Browse Articles

Structure‐Informed Design of Distinct Parallel G‐Quadruplex Stabilizers for <i>KRAS</i> ‐Driven Cancer Therapy

ABSTRACT Targeting oncogene promoter G‐quadruplexes (G4s) is a compelling therapeutic strategy against human malignancies. However, clinical progress has been hindered by the lack of potent and structurally diverse G4‐targeting ligands. Herein, using parallel KRAS proximal promoter G4 ( KRAS ‐G4) as a model system, we screened an in‐house natural product library and identified dehydroevodiamine (DEE) as a novel G4 stabilizer. Although DEE showed only modest anticancer activity, structural analyses determined its predominant binding mode to KRAS ‐G4. Leveraging these structural insights, we rationally designed and synthesized 15 DEE analogues. Among them, compound 7i emerged as the lead candidate, demonstrating a 9‐fold higher binding affinity and up to 20‐fold improvement in antiproliferative activity over DEE. We further determined the high‐resolution NMR structure of the KRAS ‐G4– 7i complex, uncovering a distinct dual‐binding mode, featuring extensive π–π stacking interactions with outer G‐tetrads and specific hydrogen bonding within groove regions. Functional analysis showed 7i effectively suppressed transcription of several G4‐containing oncogenes, induced genome‐wide G4 formation, and triggered DNA damage in colorectal cancer cells. Moreover, 7i significantly inhibited the growth of patient‐derived colorectal tumor organoids. Overall, our findings establish a structural framework for rational design of parallel G4‐targeting ligands and emphasize an alternative G4‐based therapeutic strategy for KRAS ‐driven cancers.

Breast cancer risk factors, molecular subtypes and diagnosis in Bangladeshi women: insights from a case-control study of 290 participants

Knowledge, attitudes and practices regarding the environmental implications of pet ownership in Hong Kong

Deep learning for assessing corneal endothelial cell density in patients after descemet membrane endothelial keratoplasty: towards improved evaluation

Simple‐Synthesis Isomer‐Free Multi‐Adduct Fullerenes as Electron Transport Materials Enable 26.66% Efficiency of Perovskite Solar Cells

ABSTRACT The laggard advancement in electron transport layer materials is one of the bottleneck problems, impeding the further improvement of photovoltaic performance of perovskite solar cells (PSCs). Fullerene derivatives are widely used as electron transport layer materials for PSCs, but significant imperfections remain unresolved. Herein, an efficient and facile method was developed to prepare isomer‐free multi‐adduct fullerene derivatives, C 60 (NHR) 4 O, with high yield and meet the multifunctional requirements of electron transport layer materials of PSCs. Among the multi‐adduct fullerene derivatives, tetra[methyl 2‐amino‐3‐(thiophen‐2‐yl)propanoate]C 60 epoxide (TATPC) was selected to incorporate into PCBM as an electron transport material for PSCs. Benefiting from multi‐adduct groups, TATPC presents a higher LUMO energy level, superior passivation capability, and stronger interaction with perovskite than the classical PCBM. It enables PCBM:TATPC to afford improved coverage and a smoother surface, increased contact potential difference, reduced trap density, higher electron mobility, and inhibited self‐aggregation, thus facilitating electron extraction, suppressing charge carrier recombination, and enhancing durability for PSCs. Therefore, PCBM:TATPC‐based PSCs achieve an impressive efficiency of 26.66% (25.81% for devices with an area of 1.04 cm 2 ) with enhanced operational stability. This work highlights an efficient molecular design strategy to develop isomer‐free multi‐adduct fullerenes and thus regulate the electron transport layer for high‐efficiency and stable PSCs.

