Four undescribed coumarin derivatives, with ten amides from the roots of Ficus hirta and their cytotoxic activities.

Four undescribed coumarin derivatives, ficusalt A (1) and ficusalt B (2), a pair of racemic coumarins, (±) ficudimer A (3a/3b), along with ten known amides, were isolated from the roots of Ficus hirta. Their structures were elucidated by several spectroscopic data analyses, including HRESIMS, NMR, and X-ray single-crystal diffraction. The cytotoxic activities of all compounds against HeLa, HepG2, MCF-7, and H460 cell lines were detected using the MTT assay. Among these, 5 showed the highest activity against HeLa cells. Subsequently, the apoptotic, anti-invasive, and anti-migration effects of 5 on HeLa cells were determined by flow cytometer, transwell invasion assay, and wound-healing assay, respectively. The result suggested that 5 distinctly induced the apoptosis in HeLa cells and inhibited their invasion and migration. Further studies on anticancer mechanisms were conducted using Western blotting. As a result, 5 increased the cleavage of PARP and the expression of pro-apoptotic protein Bax. Moreover, 5 notably upregulated the phosphorylation of p38 and JNK, whereas inhibited the expression of p-ERK and p-AKT. Our results demonstrated that 5 could be a potential leading compound for further application in the treatment of cervical cancer.

Comprehensive Analysis on Prognostic Signature Based on T Cell-Mediated Tumor Killing Related Genes in Gastric Cancer.

Although immunotherapy is a valuable treatment for gastric cancer (GC), identifying the patients who would benefit most from this approach presents a challenge. In this study, GC patients were divided into two subtypes by consensus clustering according to T cell-mediated tumor killing related genes (TTKRGs), and there were significant differences in tumor-infiltrating immune cells, signaling pathways, and gene expression of immunomodulators and inhibitory immune checkpoints between the two subtypes. Then, we developed an individualized signature based on TTKRGs, and its clinical and predictive value in GC patients for chemotherapeutic and immunotherapeutic responses was assessed. We confirmed the expression levels of signature genes in GC tumor tissue using quantitative real-time polymerase chain reaction (qRT-PCR). Additionally, to improve the accuracy of GC prognosis predictions, we established a nomogram. We further identified some compounds as sensitive drugs targeting GC risk groups. The signature showed significant predictive ability across RNA-seq, microarray, and qRT-PCR cohorts, which could assist in predicting survival, immunotherapeutic and chemotherapeutic outcomes in GC patients.

Sub-high amylose maize starch: an ideal substrate to generate starch with lower digestibility by fermentation of Qu.

BACKGROUND: The fermentation of Qu (FQ) is a novel method to modify the properties of starch to expand its application and especially to increase the resistant starch (RS) content. Using waxy maize starch (WMS) as a fermentation substrate can increase the RS content significantly but it may be time consuming and not cost effective due to the almost negligible RS content of WMS. To solve this problem, we hypothesized that sub-high amylose starch (s-HAMS), with an amylose content close to 50% could be an ideal substrate for FQ. RESULTS: The results showed that FQ did not change the shape and the particle size of starch granules, the gelatinization peak (Tp), or the conclusion temperature (Tc), but the slowly digested starch content declined. Rapidly digested starch content fluctuated during FQ and the amylose content decreased within 36 h and then increased. Within 24h, FQ significanlty increased these values: the RS content, relative crystallinity (RC), the ratio of FTIR absorbances at 1047/1022cm-1, the diffraction peak at 19.8° in X-ray diffraction (XRD), and the gelatinization onset temperature (To) increased significantly, within 24 h of FQ. However, after 24 h of fermentation, the RS content, RC, the ratio of FTIR absorbances at 1047/1022 cm-1, and gelatinization enthalpy (ΔH) decreased significantly. CONCLUSION: Sub-high amylose starch is more suitable for FQ to produce low digestibility starch, and the increase in RS may be due to the formation of 'amylose-lipid' complexes (RS5). © 2024 Society of Chemical Industry.

Vimentin and tumor-stroma ratio for neoadjuvant chemoradiotherapy response prediction in locally advanced rectal cancer.

