Preparation of a Nanosheeted Uranyl-Organic Framework for Enhanced Photocatalytic Oxidation of Toluene.

Preparation of ultrathin metal-organic framework (MOF) nanosheets is an effective way to improve the catalytic efficiency of MOF photocatalysts owing to their superiority in reducing the recombination rate of photogenerated electrons and holes and enhancing charge transfer. Herein, a light-sensitive two-dimensional uranyl-organic framework named HNU-68 was synthesized. Due to its interlayer stacking structure, the corresponding ultrathin nanosheets with a thickness of 4.4 nm (HNU-68-N) can be obtained through ultrasonic exfoliation. HNU-68-N exhibited an enhanced ability to selectively oxidize toluene to benzaldehyde, with the value of turnover frequency being approximately three times higher than that of the bulk HNU-68. This enhancement is attributed to the smaller size and interface resistance of the layered HNU-68-N nanosheets, which facilitate more thorough substrate contact and faster charge transfer, leading to an improvement in the photocatalytic efficiency. This work provides a potential candidate for the application of ultrathin uranyl-based nanosheets.

Light-Initiated Imprinted Membrane-Based Biomimetic SERS Sensor toward Selective Detection of Trace MC-LR.

Microcystin-LR (MC-LR) is a severe threat to human and animal health; thus, monitoring it in the environment is essential, especially in water quality protections. Herein, in this work, we synthesize PVDF/CNT/Ag molecular imprinted membranes (PCA-MIMs) via an innovative combination of surface-enhanced Raman spectroscopy (SERS) detection, membrane separation, and molecular-imprinted technique toward the analysis of MC-LR in water. In particular, a light-initiated imprint is employed to protect the chemical structure of the MC-LR molecules. Furthermore, in order to ensure the detection sensitivity, the SERS substrates are combined with the membrane via the assistance of magnetism. The effect of synthesis conditions on the SERS sensitivity was investigated in detail. It is demonstrated from the characteristic results that the PCA-MIMs present high sensitivity to the MC-LR molecules with excellent selectivity against the interfere molecules. Results clearly show that the as-prepared PCA-MIMs hold great potential applications to detect trace MC-LR for the protection of water quality.

Methoxyhispolon Methyl Ether, a Hispolon Analog, Thwarts the SRC/STAT3/BCL-2 Axis to Provoke Human Triple-Negative Breast Cancer Cell Apoptosis In Vitro.

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer with few treatment options. A promising TNBC treatment approach is targeting the oncogenic signaling pathways pivotal to TNBC initiation and progression. Deregulated activation of signal transducer and activator of transcription 3 (STAT3) is fundamental to driving TNBC malignant transformation, highlighting STAT3 as a promising TNBC therapeutic target. Methoxyhispolon Methyl Ether (MHME) is an analog of Hispolon, an anti-cancer polyphenol found in the medicinal mushroom Phellinus linteus. Still, MHME's anti-cancer effects and mechanisms remain unknown. Herein, we present the first report about MHME's anti-TNBC effect and its action mechanism. We first revealed that MHME is proapoptotic and cytotoxic against human TNBC cell lines HS578T, MDA-MB-231, and MDA-MB-463 and displayed a more potent cytotoxicity than Hispolon's. Mechanistically, MHME suppressed both constitutive and interleukin 6 (IL-6)-induced activation of STAT3 represented by the extent of tyrosine 705-phosphorylated STAT3 (p-STAT3). Notably, MHME-evoked apoptosis and clonogenicity impairment were abrogated in TNBC cells overexpressing a dominant-active mutant of STAT3 (STAT3-C); supporting the blockade of STAT3 activation is an integral mechanism of MHME's cytotoxic action on TNBC cells. Moreover, MHME downregulated BCL-2 in a STAT3-dependent manner, and TNBC cells overexpressing BCL-2 were refractory to MHME-induced apoptosis, indicating that BCL-2 downregulation is responsible for MHME's proapoptotic effect on TNBC cells. Finally, MHME suppressed SRC activation, while v-src overexpression rescued p-STAT3 levels and downregulated apoptosis in MHME-treated TNBC cells. Collectively, we conclude that MHME provokes TNBC cell apoptosis through the blockade of the SRC/STAT3/BCL-2 pro-survival axis. Our findings suggest the potential of applying MHME as a TNBC chemotherapy agent.

