Brusatol hinders the progression of bladder cancer by Chac1/Nrf2/SLC7A11 pathway.

Bladder cancer is a common tumor that impacts the urinary system and marked by a significant fatality rate and an unfavorable prognosis. Promising antineoplastic properties are exhibited by brusatol, which is obtained from the dried ripe fruit of Brucea javanica. The present study aimed to evaluate the influence of brusatol on the progression of bladder cancer and uncover the molecular mechanism involved. We used Cell Counting Kit-8, colony formation and EdU assays to detect cell numbers, viability and proliferation. We used transwell migration assay to detect cell migration ability. The mechanism of brusatol inhibition of bladder cancer proliferation was studied by flow cytometry and western blotting. It was revealed that brusatol could reduce the viability and proliferation of T24 and 5637 cells. The transwell migration assay revealed that brusatol was able to attenuate the migration of T24 and 5637 cells. We found that treatment with brusatol increased the levels of reactive oxygen species, malondialdehyde and Fe2+, thereby further promoting ferroptosis in T24 and 5637 cells. In addition, treatment with RSL3 (an agonistor of ferroptosis) ferrostatin-1 (a selective inhibitor of ferroptosis) enhanced or reversed the brusatol-induced inhibition. In vivo, treatment with brusatol significantly suppressed the tumor growth in nude mice. Mechanistically, brusatol induced ferroptosis by upregulating the expression of ChaC glutathione-specific gamma-glutamylcyclotransferase (Chac1) and decreasing the expression of SLC7A11 and Nrf2 in T24 and 5637 cells. To summarize, the findings of this research demonstrated that brusatol hindered the growth of bladder cancer and triggered ferroptosis via the Chac1/Nrf2/SLC7A11 pathway.

A Music-Driven Dance Generation Method Based on a Spatial-Temporal Refinement Model to Optimize Abnormal Frames.

Since existing music-driven dance generation methods have abnormal motion when generating dance sequences which leads to unnatural overall dance movements, a music-driven dance generation method based on a spatial-temporal refinement model is proposed to optimize the abnormal frames. Firstly, the cross-modal alignment model is used to learn the correspondence between the two modalities of audio and dance video and based on the learned correspondence, the corresponding dance segments are matched with the input music segments. Secondly, an abnormal frame optimization algorithm is proposed to carry out the optimization of the abnormal frames in the dance sequence. Finally, a temporal refinement model is used to constrain the music beats and dance rhythms in the temporal perspective to further strengthen the consistency between the music and the dance movements. The experimental results show that the proposed method can generate realistic and natural dance video sequences, with the FID index reduced by 1.2 and the diversity index improved by 1.7.

Suppressing Phase Segregation in CsPbIBr2 Films via Anchoring Halide Ions toward Underwater Solar Cells.

Inorganic CsPbIBr2 perovskite solar cells (PSCs) have accomplished many milestones, yet their progress has been constrained by ion migration and phase separation. This study explores the modulation of perovskite crystallization kinetics and halide ion migration through chlorobenzene (CB) antisolvent with bis(pentafluorophenyl)zinc (Zn(C6F5)2) additive. The photoluminescence and absorption spectra reveal the significantly reduced phase segregaton in CsPbIBr2 film treated by CB with Zn(C6F5)2. Moreover, this research analyzes the CsPbIBr2 film's free carrier lifetime, diffusion length, and mobility using time-resolved microwave conductivity and transient absorption spectroscopy after Zn(C6F5)2 modification. Consequently, the modified CsPbIBr2 PSCs offer a 12.57% power conversion efficiency (PCE), the highest value among CsPbIBr2 PSCs with negligible hysteresis and prolonged stability. Furthermore, under 1-m-deep water, CsPbIBr2 PSCs display a PCE of 14.18%. These findings provide an understanding of the development of phase-segregation-free CsPbIBr2 films and showcase the prospective applications of CsPbIBr2 PSCs in underwater power systems.