Vimentin expression in tumor tissues and the tumor-stroma ratio (TSR) have been demonstrated as strong prognostic factors for cancer patients, but whether they are predictive markers of neoadjuvant chemoradiotherapy (nCRT) outcome in locally advanced rectal cancer (LARC) patients is poorly understood. This study aimed to explore the predictive significance of vimentin and TSR combined for nCRT response in LARC patients. Imaging mass cytometry (IMC) was performed to determine the association of vimentin and TSR with nCRT response in six LARC patients [three achieved pathological complete response (pCR), three did not]. Immunohistochemistry (IHC) for vimentin and TSR on biopsy tissues before nCRT and logistic regression analysis were performed to further evaluate their predictive value for treatment responses in a larger patient cohort. A trend of decreased vimentin expression and increased TSR in the pCR group was revealed by IMC. In the validation group, vimentin [odds ratio (OR) 0.260, 95% confidence interval (CI) 0.102-0.602, p = 0.002] and TSR (OR 4.971, 95% CI 1.933-15.431, p = 0.002) were associated with pCR by univariate analysis. Patients in the vimentin-low/TSR-low or vimentin-high/TSR-high (OR 5.211, 95% CI 1.248-35.582, p = 0.042) and vimentin-low/TSR-high groups (OR 11.846, 95% CI 3.197-77.079, p = 0.001) had significantly higher odds of pCR. By multivariate analysis, only the combination of vimentin and TSR was an independent predictor for nCRT response (OR 9.324, 95% CI 2.290-63.623, p = 0.006). Our study suggested that the combined assessment of vimentin and TSR can provide additive significance and may be a promising indicator of nCRT response in LARC patients.

Controllable Crystallization of Two-Dimensional Bi Nanocrystals with Morphology-Boosted CO2 Electroreduction in Wide pH Environments.

Two-dimensional low-melting-point (LMP) metal nanocrystals are attracting increasing attention with broad and irreplaceable applications due to their unique surface and topological structures. However, the chemical synthesis, especially the fine control over the nucleation (reduction) and growth (crystallization), of such LMP metal nanocrystals remains elusive as limited by the challenges of low standard redox potential, low melting point, poor crystalline symmetry, etc. Here, a controllable reduction-melting-crystallization (RMC) protocol to synthesize free-standing and surfactant-free bismuth nanocrystals with tunable dimensions, morphologies, and surface structures is presented. Especially, ultrathin bismuth nanosheets with flat or jagged surfaces/edges can be prepared with high selectivity. The jagged bismuth nanosheets, with abundant surface steps and defects, exhibit boosted electrocatalytic CO2 reduction performances in acidic, neutral, and alkaline aqueous solutions, achieving the maximum selectivity of near unity at the current density of 210 mA cm-2 for formate evolution under ambient conditions. This work creates the RMC pathway for the synthesis of free-standing two-dimensional LMP metal nanomaterials and may find broader applicability in more interdisciplinary applications.

Low-Pressure Sensitive Piezochromic Fluorescence Switching of Tetraphenylethylene-Anthraquinone.

Invited for the cover of this issue are Prof. Wenjing Tian and co-workers at Jilin University. The image depicts the highly sensitive piezochromic fluorescence switching of tetraphenylethylene-anthraquinone under low-pressure regimes (∼60 kPa). Read the full text of the article at 10.1002/chem.202301070.

Low-Pressure Sensitive Piezochromic Fluorescence Switching of Tetraphenylethylene-Anthraquinone.

Sensing of low-pressure signals is of great importance for cutting-edge technologies. Organic piezochromic molecules offer a promising library of pressure sensitive materials which can be tailor-designed toward specific requirements. However, very few examples of low-pressure sensitive piezochromic fluorescent molecules have been obtained till date, and the underlying mechanisms are still in its infancy. Herein, we report highly sensitive piezochromic fluorescent switching under low-pressure regimes (∼60 kPa) of tetraphenylethylene-anthraquinone (TPE-AQ) based on the controlled molecular design and polymorphic phase strategy. The influence of both intramolecular conformation effect and variations of intermolecular stacking modes on the piezochromic property of TPE-AQ is investigated. The underlying mechanism of the low-pressure sensitive piezochromic fluorescence switching is demonstrated to be closely related to the loosely packed molecular orientation, as confirmed by X-ray diffraction measurements combined with simulations. This work provides a way to design highly efficient pressure sensors based on organic molecular systems.

Enhancement of Circularly Polarized Luminescence from Pulsating Nanotubules.

Enhancing the dissymmetry factor (glum ) is a crucial issue in developing circularly polarized luminescence (CPL) materials. Herein, based on supramolecular self-assembly of diethyl l-glutamate-cyanodiarylethene (L-GC) in mixed solution of EtOH-H2 O with different water fraction, enhanced circularly polarized emission from pulsating nanotubules is realized. In the mixture of ethanol and water (30/70, v/v), L-GC self-assembles into roll-up-type dense nanotubes and shows l-CPL. Remarkably, by increasing the water fraction to 80% and 90%, the diameter of the roll-up nanotubes increases and the dissymmetry factor of the nanotubes is significantly enhanced from 6.9 × 10-3  (dense nanotubes) to 3.7 × 10-2 (loose nanotubes) because of the enhanced intermolecular interactions and more ordered supramolecular stacking when increasing the water fraction. An efficient way is provided here to realize the increase of the dissymmetry factor by only changing the composition of solvents.

