The successful growth of colloidal lead halide perovskite quantum dots (PQDs) has generated tremendous interest in the community, due to the unique properties and the promise PQDs offer for use in ...applications involving light-emitting devices and solar cell technology. However, tangible progress in probing their fundamental properties and/or their integration into optoelectronic devices has been hampered by issues of colloidal and photophysical instability. Here, we introduce a promising surface coating strategy relying on a polyzwitterion polymer, where high-affinity binding onto the QDs is driven by multicoordinating electrostatic interactions with the ion-rich surfaces of CsPbBr3 PQDs. The polymer ligands were synthesized by installing a stoichiometric mixture of amine-modified sulfobetaine anchors and solubilizing motifs on poly(isobutylene-alt-maleic anhydride), PIMA, via nucleophilic addition reaction. We find that this coating approach imparts enhanced colloidal and photophysical stability to the nanocrystals over a broad range of solvent conditions and in powder form. This approach also allows easy phase transfer of the PQDs from nonpolar media to an array of solutions with varying polarities and properties. Additionally, the stabilization strategy preserves the photophysical and structural characteristics of the nanocrystals over a period extending to 1.5 years under certain conditions.
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IJS, KILJ, NUK, PNG, UL, UM
Mitochondrial reactive oxygen species (ROS) have emerged as an important mechanism of disease and redox signaling in the cellular system. Under basal or pathological conditions, electron leakage for ...ROS production is primarily mediated by complexes I and III of the electron transport chain (ETC) and by the proton motive force (PMF), consisting of a membrane potential (ΔΨ) and a proton gradient (ΔpH). Several factors control redox status in mitochondria, including ROS, the PMF, oxidative posttranslational modifications (OPTM) of the ETC subunits, SOD2, and cytochrome
heme lyase (HCCS). In the mitochondrial PMF, increased ΔpH-supported backpressure due to diminishing electron transport and chemiosmosis promotes a more reductive mitochondrial physiological setting. OPTM by protein cysteine sulfonation in complex I and complex III has been shown to affect enzymatic catalysis, the proton gradient, redox status, and enzyme-mediated ROS production. Pathological conditions associated with oxidative or nitrosative stress, such as myocardial ischemia and reperfusion (I/R), increase mitochondrial ROS production and redox dysfunction via oxidative injury to complexes I and III, intensely enhancing protein cysteine sulfonation and impairing heme integrity. The physiological conditions of reductive stress induced by gains in SOD2 function normalize I/R-mediated ROS overproduction and redox dysfunction. Further insight into the cellular mechanisms by which HCCS, biogenesis of
-type cytochrome, and OPTM regulate PMF and ROS production in mitochondria will enrich our understanding of redox signal transduction and identify new therapeutic targets for cardiovascular diseases in which oxidative stress perturbs normal redox signaling.
To look into the relationship between cardiac substructures (CS) dosimetric parameters and cardiac events (CE) or overall survival (OS) in patients undergoing radiation therapy (RT) for esophageal ...squamous cell carcinoma (ESCC).
A retrospective study included 350 patients with ESCC receiving definitive chemoradiotherapy or radiotherapy (d-CRT/d-RT) or neoadjuvant chemoradiotherapy (NCRT) from March 2013 to May 2022. Our study examined the adverse cardiac events of any grade or G3+, as defined by the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Competing risk analysis and Cox regression analysis were used to assess the relationship between CS doses and CEs or OS.
201 (57.4 %) patients received any grade CEs over a median follow-up time of 22.50 months (IQR, 12.40–45.60), and 24 (6.86 %) patients suffered G3+ CEs. On landmark analysis, patients with any grade CEs had significantly lower OS (P = 0.003). Multivariable analysis revealed that any grade CEs were predicted by the dose of CSs in all populations. In addition, for G3+ cardiac events, arrhythmic and small probability of cardiac events, LAD V20 ((HR: 1.02, 95 % CI: 1.00–1.03, P = 0.012; HR: 1.01, 95 % CI: 1.00–1.02, P = 0.005; HR; 1.01, 95 % CI: 1.00–1.02, P = 0.012) was also an independent predictive factor. LAD V50 (HR: 1.07, 95 % CI: 1.03–1.10, P <0.001) predicted pericardium effusion events. Moreover, the multivariable analysis revealed that OS was predicted by LAD V30 (HR: 1.03; 95 % CI, 1.01–1.05, P = 0.015).