Multidentate Chelation Achieves Bilateral Passivation toward Efficient and Stable Perovskite Solar Cells with Minimized Energy Losses.

Defects in the electron transport layer (ETL), perovskite, and buried interface will result in considerable nonradiative recombination. Here, a bottom-up bilateral modification strategy is proposed by incorporating arsenazo III (AA), a chromogenic agent for metal ions, to regulate SnO2 nanoparticles. AA can complex with uncoordinated Sn4+/Pb2+ in the form of multidentate chelation. Furthermore, by forming a hydrogen bond with formamidinium (FA), AA can suppress FA+ defects and regulate crystallization. Multiple chemical bonds between AA and functional layers are established, synergistically preventing the agglomeration of SnO2 nanoparticles, enhancing carrier transport dynamics, passivating bilateral defects, releasing tensile stress, and promoting the crystallization of perovskite. Ultimately, the AA-optimized power conversion efficiency (PCE) of the methylammonium-free (MA-free) devices (Rb0.02(FA0.95Cs0.05)0.98PbI2.91Br0.03Cl0.06) is boosted from 20.88% to 23.17% with a high open-circuit voltage (VOC) exceeding 1.18 V and ultralow energy losses down to 0.37 eV. In addition, the optimized devices also exhibit superior stability.

Additive Conformational Engineering To Improve the PbI2 Framework for Efficient and Stable Perovskite Solar Cells.

The PbI2 framework is critical for two-step fabricated perovskite solar cells. This study investigates the effects of introducing two functional urea-based molecules, biuret (BU) and dithiobiuret (DTBU), into the PbI2 precursor solution on the absorber layer and overall device performance. BU, which contains C═O, enhanced device performance and stability, whereas DTBU, which contains C═S, had negative effects. Research analysis revealed the differences in the spatial structures of the two urea-based molecules. The introduction of symmetrical BU molecules facilitated the crystallization of PbI2, whereas the introduction of DTBU with a twisted molecular structure led to inferior crystallization performance of PbI2. The perovskite thin film, obtained by introducing BU into the PbI2 precursor solution, demonstrated superior performance, characterized by a decreased defect density and an extended carrier lifetime. The device performance and stability were enhanced, resulting in higher open-circuit voltage and fill factor. The highest achieved power conversion efficiency was 23.50%. After 1300 h of storage under unpackaged conditions at 30-40% humidity, the devices maintained 93% of their initial efficiency. Conversely, the devices prepared with DTBU doping exhibited inferior performance and stability, displaying power conversion efficiency below 10% and faster degradation under the same humidity conditions.

Detecting phosphate using lysine-sensitized terbium coordination polymer nanoparticles as ratiometric luminescence probes.

Probes for detecting phosphate ions (Pi) are required for environmental monitoring and to protect human health. Here, novel ratiometric luminescent lanthanide coordination polymer nanoparticles (CPNs) were successfully prepared and used to selectively and sensitively detect Pi. The nanoparticles were prepared from adenosine monophosphate (AMP) and Tb3+, and lysine (Lys) was used as a sensitizer (through the antenna effect) to switch on Tb3+ luminescence at 488 and 544 nm while Lys luminescence at 375 nm was quenched because of energy transfer from Lys to Tb3+. The complex involved is here labeled AMP-Tb/Lys. Pi destroyed the AMP-Tb/Lys CPNs and therefore decreased the AMP-Tb/Lys luminescence intensity at 544 nm and increased the luminescence intensity at 375 nm at an excitation wavelength of 290 nm, meaning ratiometric luminescence detection was possible. The ratio between the luminescence intensities at 544 and 375 nm (I544/I375) was strongly associated with the Pi concentration between 0.1 and 6.0 µM, and the detection limit was 0.08 µM. The dual-emission reverse-change ratio luminescence sensing method can exclude environmental effects, so the proposed assay was found to be very selective. The method was successfully used to detect Pi in real water samples, and acceptable recoveries were found, suggesting that the method could be used in practice to detect Pi in water samples.