Apocarotenoids from Equisetum debile Roxb. ex Vaucher regulate the lipid metabolism via the activation of the AMPK/ACC/SREBP-1c signaling pathway.

Sixteen undescribed apocarotenoids (1-16), along with 22 known analogues, were isolated from the aerial parts of Equisetum debile. Their structures, including absolute configurations, were elucidated by NMR, HRESIMS, X-ray diffraction analysis, the modified Mosher's method and the quantum-chemical calculation of electronic circular dichroism (ECD) spectra. Compounds 1-9, 11-12 are the first example of C16-apocarotenoids appeared in nature. The plausible biosynthetic pathway of 1-16 was proposed. Moreover, the isolates were evaluated for their lipid-lowering activity, and the results showed that 13, 14, 15, 22, 31, 32 and 33 could remarkably decrease the levels of both TC and TG in FFA induced HepG2 cells at 20 µM. The oil red staining assay further demonstrated the lipid-lowering effects of 13, 14 and 15. The western blot results indicated that compounds 13, 14 and 15 could regulate the lipid metabolism via the activation of the AMPK/ACC/SREBP-1c signaling pathway. A preliminary structure-activity relationship (SAR) study of the isolates indicated that the apocarotenoids with 6/5 ring system displayed more potent lipid-lowering effects.

Joint Effects Between CDKN2B/P15 Methylation and Environmental Factors on the Susceptibility to Gastric Cancer.

BACKGROUND: The incidence of gastric cancer has long been at a high level in China, seriously affecting the health of Chinese people. AIMS: This case‒control study was performed to identify gene methylation biomarkers of gastric cancer susceptibility. METHODS: A total of 393 gastric cancer cases and 397 controls were included in this study. Gene methylation in peripheral blood leukocytes was detected by a methylation-sensitive high-resolution melting method, and the Helicobacter pylori antibody presence was semi-quantified in serum by ELISA. RESULTS: Individuals with total methylation of CDKN2B/P15 had a 1.883-fold (95%CI: 1.166-3.040, P = 0.010) risk of gastric cancer compared with unmethylated individuals. Individuals with both CDKN2B/P15 and NEUROG1 methylation had a higher risk of gastric cancer (OR = 2.147, 95% CI: 1.137-4.073, P = 0.019). The interaction between CDKN2B/P15 and NEUROG1 total methylation on gastric cancer risk was affected by the pattern of adjustment. In addition, the joint effects between CDKN2B/P15 total methylation and environmental factors, such as freshwater fish intake (OR = 6.403, 95% CI = 2.970-13.802, P < 0.001), irregular diet (OR = 5.186, 95% CI = 2.559-10.510, P < 0.001), unsanitary water intake (OR = 2.238, 95% CI = 1.144-4.378, P = 0.019), smoking (OR = 2.421, 95% CI = 1.456-4.026, P = 0.001), alcohol consumption(OR = 2.163, 95% CI = 1.309-3.576, P = 0.003), and garlic intake(OR = 0.373, 95% CI = 0.196-0.709, P = 0.003) on GC risk were observed, respectively. However, CDKN2B/P15 and NEUROG1 total methylation were not associated with gastric cancer prognosis. CONCLUSION: CDKN2B/P15 methylation in peripheral blood may be a potential biomarker for evaluating susceptibility to gastric cancer. The joint effects between CDKN2B/P15 methylation and environmental factors may also contribute to gastric cancer susceptibility.

Polymorphic Covalent Organic Frameworks: Molecularly Defined Pore Structures and Iodine Adsorption Property.

Radioactive iodine-capturing materials are urgently needed for the emerging challenges in nuclear waste disposal. The various pore structures of covalent organic frameworks (COFs) render them promising candidates for efficient iodine adsorption. However, the detailed structure-property relationship of COFs in iodine adsorption remains elusive. Herein, two polymorphic COFs with significantly different crystalline structures are obtained based on the same building blocks with varied molecular ratios. The two COFs both have high crystallinity, high specific surface area, and excellent chemical and thermal stability. Compared with the [C4+C4] topology (PyT-2) with an AA stacking form, the [C4+C2] topology (PyT-1) with an AB stacking form has more twisted pore channels and complex ink-bottle pores. At ambient conditions, PyT-1 and PyT-2 both exhibit good adsorption properties for iodine capture either in a gaseous or liquid medium. Remarkably, PyT-1 presents an excellent maximum adsorption capacity (0.635 g g-1), and the adsorption limit of PyT-2 is 0.445 g g-1 in an n-hexane solution with an iodine concentration of 400 mg L-1, which is highly comparable to the state-of-the-art iodine absorption performance. This study provides a guide for the future molecular design strategy toward novel iodine adsorbents.

Photoinduced Fluorescence Switching in Molecular Aggregates by Topological [2+2] Cycloaddition.