In the population of ESCC patients receiving RT, we showed that the CS factors had a substantial predictive value for the various types and grades of CEs. The elevated radiation dose of LAD was a significant contributor to a higher rate of cardiac events and a worse prognosis.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
We have tested the ability of N-heterocyclic carbene (NHC)-modified ligands to coordinate and stabilize luminescent CdSe–ZnS core–shell quantum dot (QD) dispersions in hydrophilic media. In ...particular, we probed the effects of ligand structure and coordination number on the coating affinity to the nanocrystals. We find that such NHC-based ligands rapidly coordinate onto the QDs (requiring ∼5–10 min of reaction time), which reflects the soft Lewis base nature of the NHC groups, with its two electrons sharing capacity. Removal of the hydrophobic cap and promotion of carbene-driven coordination on the nanocrystals have been verified by 1H NMR spectroscopy, while 13C NMR was used to identify the formation of carbene–Zn complexes. The newly coated QD dispersions exhibit great long-term colloidal stability over a wide range of conditions. Additionally, we find that coordination onto the QD surfaces affects the optical and spectroscopic properties of the nanocrystals. These include a size-dependent red-shift of the absorption and fluorescence spectra and a pronounced increase in the measured fluorescence intensity when the samples are stored under white light exposure compared to those stored in the dark.
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IJS, KILJ, NUK, PNG, UL, UM
In this study, a novel core–shell magnetic fibrous nanocatalyst, Pd/Fe 3 O 4 @SiO 2 @KCC-1 with easily accessible active sites and a convenient recovery by applying an external magnetic field, was ...successfully developed. Fe 3 O 4 @SiO 2 @KCC-1 was functionalized with amino groups which act as robust anchors so that the palladium nanoparticles (Pd NPs) with an average diameter of about 4 nm were well-dispersed on the fibers of Fe 3 O 4 @SiO 2 @KCC-1 without obvious aggregation. The synthesized Pd/Fe 3 O 4 @SiO 2 @KCC-1 nanocatalyst exhibited excellent catalytic activity in the reduction of 4-nitrophenol by sodium borohydride, and the Suzuki cross coupling reactions of aryl chlorides with aryl boronic acids due to the easy accessibility of the active sites. Furthermore, the Pd/Fe 3 O 4 @SiO 2 @KCC-1 nanocatalyst was conveniently recovered by a magnet and could be reused for at least five cycles without significant loss in activity, thus confirming its good stability. Therefore, the abovementioned approach based on core–shell magnetic fibrous Fe 3 O 4 @SiO 2 @KCC-1 provided a useful platform for the fabrication of Pd NPs based catalysts with easy accessibility, superior activity and convenient recovery.
High tibial osteotomy (HTO) has been widely used for clinical treatment of osteoarthritis of the medial compartment of the knee, and both opening-wedge and closing-wedge HTO are the most commonly ...used methods. However, it remains unclear which technique has better clinical and radiological outcomes in practice. To systematically evaluate this issue, we conducted a comprehensive meta-analysis by pooling all available data for the opening-wedge HTO and closing-wedge HTO techniques from the electronic databases including PubMed, Embase, Wed of Science and Cochrane Library. A total of 22 studies encompassing 2582 cases were finally enrolled in the meta-analysis. There was no significant difference regarding surgery time, duration of hospitalization, knee pain VAS, Lysholm score and HSS knee score (clinical outcomes) between the opening-wedge and closing-wedge HTO groups (P > 0.05). However, the opening-wedge HTO group showed wider range of motion than the closing-wedge HTO group (P = 0.003). Moreover, as for Hip-Knee-Ankle angle and mean angle of correction, no significant difference was observed between the opening-wedge and closing-wedge HTO groups (P > 0.05), while the opening-wedge HTO group showed greater posterior tibial slope angle (P < 0.001) and lesser patellar height than the closing-wedge HTO group (P < 0.001). On light of the above analysis, we believe that individualized surgical approach should be introduced based on the clinical characteristics of each patient.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
CCRT is presently the standard treatment for LA-NSCLC. RP is one of the main obstacles to the completion of thoracic radiation therapy, resulting in limited survival benefits in NSCLC patients. This ...research aims to explore the role of Endostar in the occurrence of grade≥2 RP and clinical curative effect in LA-NSCLC patients.