Blockade of the SRC/STAT3/BCL-2 Signaling Axis Sustains the Cytotoxicity in Human Colorectal Cancer Cell Lines Induced by Dehydroxyhispolon Methyl Ether.

Colorectal cancer (CRC) is the third most prevalent human cancer globally. 5-Fluorouracil (5-FU)-based systemic chemotherapy is the primary strategy for advanced CRC treatment, yet is limited by poor response rate. Deregulated activation of signal transducer and activator of transcription 3 (STAT3) is fundamental to driving CRC malignant transformation and a poor prognostic marker for CRC, underscoring STAT3 as a promising CRC drug target. Dehydroxyhispolon methyl ether (DHME) is an analog of Hispolon, an anticancer polyphenol abundant in the medicinal mushroom Phellinus linteus. Previously, we have established DHME's cytotoxic effect on human CRC cell lines by eliciting apoptosis through the blockade of WNT/ß-catenin signaling, a preeminent CRC oncogenic pathway. Herein, we unraveled that compared with 5-FU, DHME is a more potent killer of CRC cells while being much less toxic to normal colon epithelial cells. DHME suppressed both constitutive and interleukin 6 (IL-6)-induced STAT3 activation represented by tyrosine 705 phosphorylation of STAT3 (p-STAT3 (Y705)); notably, DHME-induced CRC apoptosis and clonogenicity limitation were abrogated by ectopic expression of STAT3-C, a dominant-active STAT3 mutant. Additionally, we proved that BCL-2 downregulation caused by DHME-mediated STAT3 blockage is responsible for DHME-induced CRC cell apoptosis. Lastly, DHME inhibited SRC activation, and v-src overexpression restored p-STAT3 (Y705) levels along with lowering the levels of apoptosis in DHME-treated CRC cells. We conclude DHME provokes CRC cell apoptosis by blocking the SRC/STAT3/BCL-2 axis besides thwarting WNT/ß-catenin signaling. The notion that DHME targets two fundamental CRC signaling pathways underpins the potential of DHME as a CRC chemotherapy agent.

Sertindole, an Antipsychotic Drug, Curbs the STAT3/BCL-xL Axis to Elicit Human Bladder Cancer Cell Apoptosis In Vitro.

Bladder cancer is the leading urinary tract malignancy. Epidemiological evidence has linked lower cancer incidence in schizophrenia patients to long-term medication, highlighting the anticancer potential of antipsychotics. Sertindole is an atypical antipsychotic agent with reported anticancer action on breast and gastric cancers. Yet, sertindole's effect on bladder cancer remains unaddressed. We herein present the first evidence of sertindole's antiproliferative effect and mechanisms of action on human bladder cancer cells. Sertindole was cytotoxic against bladder cancer cells while less cytotoxic to normal urothelial cells. Apoptosis was a primary cause of sertindole's cytotoxicity, as the pan-caspase inhibitor z-VAD-fmk rescued cells from sertindole-induced killing. Mechanistically, sertindole inhibited the activation of signal transducer and activator of transcription 3 (STAT3), an oncogenic driver of bladder cancer, as sertindole lowered the levels of tyrosine 705-phosphorylated STAT3 along with that of STAT3's target gene BCL-xL. Notably, ectopic expression of the dominant-active STAT3 mutant impaired sertindole-induced apoptosis in addition to restoring BCL-xL expression. Moreover, bladder cancer cells overexpressing BCL-xL were refractory to sertindole's proapoptotic action, arguing that sertindole represses STAT3 to downregulate BCL-xL, culminating in the induction of apoptosis. Overall, the current study indicated sertindole exerts bladder cancer cytotoxicity by provoking apoptosis through targeted inhibition of the antiapoptotic STAT3/BCL-xL signaling axis. These findings implicate the potential to repurpose sertindole as a therapeutic strategy for bladder cancer.

Light-driven uranyl-organic frameworks used as signal-enhanced photoelectrochemical sensors for monitoring anthrax.