High-performance lead-free quaternary antiperovskite photovoltaic candidate Ca6N2AsSb.

Accurate many-body perturbation theory-based calculations were used to study the electronic and excitonic properties of lead-free quaternary antiperovskite Ca6N2AsSb; large quasiparticle band gap renormalization, strong optical absorption, and low exciton binding energy, as well as high efficiency of >32% with a thickness of 500 nm were predicted.

Dendrimer-conjugated isotretinoin for controlled transdermal drug delivery.

BACKGROUND: In the present study, we aimed to develop a novel isotretinoin delivery model for treating skin diseases, revealing its potential advantages in drug delivery and targeted therapy. Using a self-assembly strategy, we grafted a dendrimer, based on a well-defined branched structure for nanomedical devices, with a well-defined nanoarchitecture, yielding spherical, highly homogeneous molecules with multiple surface functionalities. Accordingly, a self-assembled dendrimer-conjugated system was developed to achieve the transdermal delivery of isotretinoin (13cRA-D). RESULTS: Herein, 13cRA-D showed remarkable controlled release, characterized by slow release in normal tissues but accelerated release in tissues with low pH, such as sites of inflammation. These release characteristics could abrogate the nonteratogenic side effects of isotretinoin and allow efficient skin permeation. Moreover, 13cRA-D exhibited high therapeutic efficacy in acne models. Based on in vitro and in vivo experimental results, 13cRA-D afforded better skin penetration than isotretinoin and allowed lesion targeting. Additionally, 13cRA-D induced minimal skin irritation. CONCLUSION: Our findings suggest that 13cRA-D is a safe and effective isotretinoin formulation for treating patients with skin disorders.

Ratiometric fluorescence nanoprobe based on carbon dots and terephthalic acid for determining Fe2+ in environmental samples.

A ratiometric fluorescent nanoprobe using carbon dots (CDs) and involving oxidation of terephthalic acid (TPA) induced by hydroxyl radicals (·OH) was developed for sensitively and selectively determining Fe2+ ions. When Fe2+ ions are added to the TPA@CDs/H2O2 system, ·OH produced through the Fenton reaction oxidizes the non-fluorescent TPA to give 2-hydroxyl terephthalic acid, which fluoresces at 423 nm when excited at 286 nm. The ·OH and Fe3+ produced quench CD fluorescence at 326 nm. The 2-hydroxyl terephthalic acid to CD fluorescence intensity ratio linearly increased as the Fe2+ concentration increased in the range 0.5-50 µM, and the detection limit was 0.25 µM. The new assay is very selective because it involves dual-emission reverse change ratio fluorescence sensing, which can exclude matrix effects. The new nanoprobe was used to determine Fe2+ concentrations in real water samples, and the recoveries were found to be acceptable. Schematic of the ratiometric fluorometric method for determining Fe2+ based on CDs and TPA.

Sexual hormones in a coastal river adjacent to the Bohai Sea: Characteristic pollutants and dominantly influencing factors.

Characteristic sexual hormones (SHs) and the factors that dominantly influence their occurrence in coastal ecosystems are less understood. This study verified the relationships between SHs and environmental factors and further inferred the possible controlling mechanisms of SH distribution. A characteristic pollutant of SHs was first proposed by determining the contamination level and ecological risks of SHs (seven species) in a coastal river adjacent to the Bohai Sea. The results showed that the 17ß-oestradiol (17ß-E2), estriol (E3), and 17α-ethynylestradiol (EE2) had high mean concentrations of 11.20 (±1.31), 10.17 (±4.91), and 16.71 (±0.88) ng L-1, respectively, in the river water. The concentration of estrone (E1) was positively related to microbial substances of DOMs (p < 0.05). The humification index (HIX) had a negative relationship with E3 (p < 0.05). In water, the distribution of total SHs was regulated by the HIX and fluorescence index (FI), which might be related to photodegradation reactions. The 17α-oestradiol (17α-E2) and EE2 were related to humified organic matter, while E3 and androstenedione (ADD) were influenced by sewage input. The 17ß-E2, E1, and 17α-E2 may be derived from animal sources, while E3, ADD, EE2, and progesterone were from human activities. Oestrogens, including E1, 17α-E2, 17ß-E2, and EE2, displayed higher ecological risks than androgens and progesterone, with medium to high risk in most sites. The 17ß-E2 was regarded as a characteristic pollutant of SHs throughout the river system, which displayed the highest risk. This paper may provide a reference for SH risk management and control.

