Herein, the electrodeposited-film electrode CFeCoNiP was fabricated to serve as a bifunctional electrocatalyst for the hydrogen evolution reaction (HER) and oxygen evolution reaction (OER). Kinetic ...Tafel slope analysis suggests that the HER follows the Volmer-Tafel mechanism (29 mV dec
−1
), indicating that the recombination of the two adsorbed hydrogen atoms is the rate-determining step. The FeCoNi-based thick film (thickness: 168.3 μm) shows a metallic state favorable for electron transfer; on the other hand, in the case of the FeCoNi-based thin film (thickness: 389.2 nm), the in
operando
XAS investigation reveals that Fe
3+
-assisted water dissociation promotes the formation of Co
2+
-μ-H-Ni
3+
(catalyst-H
ad
) species, which subsequently undergoes reductive elimination to furnish H
2
gas
via
the HER process. During the OER, the CoNi-oxide matrix acts as a chemical and electroconductive host to build/stabilize the key intermediate Fe
4+
&z.dbd;O/Fe
3+
-O&z.rad; motifs; this subsequently triggers the catalytic O-O bond formation (30 mV dec
−1
) through the radical-radical coupling of the adjacent Fe
4+
&z.dbd;O/Fe
3+
-O&z.rad; motifs or/and OH
−
attack on the Fe
4+
-induced electrophilic oxygen center, leading to the release of O
2
. The mechanistic experiments provide advanced insights into the catalytic kinetics/intermediates and demonstrate that the electronically cooperative interplay among Fe/Co/Ni leads to enhanced alkaline water electrolysis. The CFeCoNiP catalyst exhibits an excellent HER activity (specific activity
j
s
= 0.227 mA cm
−2
) with a low charge transfer resistance (3.9 Ω) and an overpotential of 37 mV, achieving the current density of 10 mA cm
2
; moreover, it shows good OER activity (
j
s
= 1.798 mA cm
−2
) with low charge transfer resistance (2.1 Ω) and an overpotential of 250 mV, approaching a current density of 10 mA cm
−2
in a 1 M NaOH aqueous solution. The CFeCoNiP/NF (electrodeposited on Ni foam) electrode-pair device achieved the current densities of 100 and 500 mA cm
−2
at the voltages of 1.65 and 1.86 V, respectively, under alkaline conditions.
In operando XAS investigation on FeCoNi-based thin film unravels that Fe
3+
-assisted water dissociation promotes the formation of Co
2+
-μ-H-Ni
3+
species, and the conductive character of Co
2+
Ni
3+
-oxide matrix facilitates the coupling of adjacent Fe
4+
&z.dbd;O/Fe
3+
-O&z.rad; motifs.
Common CO2-based polycarbonates are known to be highly hydrophobic, and this “inert” property makes them difficult for the covalent immobilization of bioactive molecules. A practical method for ...modifying polymers is to introduce various functional groups that permit decoration of polymer chains with bioactive substances. In this report, CO2-based poly(2-vinyloxirane carbonate) (PVIC) with more than 99% carbonate linkages is isolated from the CO2/2-vinyloxirane alternating copolymerization catalyzed by the bifunctional catalyst (1R,2R)-SalenCo(III)(DNP)2 (1) (DNP = 2,4-dinitrophenolate) bearing a quaternary ammonium salt on the ligand framework. It was also observed that the presence of propylene oxide significantly activates 2-vinyloxirane for incorporation into the polymer chain as well as inhibits the formation of cyclic carbonate in the terpolymerization process. DSC studies demonstrate that the glass transition temperature (T g) decreases with the increase in the content of vinyl groups in the polycarbonate. By way of thiol–ene coupling, showing mainly “click” characteristics and nearly quantitative yields, amphiphilic polycarbonates (PVIC-OH and PVIC-COOH) with multiple hydroxy or carboxy functionalities have been prepared, providing suitable reactivities for further modifications (ring-opening of l-aspartic acid anhydride hydrochloride salt and deprotonation by aqueous ammonium hydroxide (NH4OH(aq))) to successfully isolate the water-soluble CO2-based polycarbonate PVIC-COONH4, and the PVIC-OH-Asp polymer which shows particles dispersed in water with an average hydrodynamic diameter D n = 32.2 ± 8.8 nm. It is presumed that this emerging class of amphiphilic/water-soluble polycarbonates could embody a powerful platform for bioconjugation and drug conjugation. In contrast to lower T gs of PVIC, (PVIC-co-PC), PVIC-OH, and PVIC-COOH, the polycarbonates PVIC-OH-Asp and PVIC-COONH4 show higher T gs as a consequence of their intrinsic ionic property (ammonium salts).