The semiconductor-like characteristics and light absorption ability of metal-organic frameworks (MOFs) make it have the potential for photoelectrochemical sensing. Compared with composite and modified materials, the specific recognition of harmful substances directly using MOFs with suitable structures can undoubtedly simplify the fabrication of sensors. Herein, two photosensitive uranyl-organic frameworks (UOFs) named HNU-70 and HNU-71 were synthesized and explored as the novel "turn-on" photoelectrochemical sensors, which can be directly applied to monitor the biomarker of anthrax (dipicolinic acid). Both sensors have good selectivity and stability towards dipicolinic acid with the low detection limits of 1.062 and 1.035 nM, respectively, which are far lower than the human infection concentration. Moreover, they exhibit good applicability in the real physiological environment of human serum, demonstrating a good application prospect. Spectroscopic and electrochemical studies show that the mechanism of photocurrent enhancement results from the interaction between dipicolinic acid and UOFs, which facilitates the photogenerated electron transport.

Protective Effects of Querectin against MPP+-Induced Dopaminergic Neurons Injury via the Nrf2 Signaling Pathway.

BACKGROUND: Parkinson's disease (PD) is a common selective and progressive neurodegenerative disorder of nigrostriatal dopaminergic (DA) neurons. Quercetin is a bioflavonoid with antioxidant, anti-inflammatory, anti-aging and anti-cancer properties. However, the exact mechanism by which quercetin exerts its protective effect on DAergic neurons remains unclear. PURPOSE: To investigate the underlying molecular mechanism of quercetin's protective effect on DA neurons using 1-methyl-4-phenylpyridinium (MPP+)-induced PD ferroptosis model in vitro. METHODS: MPP+ was used to induce cytotoxicity in SH-SY5Y/primary neurons. Cell viability and apoptosis were assessed by CCK-8 assay and flow cytometry. The expression levels of ferroptosis-related proteins (NCOA4, SLC7A11, Nrf2, and GPX4) were determined by Western blotting. Malondialdehyde (MDA), iron, and GPX4 levels were assesed using corresponding assay kits. Lipid peroxidation was assessed by C11-BODIPY staining. RESULTS: In the MPP+-induced ferroptosis model of SH-SY5Y cells, the expressions of SLC7A11 and GPX4 were inhibited, and the expression of NCOA4 protein was increased, causing the overproduction of MDA and lipid peroxidation. Quercetin can reduce the above changes caused by MPP+, that is, reduce the protein expression of NCOA4 in SH-SY5Y cells, increase SLC7A11 and GPX4 partially inhibited by MPP+, and reduce MDA overproduction and lipid peroxidation to protect DA neurons. Nrf2 inhibitor ML385 could inhibit quercetin-induced increase of GPX4 and SLC7A11 protein expression, indicating that the protective effect of quercetin was mediated through Nrf2. CONCLUSIONS: The results of this study suggest that quercetin regulates ferroptosis through Nrf2-dependent signaling pathways, thereby inhibiting MPP+-induced neurotoxicity in SH-SY5Y/primary neurons.

Defect Healing of Micro/Nanocrystals via the Coordination Competition of Rare Earth in Crystal Engineering.

Defect engineering has been generally observed and utilized in crystal materials including metal oxides, metal-organic frameworks, and so on; however, how to relate the defect formation and crystallization process is needed to be revealed clearly, and how to heal the defect is a big challenge. Herein, based on the new coordination complex (HNU-53), the crystal defects were created by increasing the reaction time and crystal size. Following the crystal growth process, the crystal color centers were simultaneously generated, resulting in fluorescence quenching. To heal the defect, the crystal growth was controlled by the introduction of rare earth ions. With the coordination competition of rare earth ions, the crystal defects were reduced and recovery of fluorescence emission was achieved.

Creating Highly Active Iron Sites in Electrochemical N2 Reduction by Fabricating Strongly-Coupled Interfaces.