Ratiometric fluorescence and smartphone dual-mode detection of glutathione using carbon dots coupled with Ag+-triggered oxidation of o-phenylenediamine.

Developing ratiometric fluorescence and smartphone dual-mode bioanalysis methods is important but challenging. A ratiometric fluorescence method for determining glutathione (GSH) using carbon dots (CDs) and Ag+-triggered o-phenylenediamine (OPD) oxidation is described here. Ag+oxidizes OPD to give 2,3-diaminophenazine (oxOPD), which effectively quenches CD fluorescence at 436 nm through the inner filter effect and causes a new emission peak at 561 nm. GSH chelates with Ag+and prevents the Ag+oxidizing OPD and therefore effectively preserves CD emission at 436 nm (blue) and allows only weak oxOPD fluorescence at 561 nm (orange) to occur. The oxOPD to CD fluorescence intensity ratio decreased linearly as the GSH concentration increased in the range 0-150 nM, and the detection limit was 15 nM. The ratiometric fluorescence probe lit with an ultraviolet lamp clearly changed color from orange to blue as the GSH concentration increased. An image was acquired using a smartphone camera and converted into digital values. The blue and red channel ratio was calculated and used to quantify GSH. The method therefore allows dual-mode detection of GSH.

Sensitive detection of picric acid in an aqueous solution using fluorescent nonconjugated polymer dots as fluorescent probes.

Nonconjugated polymer dots (NPDs) were successfully used as fluorescent probes to selectively and sensitively detect picric acid (PA). The NPDs were prepared from polyethylenimine and 1,4-phthalaldehyde under mild conditions and had excitation and emission maxima of 351 and 474 nm, respectively. Fluorescence of the NPDs was efficiently quenched by PA through the inner filter effect because of the overlapping PA absorption band and NPD excitation spectrum. The NPDs allowed PA to be determined with a high degree of sensitivity. The linear range was 0-140µM and the detection limit was 0.5µM. The work involved developing a novel method for synthesizing NPDs and a promising platform for determining PA in environmental media.

Morphologic Features of Symptomatic and Ruptured Abdominal Aortic Aneurysm in Asian Patients.

BACKGROUND: To evaluate morphologic features of symptomatic and ruptured abdominal aortic aneurysms in Asian patients. METHODS: Two hundred sixty four continuous candidates with an abdominal aortic aneurysm (AAA) were retrospectively identified from a tertiary hospital database between January 2017 and May 2019. The patients meeting inclusion criteria were divided into symptomatic or ruptured AAA (srAAA) and asymptomatic AAA (asAAA) groups. Their computed tomography angiographies were reconstructed using centerline technique and the geometric features of AAAs between the 2 groups were compared. RESULTS: One hundred two patients fulfilled selection criteria (mean age 71 years, 80 men), comprising 35 srAAAs and 67 asAAAs. There was no essential association between gender, smoking or hypertension, and AAA-associated symptoms or rupture. The maximum diameter (5.8 ± 1.4 cm vs. 5.0 ± 0.9 cm; P = 0.001), length (8.8 ± 0.6 cm vs. 7.0 ± 0.3 cm; P = 0.002), and intraluminal thrombus (ILT) thickness (1.7 ± 0.2 cm vs. 1.3 ± 0.1 cm; P = 0.039) of AAAs were independent risk factors for AAA-associated symptoms or rupture (binary logistic regression, P < 0.05), but AAA length and ILT were strongly correlated with the AAA diameter (Pearson correlation coefficient value of 0.591 and 0.444) whereas other factors such as aneurysmal tortuosity, aneurysmal neck anatomy, or common iliac artery geometry were nonsignificant. CONCLUSIONS: AAA diameter, length, and intraluminal thrombus thickness were identified as risk factors for AAA-associated symptoms in Asian patients. While the diameter is regarded as the most important predictor for symptoms and rupture, AAA length and ILT thickness should also be taken into consideration when contemplating intervention, particularly for borderline and smaller aneurysms.