Multi-algorithm consensus clustering identifies four subphenotypes in sepsis-associated acute kidney injury

Elevated lipoprotein(a), trimethylamine n-oxide, and gut dysbiosis are associated with subclinical coronary atherosclerosis independent of metabolic dysfunction-associated steatotic liver disease

Hybrid Seeding‐Template Modulation of Sn–Pb Perovskite Crystallization for High‐Efficiency All‐Perovskite Tandem Solar Cells

ABSTRACT Narrow‐bandgap (NBG) Sn–Pb perovskites are indispensable for achieving high‐efficiency all‐perovskite tandem solar cells (TSCs). However, the pronounced disparity in the Lewis acidity of Sn 2+ and Pb 2+ often causes asynchronous nucleation and uncontrolled crystallization, severely limiting the device performance. Here, we propose a hybrid heterogeneous seeding and growth‐template strategy that integrates CsPbBr 3 quantum dots (QDs) with porous UiO‐66 metal–organic frameworks (MOFs) through grafted poly(4‐vinylpyridine) (P4VP) to achieve homogenous Sn–Pb perovskite films. Specifically, the embedded CsPbBr 3 QDs act as abundant nucleation centers, lowering the energy barrier and providing an epitaxial growth template, while the carbonyl (C═O) groups of UiO‐66 ligands and the imine (C═N) moieties of P4VP coordinate with Sn 2+ /Pb 2+ to finely regulate crystallization kinetics. Moreover, the UiO‐66‐P4VP framework functions as a scaffold to promote uniform film growth, resulting in Sn–Pb perovskite films with homogeneous composition and reduced defect density. As a result, the optimized single‐junction NBG perovskite solar cell achieves a fill factor exceeding 81% and a power conversion efficiency (PCE) of 23.32%. Furthermore, the two‐terminal all‐perovskite tandem device delivers a PCE of 29.18% and retains 80% of its initial efficiency after 500 h of continuous maximum power point tracking under simulated sunlight, demonstrating remarkable operational stability.

Sex-dependent alterations in motor cortex after spinal cord injury and implications in neurodegeneration risk

Fuzzy based residual shufflenet based breast cancer detection using mammogram images

Abstract Breast cancer is a condition in which abnormal breast cells grow and divide uncontrollably, resulting in the development of cancerous tissue. Detecting breast cancer at the preliminary phase is vital for improving survival rates and diagnostic outcomes. Though numerous Deep Learning (DL) frameworks have been proposed for detecting breast cancer, attaining accurate outcomes remains challenging. Thus, the Fuzzy-based Residual-ShuffleNet (Fuzzy RS-Net) is proposed for detecting breast cancer using mammogram images. Primarily, the mammogram image sourced from the dataset is fed as input to the wavelet domain filtering for noise reduction in the pre-processing stage. Further, the Object Segmentation Network (O-SegNet) is employed to segregate the affected region. Afterwards, image augmentation is effectuated using processes, such as rotation, shifting, and erasing. Further, feature extraction is processed, where texture features, Pyramid Histogram of Oriented Gradients (PHOG), and Weber Local Binary Pattern (WLBP) are extracted. At last, Fuzzy RS-Net is exploited for detecting breast cancer. In addition, the Fuzzy RS-Net is formulated by merging the Deep Residual Network (DRN), the Fuzzy concept, and ShuffleNet. Moreover, the developed Fuzzy RS-Net recorded the highest value of accuracy at 94.999%, sensitivity at 95.899%, and specificity at 93.889%.

Interface Passivation Inhibition Enabled by Anode–Cathode Synergistic Engineering for High‐Efficiency Electrodeposition of Transition Metals

ABSTRACT Room‐temperature electrodeposition is widely used to fabricate transition‐metal materials and alloys, but severe interfacial passivation drastically reduces current efficiency. More importantly, the intrinsic origin of interfacial passivation remains insufficiently understood, which has hampered the development of effective mitigation strategies. Herein, taking multivalent Ti as a representative example, we demonstrated that the bonding between Ti−Cl and the electrode downshifts the d‐band center of the electrode by 0.15 eV, markedly suppressing ion adsorption and charge transfer at the interface. Further operando studies showed that anodic dissolution generated [Ti(Al 2 Cl 7 ) 4 ] 2− with a unique coordination environment that prevented the bonding between Ti–Cl and the electrode, while offering a faster migration rate and lower desolvation energy. Building on these insights, anodic and cathodic potentials were co‐regulated to couple Ti (II) dissolution and deposition. Furthermore, an optimized pulsed electrolysis protocol was introduced to jointly regulate interfacial ion migration and reaction kinetics, consequently maintaining stable electrode potentials for Ti/Ti (II) redox. Enabled by this anode–cathode synergistic engineering, an unprecedented current efficiency 93% was achieved even at a high Ti content. This work provides electronic‐scale insight into the interfacial passivation during room‐temperature transition‐metal electrodeposition and offers a straightforward and implementable strategy for scalable manufacturing of transition‐metal materials and alloys.