Electrochemical Nc reduction has been regarded as one of the most promising approaches to producing ammonia under mild conditions, but there are remaining pressing challenges in improving the reaction rate and efficiency. Herein, an unconventional galvanic replacement reaction is reported to fabricate a unique hierarchical structure composed of Fe3 O4 -CeO2 bimetallic nanotubes covered by Fe2 O3 ultrathin nanosheets. Control experiments reveal that CeO2 species play the essential role of stabilizer for Fe2+ cations. Compared with bare CeO2 and Fe2 O3 nanotubes, the as-obtained Fe2 O3 /Fe3 O4 -CeO2 possesses a remarkably enhanced NH3 yield rate (30.9 µg h-1 mgcat -1 ) and Faradaic efficiency (26.3%). The enhancement can be attributed to the hierarchical feature that makes electrodes more easily to contact with electrolytes. More importantly, as verified by density functional theory calculations, the generation of Fe2 O3 -Fe3 O4 heterogeneous junctions can efficiently optimize the reaction pathways, and the energy barrier of the potential determining step (the *N2 hydrogenates into *N*NH) is significantly decreased.

Space-confined growth of nanoscale metal-organic frameworks/Pd in hollow mesoporous silica for highly efficient catalytic reduction of 4-nitrophenol.

The development of confined growth of metal-organic frameworks (MOFs) in a nano-space remains a challenge mainly due to the spatial size randomness and inhomogeneity of host materials and the limitation of MOF species. In this study, we developed a general "stepwise vacuum evaporation" strategy, which allows the nano-confined growth of MOFs in hollow mesoporous silica nanospheres (HMSN) by the vacuum forces and the capillary effect. A series of nanoscale MOFs including ZIF-8, ZIF-90, HKUST-1, MIL-53(Cr) and UiO-66-NH2 were confinely synthesized inside the cavities of HMSN, resulting in hierarchically porous composites with core-shell structures. Further functionalization was studied by anchoring Pd to obtain UiO-66-NH2/Pd@HMSN catalyst, which exhibited excellent activity in the catalytic reduction of 4-nitrophenol to 4-aminophenol under ambient condition.

WSe2-loaded co-catalysts Cu3P and CNTs: Improving photocatalytic hydrogen precipitation and photocatalytic memory performance.

Photocatalytic decomposition of water for hydrogen production using semiconductor photocatalysts in visible light is considered one of the most promising environmentally friendly ways to produce hydrogen. In this work, the calcination method was adopted to prepare an efficient Cu3P/WSe2/CNTs composite photocatalysts. Cu3P and carbon nanotubes (CNTs) were used as co-catalysts to reduce the composite rate of the photogenerated supports of the photocatalyst. The unique metallic properties of Cu3P as a transition metal phosphide makes it a cost-effective alternative to noble metal co-catalysts. CNTs can serve both as co-catalysts and as a suitable carrier to accelerate the transfer rate of photogenerated electrons. The experimental results showed that the Cu3P/WSe2/CNTs composite photocatalyst exhibited stronger activities in photocatalytic hydrogen production than pure WSe2. In particular, a higher quantum yield of 30.27% at the range 400-700 nm was achieved with a loading of 4% CNTs, a calcination temperature of 300 °C and a calcination time of 2.0 h. In contrast, the quantum yield of pure WSe2 was only 14.01%. The highest hydrogen production rate was 6.987 mL in 4.0 h, and the average hydrogen production rate was 712.985 µmol·h-1g-1, which was 2.39 times higher than that of pure WSe2.The catalytic memory performance of the composite samples was also examined. The results indicated that the best catalytic memory performance was achieved under the pre-illumination condition of 5.0 h. The amount of hydrogen produced under darkness for 4.0 h was up to 4.934 mL and the average hydrogen production rate was 503.454 µmol·h-1g-1. The average hydrogen production rate was 1.69 times higher than the average hydrogen production rate of pure WSe2 under light conditions.

Ratiometric Fluorescent Sensor Based on Tb(III) Functionalized Metal-Organic Framework for Formic Acid.

Formic acid is a common chemical raw material, the effective detection of which is of importance to food safety and environmental quality. In this work, the lanthanide functionalized dual-emission metal-organic framework (TH25) was prepared as a ratiometric fluorescent sensor for formic acid. This ratiometric sensor has a good detection performance with high selectivity, sensitivity, and reproducibility. Together with a low limit of detection of 2.1 ppm, these characters promise the ability to sense at low levels as well as a practical detection ability. This work provides ideas for the design and synthesis of effective chemical sensors for organic acids.