This study retrospectively analyzed 122 patients with stage III NSCLC who received CCRT from December 2008 to December 2017, or Endostar intravenous drip concurrently with chemoradiotherapy (Endostar + CCRT group). Standard toxicity of the pneumonitis endpoint was also collected by CTCAE V5.0. We further summarized other available studies on the role of Endostar in the prognosis of NSCLC patients and the incidence of RP.
There were 76 cases in the CCRT group and 46 cases in the CCRT+ Endostar group. In the CCRT+ Endostar group, the occurrence of grade ≥2 RP in patients with V20Gy ≥25% was significantly higher than that in patients with V20Gy < 25% (p = 0.001). In the cohorts with V20Gy < 25%, 0 cases of 29 patients treated with Endostar developed grade ≥2 RP was lower than in the CCRT group (p = 0.026). The re-analysis of data from other available studies indicated that Endostar plus CCRT could be more efficient and safely in the occurrence of grade≥2 RP with LA-NSCLC.
When receiving CCRT for LA-NSCLC patients, simultaneous combination of Endostar is recommended to enhance clinical benefit and reduce pulmonary toxicity.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Cancer cells often require glutamine for growth, thereby distinguishing them from most normal cells. Here we show that PIK3CA mutations reprogram glutamine metabolism by upregulating glutamate ...pyruvate transaminase 2 (GPT2) in colorectal cancer (CRC) cells, making them more dependent on glutamine. Compared with isogenic wild-type (WT) cells, PIK3CA mutant CRCs convert substantially more glutamine to α-ketoglutarate to replenish the tricarboxylic acid cycle and generate ATP. Mutant p110α upregulates GPT2 gene expression through an AKT-independent, PDK1-RSK2-ATF4 signalling axis. Moreover, aminooxyacetate, which inhibits the enzymatic activity of aminotransferases including GPT2, suppresses xenograft tumour growth of CRCs with PIK3CA mutations, but not with WT PIK3CA. Together, these data establish oncogenic PIK3CA mutations as a cause of glutamine dependency in CRCs and suggest that targeting glutamine metabolism may be an effective approach to treat CRC patients harbouring PIK3CA mutations.
Hypothyroidism causes somatic, psychosocial and affective psychosis, including depression-like behaviors. In this study, (hypothyroidism group; HP group) adult male Sprague Dawley (SD) rats were ...induced to hypothyroidism after 5 weeks of exposure to 0.05% propylthiouracil (PTU) in potable water, control animals (CON group) were given the same amount of water. The following behavioral experiments were conducted, respectively: open-field test (OFT), forced swimming test (FST), tail suspension test (TST). TT
3
and TT
4
levels were measured after the behavior tests and the expression levels of 5-HT
2
A
receptor and 5-HT
2
A
receptor proteins were analyzed in the hippocampus and prefrontal cortex. The level of TT
3
and TT
4
in the HP group rats was much lower than that in the CON group. The hypothyroid rats also showed weight loss, much longer immobility time in tail suspension test and forced swimming test. Besides, 5 weeks of PTU administration was associated with significantly decreased expression levels of 5-HT
2
A
receptor and 5-HT
2
A
receptor proteins compared with control group, which were significantly negatively correlated with immobility time in FST and TST. In conclusion, our results suggest that hypothyroidism induces depressive behaviors through the influence of the serotonin system, and the decreased expression of the 5-HT
2
A
receptor is an important cause of the depressive behaviors in hypothyroidism.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, ODKLJ, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Immunotherapies, such as immune checkpoint inhibitors (ICIs) and chimeric antigen receptor (CAR) T cells, have revolutionized the treatment of patients with advanced and metastatic tumors resistant ...to traditional therapies. However, the immunosuppressed tumor microenvironment (TME) results in a weak response to immunotherapy. Therefore, to realize the full potential of immunotherapy and obstacle barriers, it is essential to explore how to convert cold TME to hot TME. Autophagy is a crucial cellular process that preserves cellular stability in the cellular components of the TME, contributing to the characterization of the immunosuppressive TME. Targeted autophagy ignites immunosuppressive TME by influencing antigen release, antigen presentation, antigen recognition, and immune cell trafficking, thereby enhancing the effectiveness of cancer immunotherapy and overcoming resistance to immunotherapy. In this review, we summarize the characteristics and components of TME, explore the mechanisms and functions of autophagy in the characterization and regulation of TME, and discuss autophagy-based therapies as adjuvant enhancers of immunotherapy to improve the effectiveness of immunotherapy.
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