Study on spontaneous combustion characteristics and fire prevention technology in the fully mechanized top-coal caving face of Gaojiapu coal mine

Abstract To address the issue of spontaneous combustion, the spontaneous combustion propensity of the coal body and the indicator gases of spontaneous combustion in the 3406 fully mechanized top-coal caving face were determined, and the oxygen concentration and the air leakage distribution across the working face were analyzed. The COMSOL was used to spontaneous combustion “Three Zones” were precisely divided. Based on these findings, a targeted fire prevention and control scheme for the goaf area was developed. The results show that: (1) The coal seam in the working face poses a risk of spontaneous combustion. Temperature-programmed oxidation experiments on coal samples identified CO and C 2 H 4 as the indicator gases for spontaneous combustion. (2) The asphyxiation zone is distributed in the deep goaf at 230–261 m from the working face; The oxidation zone in the return-side goaf at 12–230 m and in the intake-side goaf at 70–261 m; The heat dissipation zone lies in the goaf within 12–70 m. The maximum width of the oxidation zone is 218 m. (3) An integrated fire prevention and control technology combining “grouting and nitrogen injection” was implemented for the goaf area. The spontaneous combustion in the goaf area was prevented.

Correction to “Imaging‐Based High‐Content Screening With Clickable Probes Identifies XPB Inhibitors”

The effect of green carbon Dots/Titanium dioxide for photocatalytic reduction of CO2

Abstract With the rapid rate of industrial modernization, the continuous emissions of carbon dioxide (CO 2 ) are greatly disturbing the natural carbon balance and contributing to global warming. To mitigate this effect, photocatalytic reduction of carbon dioxide has gained popularity as a means of converting it into useful products. This study examined the photocatalytic reduction of aqueous CO 2 under ultraviolet irradiation (UV) using green carbon dots (CDs) made from pomegranate peel, nano titanium dioxide (TiO 2 ), TiO 2 /CDs composite, and metal-loaded carbon dots-modified titanium oxide (Cu-CDs/TiO 2 ). The reduction of CO 2 gas in water was carried out in a batch reactor utilizing the four photocatalysts. In order to verify the catalysts’ functional groups, nanoscale shape, and composite production, FTIR and TEM were used for characterization. The findings demonstrated that oxygenated products were preferred by pure CDs, but the performance of TiO 2 was very pH dependent, with ester formation being promoted in acidic environments and CO formation in alkaline ones. An increase in CO selectivity resulted from the TiO 2 -CDs composite’s enhanced charge separation and electron transfer; a change toward decreased hydrocarbons in product distribution was brought about by the addition of Cu, which opened hydrogenation pathways.

Designing Pyridinium‐Catalyzed Interfacial Polymerization for High‐Performance Acid‐Resistant Nanofiltration Membranes

ABSTRACT The “acyl ∼ amine” interfacial polymerization is widely studied to synthesize polyamide membranes, which, despite broad separation applications, suffer from poor acid stability. Cyanuric chloride (CC) can react with amines to form acid‐stable C─N bonds, yet its third chloride atom is unreactive at room temperature, thus hindering the synthesis of selective membranes by interfacial polymerization. This work reported a pyridinium‐catalyzed interfacial polymerization (PCIP) strategy to significantly improve CC's reactivity and synthesize high‐performance, acid‐resistant membranes. We designed a new monomer bearing triple pyridines, which were converted to positively charged pyridiniums during their interfacial polymerization with CC. These pyridiniums effectively reduce the electron density of CC rings via their electron‐withdrawing capacity, and improve CC's substitution reactivity by orders of magnitude, thereby enabling the rapid (1 min) synthesis of a large‐area (∼0.5 m 2 ) membrane. The membrane is stable in 2 M H 2 SO 4 , showing one of the highest separation performances (permeance: ∼16.8 L m −2 h −1 bar −1 ; selectivity: ∼12.8) among previous CC‐based membranes, combined with ∼4 times higher efficiency in lithium and cobalt recovery from LiCoO 2 spent batteries.

