyl-3-pyridyl)-4H-chromene (4e), with an EC(50) of 19 and 11 nM in the caspase activation assay in T47D breast cancer cells, respectively. The 2-amino-4-aryl-3-cyano-7-(dimethylamino)-4H-chromenes also were found to be highly active in the growth inhibition MTT assay, with GI(50) values in the low nanomolar range for compound 1c. Significantly, compound 1c was found to have a GI(50) value of 2 nM in the paclitaxel resistant, p-glycoprotein overexpressed, MES-SA/DX5 tumor cells. Functionally, compound 1c was found to be a potent inhibitor of tubulin polymerization and to effectively inhibit the binding of colchicine to tubulin. These results confirm that the cell-based caspase activation assay is a powerful tool for the discovery of potent apoptosis inducers and suggest that the 4-aryl-4H-chromenes have the potential to be developed into future anticancer agents.