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IJS, KILJ, NUK, PNG, UL, UM
To investigate synergistic effect between geometric and electronic structures on directing CO2RR selectivity, water phase synthetic protocol and surface architecture engineering strategy are ...developed to construct monodispersed Bi‐doped Cu‐based nanocatalysts. The strongly correlated catalytic directionality and Bi3+ dopant can be rationalized by the regulation of *COOH/*CO adsorption capacities through the appropriate doping of Bi3+ electronic modulator, resulting in volcano relationship between FECO/TOFCO and surface EVBM values. Spectroscopic study reveals that the dual‐site binding mode (Cu─μ─C(═O)O─Bi3+) enabled by Cu1Bi3+2 motif in single‐phase Cu150Bi1 nanocatalyst drives CO2‐to‐CO conversion. In contrast, the study of dynamic Bi speciation and phase transformation in dual‐phase Cu50Bi1 nanocatalyst unveils that the Bi0‐Bi0 contribution emerges at the expense of BOC phase, suggesting metallic Bi0 phase acting as H˙ formation center switches CO2RR selectivity toward CO2‐to‐HCOO− conversion via *OCHO and *OCHOK intermediates. This work provides significant insight into how geometric architecture cooperates with electronic effect and catalytic motif/phase to guide the selectivity of electrocatalytic CO2 reduction through the distinct surface‐bound intermediates and presents molecular‐level understanding of catalytic mechanism for CO/HCOO− formation.
This work provides significant insight into how geometric architecture (single‐phase vs dual‐phase) cooperates with electronic effect (surface d‐band center modulation by Bi3+ dopant) and catalytic motif/phase (Cu1Bi3+2 vs Bi0) to guide the selectivity of CO2 electro‐reduction through the distinct surface‐bound intermediates (CO2˙ˉ vs H˙) for CO/HCOO− formation.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Abstract Chloroquine (CQ) and hydroxychloroquine (HCQ), two antimalarial drugs, are suggested to have potential anticancer properties. in the present study, we investigated the effects of CQ and HCQ ...on cell growth of bladder cancer with emphasis on autophagy inhibition and apoptosis induction in vitro . The results showed that CQ and HCQ inhibited the proliferation of multiple human bladder cell lines (including RT4, 5637, and T24) in a time- and dose-dependent fashion, especially in advanced bladder cancer cell lines (5637 and T24) compared to immortalized uroepithelial cells (SV-Huc-1) or other reference cancer cell lines (PC3 and MCF-7). We found that 24-hour treatment of CQ or HCQ significantly decreased the clonogenic formation in 5637 and T24 cells compared to SV-Huc-1. As human bladder cancer tumor exhibits high basal level of autophagic activities, we detected the autophagic flux in cells treated with CQ and HCQ, showing an alternation in LC3 flux in CQ- or HCQ-treated cells. Moreover, bladder cancer cells treated with CQ and HCQ underwent apoptosis, resulting in increased caspase 3/7 activities, increased level of cleaved poly(ADP-ribose) polymerase (PARP), caspase 3, and DNA fragmentation. Given these results, targeting autophagy with CQ and HCQ represents an effective cancer therapeutic strategy against human bladder cancer.
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FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
A high basal level of autophagic flux in bladder cancer (BC) cells prevents cell death and weakens chemotherapy efficacy. However, how autophagy influences cancer‐associated immunosuppression in BC ...remains undetermined. In this study, we observed a negative correlation between the autophagy‐related markers LC3‐II and programmed death ligand‐1 (PD‐L1) in BC cells. The autophagy inhibitors chloroquine (CQ) and bafilomycin A1 (Baf‐A1) increased PD‐L1 expression in BC cells through the ERK–JNK–c‐Jun signal‐transduction pathway. Moreover, the treatment of BC cells with CQ and Baf‐A1 inhibited hsa‐microRNA‐34a (miR‐34a) expression and miR‐34a overexpression in BC cells prevented the autophagy blockade–induced PD‐L1 expression; a negative correlation between miR‐34a and PD‐L1 expression was observed during treatment with autophagy inhibitors. Furthermore, miR‐34a overexpression induced the cytotoxic activity of natural killer cells against BC cells. Our results provide evidence that autophagy blockade and its regulatory pathway affect cancer‐associated immunosuppression through PD‐L1 elevation. Thus, the coadministration of autophagy inhibitors and a PD‐L1 immune checkpoint blockade provides a potential therapeutic approach for treating BC.