Dietary subnetwork strength differs by sex in opposite directions between sudden cardiac arrest cases and community controls

Baseline characterization of inshore reef soundscapes and noise dynamics along the southeast coast of South Africa

Separating predictive accuracy from functional behaviour in machine-learning surrogate models for geoengineering applications

Asymmetric Iron‐Catalyzed Vicinal C(sp ³ )─H Diamination of Carboxylic Acids

ABSTRACT The direct construction of chiral 1,2‐diamines through the stereoselective functionalization of two vicinal C(sp 3 )─H bonds remains a significant synthetic challenge. We report an iron‐catalyzed, carboxylate‐directed asymmetric vicinal α,β‐C(sp 3 ) ─H diamination of readily available carboxylic acids that furnishes chiral α,β‐diamino acids in a single pot with high regio‐, diastereo‐, and enantioselectivity (up to &gt;20:1 dr and &gt;99% ee). Using a chiral tetradentate N4‐ligated Fe(II) catalyst and BocNHOMs as the aminating reagent, a broad range of aromatic and aliphatic substrates undergo two sequential, nitrene‐mediated C─H aminations under mild conditions. Mechanistic studies indicate stepwise amination via iron−nitrenoid species, where the initial site of hydrogen‐atom transfer (β for aromatic substrates, α for aliphatic ones) dictates the order of functionalization. The method tolerates diverse functional groups and operates enantioconvergently for selected racemic substrates. This sustainable iron‐catalyzed strategy enables direct conversion of abundant carboxylic acids into versatile chiral α,β‐diamino building blocks amenable to peptide synthesis and heterocycle formation.

Subtype-specific differences in chromatin state markers and their morphometric predictors in breast cancer micronuclei

Abstract Micronuclei (MN) are indicators of chromosome instability and have been used for breast cancer (BC) screening, diagnosis, and prognosis. In this study, we explored the expression of transcription, replication, chromatin state, and DNA damage markers in BC MN using in vitro BC cell line (CL) models. Immunostaining using anti RNA Pol II, Lamin B1, emerin, H3K9ac, H3K27me3, cGAS, and γH2AX antibodies was performed, followed by confocal microscopy in MCF-7, T47D (hormone receptor+), SKBR3 (human epidermal growth factor receptor; HER2+), and MDA-MB-231 &amp; 468 triple negative (TN) BC CLs. Quantitative analysis showed that 85–90% of MN were Lamin B1+ in all subtypes, with a predominance of disrupted staining (80–85%), indicating compromised micronuclear envelope integrity. Euchromatin (H3K9ac) and heterochromatin (H3K27me3) markers were expressed in 60–70% and 20–30%, MN respectively demonstrating enrichment of transcriptionally permissive chromatin. RNA Pol II positivity was observed in 75–85% of MN, with TNBC cells exhibiting a significantly higher frequency (~85%) compared to non-TNBC subtypes (p&lt;0.001). Similarly, γ-H2AX and cGAS + MN were significantly more abundant in TNBC (55–60% and 40-45%) than in hormone receptor and HER2+ cells (45–50% and 32-35%) (γ-H2AX ; p&lt;0.0001 and cGAS ; p&lt;0.001). Logistic regression analysis revealed that MN morphometric and texture parameters, including area, fractal dimension, contrast, entropy, and angular second moment, significantly predicted RNA Pol II, Lamin B1, and γ-H2AX staining outcomes (p&lt;0.01). Our findings indicate an active role of BC MN in chromatin remodeling which can be detected using a set of advanced image analysis parameters used in study. Differences in the frequency of MN expressing above markers in TNBC and Non-TNBC cells indicate their crucial role in etiopathogenesis, which needs to be studied further.