The difference in red blood cell distribution width from before to after thrombolysis as a prognostic factor in acute ischemic stroke patients: A 2-year follow-up.

Purpose: The aim of our study was to determine whether delta red blood cell distribution (ΔRDW) improves neurological outcomes in acute ischemic stroke (AIS) patients 2 years after intravenous thrombolysis (IVT) therapy. Methods: AIS patients who received IVT between January 2013 and December 2019 were retrospectively analyzed. In accordance with their mRS scores, the patients were divided into two groups. A binary logistic regression analysis was conducted to determine the influencing factors of adverse functional outcomes. It was decided to evaluate the variables' the predictive ability by using the area under the receiver operating characteristic. For the poor neurological recovery risk model, features were selected using the LASSO regression model. We also developed a predictive model based on logistic regression analysis, which combined the features selected in the minimum absolute contraction and selection operator regression models. An evaluation of the discrimination, calibration, and clinical applicability of the predictive model was conducted using the C index, calibration chart, and decision curve analysis. Internal validation was evaluated via bootstrapping. Results: Binary logistic regression analysis showed that ΔRDW was an independent influencing factor for poor neurofunctional outcomes. The most appropriate ΔRDW cut-off value for predicting the recovery of poor neurological outcomes was 18.9% (sensitivity: 89.9%, specificity: 78.6%, p < 0.001). The predictive factors included in the nomogram were age, the occurrence of CHD, stroke, AF, ΔRDW, NIHSS score at onset, interval time from onset to IVT, and whether there were indwelling urine catheters and gastric tubes. The model has not only a good discrimination ability, which was indicated by an overall C index of 0.891 (95% confidence interval: 0.829-0.953), but also a considerable calibration ability. Decision curve analysis showed that the nomogram of adverse neurological outcomes recovery was useful in the clinical practice when intervention was implemented above the threshold of 1% possibility of adverse neurological outcomes recovery. Conclusion: In patients with AIS after thrombolysis, the ΔRDW is a potential influencing factor that can be readily used to predict the likelihood of poor neurological function recovery.

Efficient Photocatalytic Oxidative Coupling of Benzylamine over Uranyl-Organic Frameworks.

Visible-light-driven organic transformation photocatalyzed by metal-organic frameworks (MOFs) under mild conditions is considered a feasible route to conserve energy and simplify synthesis. Herein, a light-sensitized, three-dimensional uranyl-organic framework (HNU-64) with twofold interpenetration and its derivatives HNU-64-CH3 and HNU-64-Cl with functionalized ligands of -CH3 and -Cl groups were obtained. These MOFs have broad optical absorption bands and suitable band energy levels in photooxidation, which makes them exhibit high activity and selectivity for the photooxidation of benzylamine to N-benzylbenzoimide under mild conditions. This work provides an efficient and simple synthetic option for oxidative coupling of amines to directly produce imines.

Dye-Encapsulated Lanthanide-Based Metal-Organic Frameworks as a Dual-Emission Sensitization Platform for Alachlor Sensing.

As an important factor affecting global agricultural output, pesticides have a significant impact on the ecosystem. It is an urgent task to accurately and conveniently detect pesticide residues after their application. Herein, a fluorescent dye@MOF platform was designed via the encapsulation of rhodamine B (RhB) into the MOF structure (named RhB@HNU-48), which can significantly enhance the sensing sensitivity of alachlor with an ultralow detection limit of 0.59 ppb. The improved sensitivity of RhB@HNU-48 to pesticides was attributed to the host-guest interactions that affect the excitation and emission spectra of the composites. Based on the sensing capability of RhB@HNU-48, a logic gate was built to evaluate the safety level of alachlor residues in rivers and soil. The preparation of photofunctionalized MOF composites through modulation of host-guest interactions offers a promising strategy for the construction of desired sensors for agricultural residues.

Magnetic porphyrin-based metal organic gel for rapid RhB removal and enhanced antibacterial activity by heterogeneous Photo-Fenton reaction under visible light.