Porous Nanosheet Assembly for Macrocyclization and Self-Release.

Macrocyclic structures are challenging synthetic targets owing to various potential applications ranging from drug discovery to nanomaterials. Their use, however, is highly limited due to synthetic difficulties arising from an entropic penalty for folding of linear chains. Here, we report single-layered porous nanosheets with 2D ordered internal cavities that act as a highly efficient macrocycle generator, changing linear substrates to release as macrocycles in aqueous methanol solution. The nanosheets with hydrophobic cavities encapsulate a linear substrate with nearly perfect uptake, perform clean cyclization, and then spontaneously release as a pure macrocycle. The self-separation of the macrocycle that precipitates from the solution leads to repeated cycles of macrocycle generation; thereby, the single-layered porous materials enabling catch and release offer a powerful novel strategy for repeated macrocycle generation.

Switching between Stacked Toroids and Helical Supramolecular Polymers in Aqueous Nanotubules.

Although significant advances have been made in supramolecular tubules, reversible polymerization in the tubular walls while maintaining their intact structure remains a great challenge. Here, reversible helical supramolecular polymerization of stacked toroids is reported, while maintaining tubular structures in aqueous solution. At room temperature, the tubules consist of discrete toroid stackings with hydrophobic interior. Upon heating, the tubules based on toroid stackings undergo a reversible helical supramolecular polymerization to transform into helical tubules by interconnecting between spirally open toroids. The helical polymerization arises from a tilting transition of the closed toroids that transform into spirally open toroids driven by the thermal dehydration of a hydrophilic oligoether dendron surrounding the toroid frameworks.

The molecular mechanism underlying GABAergic dysfunction in nucleus accumbens of depression-like behaviours in mice.

Depression is the most frequent psychiatric disorder in the world. Recent evidence has shown that stress-induced GABAergic dysfunction in the nucleus accumbens (NAc) contributed to the pathophysiology of depression. However, the molecular mechanisms underlying these pathological changes remain unclear. In this study, mice were constantly treated with the chronic unpredictable mild stress (CUMS) till showing depression-like behaviours expression. GABA synthesis, release and uptake in the NAc tissue were assessed by analysing the expression level of genes and proteins of Gad-1, VGAT and GAT-3 by qRT-PCR and Western blotting. The miRNA/mRNA network regulating GABA was constructed based on the bioinformatics prediction software and further validated by dual-luciferase reporter assay in vitro and qRT-PCR in vivo, respectively. Our results showed that the expression level of GAT-3, Gad-1 and VGAT mRNA and protein significantly decreased in the NAc tissue from CUMS-induced depression-like mice than that of control mice. However, miRNA-144-3p, miRNA-879-5p, miR-15b-5p and miRNA-582-5p that directly down-regulated the expression of Gad-1, VGAT and GAT-3 were increased. In the mRNA/miRNA regulatory GABA network, Gad-1 and VGAT were directly regulated by binding seed sequence of miR-144-3p, and miR-15b-5p, miR-879-5p could be served negative post-regulators by binding to the different sites of VGAT 3'-UTR. Chronic stress causes the impaired GABA synthesis, release and uptake by up-regulating miRNAs and down-regulating mRNAs and proteins, which may reveal the molecular mechanisms for the decreased GABA concentrations in the NAc tissue of CUMS-induced depression.

Substrate-Driven Transient Self-Assembly and Spontaneous Disassembly Directed by Chemical Reaction with Product Release.