Graphical
Our model illustrates the pharmacological inhibition of autophagy could induce PD‐L1 expression in BC cells through the ERK–JNK–c‐Jun signaling transduction pathway and miR‐34a downregulation, revealing the effect of genetic and epigenetic regulation of autophagy on PD‐L1. In consequence, BC cells expressing PD‐L1 suppress NK cell cytotoxic activity.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Bladder cancer (BC) is the second most common urologic malignancy and the ninth most common malignancy worldwide. Surgical resection is the mainstay of treatment for patients with early-stage ...disease, whereas therapeutic options are limited for patients with advanced-stage or residual BC. Programmed cell death ligand-1 (PD-L1) is an important target for immunotherapy. It is known that PD-L1 is overexpressed in BC; a clinical trial involving PD-L1 immune checkpoint inhibitors in advanced BC is ongoing. In the present study, we used Western blot and quantitative real-time PCR (qPCR) to define the expression level of PD-L1 after cisplatin treatment in BC-derived cell lines. The signal activation was also evaluated by Western blot in BC-derived cell lines. We found that chemotherapeutic drug cisplatin can induce PD-L1 but not PD-L2 expression in BC-derived cell lines. Furthermore, the expression level of PD-L1 was increased in a dose- and time-dependent manner after cisplatin treatment. The cisplatin-induced PD-L1 expression is mainly mediated by ERK1/2 but not Akt/mTOR signal pathway. Moreover, we found that cisplatin activates transcription factor activator protein-1 (AP-1) to regulate PD-L1 expression. The chemotherapy drug such as cisplatin may trigger resistance of BC through PD-L1 up-regulation. The present study suggests that PD-L1 antibody should be used concomitantly with chemotherapy in the setting of advanced and metastatic BC.
Bladder cancer (BC) is the second most common urological tumour in Western countries. Approximately, 80% of patients with BC will present with non-muscle invasive bladder cancer (NMIBC), whereas a ...quarter will have muscle invasive disease (MIBC) at the time of BC diagnosis. However, patients with NMIBC are at risk of BC recurrence or progression into MIBC, and an MIBC prognosis is determined by the presence of progression and metastasis. Matrix metalloproteinase 2 (MMP2), a type of matrix metalloproteinase (MMP), plays a major role in tumour invasion and is well-characterized in BC prognosis. In BC, the mechanisms regulating MMP2 expression, and, in turn, promote cancer invasion, have hardly been explored. Thrombospondin-4 (THBS4/TSP4) is a matricellular glycoprotein that regulates multiple biological functions, including proliferation, angiogenesis, cell adhesion and extracellular matrix modelling. Based on the results of a meta-analysis in the Gene Expression Profiling Interactive Analysis 2 database, we observed that TSP4 expression levels were consistent with overall survival (OS) rate and BC progression, with the highest expression levels observed in the advanced stages of BC and associated with poor OS rate. In our pilot experiments, incubation with recombinant TSP4 promoted the migration and invasion in BC cells. Furthermore, MMP2 expression levels increased after recombinant TSP4 incubation. TSP4-induced-MMP2 expression and cell motility were regulated via the AKT signalling pathway. Our findings facilitate further investigation into TSP4 silencing-based therapeutic strategies for BC.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
By regulating the electronic environment of Fe active centers to modulate electrocatalytic CO
2
reduction behavior, an advanced dual Fe
2
-site catalyst (Fe
2
DAC) exhibiting CO current density (
j
...CO
) of 10 mA cm
−2
at an overpotential of 330 mV in a CO
2
-saturated 0.5 M KHCO
3
electrolyte was designed and characterized by HAADF-STEM microscopy and XAS/EPR spectroscopies. With regard to Fe
2
DAC displaying a higher charge transfer coefficient (
α
= 0.53), turnover frequency (TOF
CO
= 2.03 s
−1
), and CO faradaic efficiency (FE
CO
= 98.6%) at an overpotential of 400 mV compared to that of single iron atom catalyst (Fe SAC,
α
= 0.31, TOF
CO
= 0.25 s
−1
, FE
CO
= 60.1%), the kinetic mechanism was investigated/elucidated by the cation effect and
in operando
spectroscopy. The higher DMPO-CO
2
EPR intensity (
g
= 2.0065,
a
N
= 15.6 G,
a
H
= 18.9 G) and the smaller separation of ATR-SEIRAS stretching frequencies (1554 (
ν
asym
), 1288 (
ν
sym
) cm
−1
, Δ
ν
= 266 cm
−1
) suggest that the structural type of the *COOCs&z.rad;/*COOCs
−
intermediate is μ
2
-η3 CO
2
coordination (class II) for Fe
2
DAC-triggered electrocatalytic CO
2
reduction in CO
2
-saturated CsHCO
3
solution. The strong orbital interaction among the dual Fe
2
site, intermediate CO
2
&z.rad;
−
/CO
2
2−
, and Cs
+
cation (6s orbital) is proposed to accelerate charge transfer kinetics and shift the rate-determining step from the electron transfer step (Li
+
, Na
+
) to the protonation step (K
+
, Cs
+
), as evidenced by Cs
+
-induced increase in the proton reaction order (0.86) and Cs
+
-induced decrease in the kinetic Tafel slope (57.2 mV dec
−1
) and electrochemical activation energy (23.7 kJ mol
−1
). In contrast, the structural transformation from the dual Fe
II
2
motif to a single Fe
II
site revealed by the disappearance of the Fe-Fe distance (3.10 Å) in
operando
Fe K edge EXAFS lends support to the absence of stretching frequencies (1429 (
ν
asym
), 1380 (
ν
asym
), 1241 (
ν
asym
) cm
−1
) ascribed to μ
2
-η
2
CO
2
coordination in a CO
2
-saturated LiHCO
3
aqueous medium, demonstrating that the transformation of *COOCs
−
/*COOK
−
into the bridge CO
2
2−
Fe-μ-C(&z.dbd;O)O-Fe is vital for electrocatalytic CO
2
-to-CO conversion. In addition to identifying the dinuclear Fe
2
II
site as a catalytic center, this study demonstrates that the thermodynamic stabilization effect of both the cation size (large s orbital/soft hydration shell) and dual Fe
2
II
motif toward CO
2
&z.rad;
−
/CO
2
2−
intermediate is pivotal to the superior CO
2
RR kinetics (activity/selectivity). The proposed pathways (Cs
+
/K
+
/Na
+
vs.