Nanomaterials with visible light-driven catalytic ability are beneficial in controlling environmental pollutants. Porphyrin-based metal organic gel (MOG) was herein synthesized in one step and magnetic metal organic gel (MMOG) was successfully prepared via in-situ reaction of MOG and Fe3O4. This MMOG was developed as a novel visible light assisted Fenton-like catalyst. The catalytic experiments showed the high photo-Fenton activity of MMOG in the degradation of Rhodamine B (RhB) in the presence of visible light and H2O2 with a RhB degradation efficiency of 94.2% within 40 min. Notably, the obtained MMOG can kill E. coli and S. aureus with high killing rate (>99.999%) under visible light. Importantly, the MMOG can be recovered simply by an external magnetic field due to the unique magnetic property. This easily synthesized MMOG with photo-Fenton activity under visible light and magnetic property makes MOG based on the photo-Fenton reaction a prospective material for the environmental and biomedical applications.

Diffusion Tensor Imaging Reveals Deep Brain Structure Changes in Early Parkinson's Disease Patients with Various Sleep Disorders.

Parkinson's disease (PD) is a progressive age-related movement disorder caused by dopaminergic neuron loss in the substantia nigra. Diffusion-based magnetic resonance imaging (MRI) studies­namely, diffusion tensor imaging (DTI)­have been performed in the context of PD, either with or without the involvement of sleep disorders (SDs), to deepen our understanding of cerebral microstructural alterations. Analyzing the clinical characteristics and neuroimaging features of SDs in early PD patients is beneficial for early diagnosis and timely invention. In our present study, we enrolled 36 early PD patients (31 patients with SDs and 5 patients without) and 22 healthy controls. Different types of SDs were assessed using the Rapid Eye Movement Sleep Behavior Disorder Questionnaire­Hong Kong, Epworth Sleepiness Scale, International Restless Legs Scale and PD Sleep Scale-2. Brain MRI examinations were carried out in all the participants, and a region-of-interest (ROI) analysis was used to determine the DTI-based fractional anisotropy (FA) values in the substantia nigra (SN), thalamus (Thal) and hypothalamus (HT). The results illustrate that SDs showed a higher prevalence in the early PD patients than in the healthy controls (86.11% vs. 27.27%). Early PD patients with nighttime problems (NPs) had longer courses of PD than those without (5.097 ± 2.925 vs. 2.200 ± 1.095; p < 0.05), and these patients with excessive daytime sleepiness (EDS) or restless legs syndrome (RLS) had more advanced Hoehn and Yahr stages (HY stage) than those without (1.522 ± 0.511 and 1.526 ± 0.513, respectively; both p < 0.05). Compared with the early PD patients without probable rapid eye movement sleep behavior disorder (pRBD), those with pRBD had longer courses, more advanced HY stages and worse motor and non-motor symptoms of PD (course(years), 3.385 ± 1.895 vs. 5.435 ± 3.160; HY stages, 1.462 ± 0.477 vs. 1.848 ± 0.553; UPDRS, 13.538 ± 7.333 vs. 21.783 ± 10.766; UPDRS, 6.538 ± 1.898 vs. 7.957 ± 2.345; all p < 0.05). In addition, the different number of SD types in early PD patients was significantly inversely associated with the severity of damage in the SN and HT. All of the early PD patients with various SDs had injuries in the SN, in whom the damage was more pronounced in patients with NP than those without. Moreover, early PD patients with NP, RLS or pRBD had worse degrees of HT damage than those without. The current study demonstrated the pathophysiological features and neuroimaging changes in early PD patients with various types of sleep disorders, which will help in early diagnosis and therapy.

Hispolon Methyl Ether, a Hispolon Analog, Suppresses the SRC/STAT3/Survivin Signaling Axis to Induce Cytotoxicity in Human Urinary Bladder Transitional Carcinoma Cell Lines.