The chemical reactivity of molecules can be significantly enhanced when they are trapped in a confined space. Although such a confinement effect can be found in many self-assembled nanostructures, dissipation after completing the reaction to release the product remains elusive. Here we report substrate-directed transient self-assembly for accelerating a chemical reaction and spontaneous disassembly with releasing the products. The hydrophobic substrates mediate self-assembly of a dissolved pyridine-based amphiphile to provide a confined space to promote an aromatic nucleophilic substitution (SNAr) reaction in water. The chemical reaction triggers disassembly of the aggregates with simultaneous release of the product that can be spontaneously separated out of the solution by precipitation. Neutralization of the amphiphilic molecule leads to a new cycle of self-assembly entrapping substrates and disassembly with releasing the product.

Homochiral porous nanosheets for enantiomer sieving.

Protein pores are highly specific in binding to chiral substrates and in catalysing stereospecific reactions, because their active pockets are asymmetric and stereoselective1,2. Chiral binding materials from molecular-level pores with high specificity have not been achieved because of problems with pore deformation and blocking 3 . A promising solution is the self-assembly of single sheets where all pores are exposed to the environment, for example as metal-organic frameworks 4 , polymers5,6 or non-covalent aromatic networks7-10, but, typically, the pores are distant from the internal cavities with chirality. Here, we report the synthesis of homochiral porous nanosheets achieved by the 2D self-assembly of non-chiral macrocycles, with open/closed pore switching. Pore chirality is spontaneously induced by a twisted stack of dimeric macrocycles. The porous 2D structures can serve as enantiomer sieving membranes that exclusively capture a single enantiomer in a racemic mixture solution, with uptake capacity greater than 96%. Moreover, the entrapped guests inside the pores can be pumped out by pore closing triggered by external stimuli. This strategy could provide new opportunities for controlled molecule release, as well as for artificial cells.

MiR-5100 promotes osteogenic differentiation by targeting Tob2.

MicroRNAs have emerged as pivotal regulators in various physiological and pathological processes, including osteogenesis. Here we discuss the contribution of miR-5100 to osteoblast differentiation and mineralization. We found that miR-5100 was upregulated during osteoblast differentiation in ST2 and MC3T3-E1 cells. Next, we verified that miR-5100 can promote osteogenic differentiation with gain-of-function and loss-of-function experiments. Target prediction analysis and experimental validation demonstrated that Tob2, which acts as a negative regulator of osteogenesis, was negatively regulated by miR-5100. Furthermore, we confirmed that the important bone-related transcription factor osterix, which can be degraded by binding to Tob2, was influenced by miR-5100 during osteoblast differentiation. Collectively, our results revealed a new molecular mechanism that fine-tunes osteoblast differentiation through miR-5100/Tob2/osterix networks.

Dissolved nitrous oxide and emission relating to denitrification across the Poyang Lake aquatic continuum.

Most aquatic ecosystems contribute elevated N2O to atmosphere due to increasing anthropogenic nitrogen loading. To further understand the spatial heterogeneity along an aquatic continuum from the upriver to wetland to lake to downriver, the study was conducted on spatial variations in N2O emission along Poyang Lake aquatic continuum during the flood season from 15 July 2013 to 10 August 2013. The results showed the N2O concentrations, the ratio of N2O/dinitrogen (N2) gases production, N2O emission and denitrification rates ranged from 0.10 to 1.11µgN/L, -0.007% to 0.051%, -9.73 to 127µgN/m2/hr and 1.33×104 to 31.9×104µgN2/m2/hr, respectively, across the continuum. The average N2O concentrations, the ratio of N2O/N2 and N2O emission was significantly lower in wetlands as compared to the rivers and lake (p<0.01). The significantly high denitrification rate and low N2O emission together highlighted that most N2O can be converted into N2 via near complete denitrification in the Poyang Lake wetlands. Our study suggests that the wetlands might impact N2O budget in an integrated aquatic ecosystems. Moreover, N2O emission from different aquatic ecosystem should be considered separately when quantifying the regional budget in aquatic ecosystem.