Li
+
and dual Fe
2
site
vs.
single Fe site) may provide insights into how the orbital interaction and the peculiar electronic structure of the dinuclear Fe
2
site impacts the molecular-level mechanism for efficient electrocatalytic CO
2
reduction.
An advanced dual Fe
2
-site catalyst (Fe
2
DAC) exhibiting CO current density (
j
CO
) of 10 mA cm
−2
at an overpotential of 330 mV in a CO
2
-saturated 0.5 M KHCO
3
electrolyte was designed and characterized by HAADF-STEM microscopy and XAS/EPR spectroscopies.
Cisplatin-based chemotherapy is the first line treatment for several cancers including bladder cancer (BC). Autophagy induction has been implied to contribute to cisplatin resistance in ovarian ...cancer; and a high basal level of autophagy has been demonstrated in human bladder tumors. Therefore, it is reasonable to speculate that autophagy may account for the failure of cisplatin single treatment in BC. This study investigated whether cisplatin induces autophagy and the mechanism involved using human BC cell lines.
Human BC cells (5637 and T24) were used in this study. Cell viability was detected using water soluble tetrazolium-8 reagents. Autophagy induction was detected by monitoring the levels of light chain 3 (LC3)-II and p62 by Western blot, LC3-positive puncta formation by immunofluorescence, and direct observation of the autophagolysosome (AL) formation by transmission electron microscopy. Inhibitors including bafilomycin A1 (Baf A1), chloroquine (CQ), and shRNA-based lentivirus against autophagy-related genes (ATG7 and ATG12) were utilized. Apoptosis level was detected by caspase 3/7 activity and DNA fragmentation.
Cisplatin decreased cell viability and induced apoptosis of 5637 and T24 cells in a dose-and time-dependent manner. The increased LC3-II accumulation, p62 clearance, the number of LC3-positive puncta, and ALs in cisplatin-treated cells suggested that cisplatin indeed induces autophagy. Inhibition of cisplatin-induced autophagy using Baf A1, CQ, or ATG7/ATG12 shRNAs significantly enhanced cytotoxicity of cisplatin toward BC cells. These results indicated that cisplatin induced protective autophagy which may contribute to the development of cisplatin resistance and resulted in treatment failure. Mechanistically, upregulation of beclin-1 (BECN1) was detected in cisplatin-treated cells, and knockdown of BECN1 using shRNA attenuated cisplatin-induced autophagy and subsequently enhanced cisplatin-induced apoptosis.
Collectively, the study results indicated that cisplatin-induced autophagy is mediated by BECN1 in BC cells. Therefore, combinative treatment using cisplatin and autophagy inhibitors could potentially overcome cisplatin resistance related to autophagy induction.
Bladder cancer (BC), one of the most common urological neoplastic disorders in men, has an extremely low survival rate because of its tendency to metastasize. The anticancer drugs chloroquine (CQ) ...and hydroxy CQ (HCQ) might inhibit tumor progression and invasiveness. However, the mechanism by which CQ and HCQ influence BC is undetermined. In this study, CQ and HCQ treatments inhibited the migration and invasion of two BC cell types (5637 and T24) through expression modulation of matrix metalloproteinase‐2 (MMP‐2), which belongs to the matrix MMP family and is a key mediator of cancer progression. Moreover, additional data revealed that the migrative and invasive effects of BC cells treated with CQ or HCQ were abolished after treatment with rapamycin, which induces autophagy, demonstrating that CQ and HCQ functions in BC are based on autophagy inhibition. In conclusion, our research demonstrated that CQ and HCQ regulated cell motility in BC through MMP‐2 downregulation by targeting autophagy functions, providing a novel therapeutic strategy for BC treatment.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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