Bladder cancer is a leading human malignancy worldwide. Signal transducer and activator of transcription (STAT) 3 is an oncogenic transcription factor commonly hyperactivated in most human cancers, including bladder cancer. Notably, preclinical evidence has validated STAT3 blockade as a promising therapeutic strategy for bladder cancer. Hispolon Methyl Ether (HME) is a structural analog of hispolon, an anticancer component of the medicinal mushroom Phellinus linteus. Thus far, HME's anticancer activity and mechanisms remain largely unknown. We herein report HME was cytotoxic, more potent than cisplatin, and proapoptotic to various human bladder transitional carcinoma cell lines. Of note, HME blocked STAT3 activation, evidenced by HME-elicited reduction in tyrosine 705-phosphorylated STAT3 levels constitutively expressed or induced by interleukin-6. Significantly, HME-induced cytotoxicity was abrogated in cells expressing a dominant-active STAT3 mutant (STAT3-C), confirming STAT3 blockage as a pivotal mechanism of HME's cytotoxic action. We further revealed that survivin was downregulated by HME, while its levels were rescued in STAT3-C-expressing cells. Moreover, survivin overexpression abolished HME-induced cytotoxicity, illustrating survivin as a central downstream mediator of STAT3 targeted by HME. Lastly, HME was shown to lower tyrosine 416-phosphorylated SRC levels, suggesting that HME inhibits STAT3 by repressing the activation of SRC, a STAT3 upstream kinase. In conclusion, we present the first evidence of HME's anti-bladder cancer effect, likely proceeding by evoking apoptosis through suppression of the antiapoptotic SRC/STAT3/survivin signaling axis.

Nuclear accumulation of KPNA2 impacts radioresistance through positive regulation of the PLSCR1-STAT1 loop in lung adenocarcinoma.

Lung adenocarcinoma (ADC) is the predominant histological type of lung cancer, and radiotherapy is one of the current therapeutic strategies for lung cancer treatment. Unfortunately, biological complexity and cancer heterogeneity contribute to radioresistance development. Karyopherin α2 (KPNA2) is a member of the importin α family that mediates the nucleocytoplasmic transport of cargo proteins. KPNA2 overexpression is observed across cancer tissues of diverse origins. However, the role of KPNA2 in lung cancer radioresistance is unclear. Herein, we demonstrated that high expression of KPNA2 is positively correlated with radioresistance and cancer stem cell (CSC) properties in lung ADC cells. Radioresistant cells exhibited nuclear accumulation of KPNA2 and its cargos (OCT4 and c-MYC). Additionally, KPNA2 knockdown regulated CSC-related gene expression in radioresistant cells. Next-generation sequencing and bioinformatic analysis revealed that STAT1 activation and nuclear phospholipid scramblase 1 (PLSCR1) are involved in KPNA2-mediated radioresistance. Endogenous PLSCR1 interacting with KPNA2 and PLSCR1 knockdown suppressed the radioresistance induced by KPNA2 expression. Both STAT1 and PLSCR1 were found to be positively correlated with dysregulated KPNA2 in radioresistant cells and ADC tissues. We further demonstrated a potential positive feedback loop between PLSCR1 and STAT1 in radioresistant cells, and this PLSCR1-STAT1 loop modulates CSC characteristics. In addition, AKT1 knockdown attenuated the nuclear accumulation of KPNA2 in radioresistant lung cancer cells. Our results collectively support a mechanistic understanding of a novel role for KPNA2 in promoting radioresistance in lung ADC cells.

Modulation of the Host-Guest-Guest Interactions in a Metal-Organic Framework for Multiple Anticounterfeiting Applications.

Developing fluorescent materials with multiple and tunable emissions under different conditions is necessary to meet the growing demand for optical anticounterfeiting technology. Different modes of fluorescence emission can be obtained by loading multiple fluorescent components into metal-organic frameworks (MOFs) and modulating the interaction among them for multiple anticounterfeiting purposes. Herein, a Cd-based MOF (HNU-60) was constructed as a host to encapsulate both lanthanide ions and carbon quantum dots. Multiple fluorescence emissions can be achieved by modulation of host-guest and guest-guest interaction, which holds promise for multiple anticounterfeiting applications. This work opens the opportunity to construct the hybrid MOF-based materials with controlled fluorescence properties for emerging anticounterfeiting applications in various fields.