The optical modulation of fluorescence characteristics in molecular aggregates, which mainly involves diverse molecular stacking and the consequent intermolecular interactions, remains a significant challenge for potential applications in optical anticounterfeiting, data storage, and imaging. Here we successfully realize in situ fluorescence switching in molecular aggregates of thianaphthene-dioxide derivatives by topological [2+2] photocycloaddition, which represents a promising way to regulate the molecular stacking and alter photophysical processes. Notably, 2-(3,5-bis-trifluoromethylphenyl)benzo[b]thiophene-dioxide (BTO-TF) in both crystal and powder forms exhibits a unique switching from an initial nonfluorescent state to a highly fluorescent state (ΦPL =0.46) upon UV irradiation, because of the destruction of the [2+2] cycloaddition process by volume expansion of the photodimer. Furthermore, we demonstrate such a [2+2] photocycloaddition can occur when 2-(4-carboxypheny)benzo[b]thiophene-dioxide (BTO-OH) is doped within selective polymer matrixes, and can be utilized for the visualization of macrophase separation in polymer blends.

Risk and Prognosis of Second Primary Cancers among Ovarian Cancer Patients, Based on SEER Database.

The purposes of the present study were to elucidate the risk and prognostic effect of second primary cancers (SPCs) development, as well as the factors influencing the prognosis of OC patients with SPCs. A statistically significant increase in SPCs risk was observed among OC patients during 2004-2015. The independent factors were used to construct the SPCs-prediction nomogram and the OS-prediction nomogram. Both nomogram were subjected to internal validation and performed well. OC patients with SPCs have a better prognosis than patients without SPCs. Propensity score matching (PSM) was applied to reduce confounding.

An Oxidant- and Catalyst-Free Electrooxidative Cross-Coupling Approach to Synthesize meso-Substituted Porphyrin Derivatives.

The synthesis of porphyrin and chlorin derivatives has attracted significant attention due to their numerous applications. Herein, we report an environment friendly oxidant- and catalyst-free electrooxidative cross-coupling approach for multiple coupling reactions to synthesize meso C-N, C-O, and C-S substituted porphyrin and chlorin derivatives. For C-N cross-coupling reactions, diaminated porphyrins were obtained as the main products, while using 4-bromo-2,6-dimethyl aniline resulted in monoaminated product. Similarly, electrochemical catalysis of porphyrins with phenol and thiophene produced meso-disubstituted porphyrins in moderate yields under a smaller current. Chlorins were also applicable, and 20-substituted products were efficiently produced regioselectively. To the best of our knowledge, this work represents the first example of electrooxidative C-X cross-coupling of porphyrins and chlorins.

Discrete Platinum(II) Metallacycles with Inner- and Outer-Modified 9,10-Distyrylanthracene: Design, Self-Assembly, and Luminescence Properties.

To completely unravel the relationship between structures and luminescence properties of inner- and outer-modified metallacycles, two rhombic metallacycles S1 and S2 with 9,10-distyrylanthracene (DSA) were constructed herein via the design of DSA moieties on the inside or outside of metallacycles. Similar building blocks of the two metallacycles led to the same emission wavelengths in a dilute solution. In contrast, their fluorescence emissions in the aggregation and solid states were significantly different and revealed interesting emission behaviors from structures with inner- and outer-modified design. Finally, based on their luminescence properties, a tunable solid-state fluorescence emissive material was easily obtained by the mixing of two supramolecules in different ratios. This unique design suggested that the modified position of fluorophores exerts a key impact on the adjustment of luminescence from a dilute solution to the aggregated state and will be of great significance for the development of luminescent materials based on supramolecules.

Urchin-like PdOs nanostructure for hydrogen evolution electrocatalysis.

The compositional and structural engineering of advanced nanomaterials for hydrogen evolution reaction (HER) is highly necessary for efficient hydrogen production. Herein, PdOs nanospine assemblies (PdOs NAs) with urchin-like structures are fabricated via one-step route using DM-970 and KBr as surfactant agent and capping agent, respectively. Benefiting from electronic effect and multi-branched structure, the PdOs NAs exhibit superior performance for HER in alkaline and neutral solutions, requiring overpotentials of 28 and 35 mV at -10 mA cm-2, respectively, as well as superior long-term stability. This study offers a universal approach for the fabrication of active Pd-based catalysts with multi-branched morphology for efficient water electrolysis and beyond.

Risk factors associated with cardiovascular mortality among gastric cancer patients: a population-based analysis.

BACKGROUND: Cancer patients were found at a high risk of death from cardiovascular disease. This study aims to assess cardiovascular mortality risk and identify the potential risk factors associated with cardiovascular mortality among gastric cancer patients. METHODS: Gastric cancer patients were collected from the Surveillance Epidemiology and End Results database during 1975-2016. Standardized mortality ratios were calculated to compare cardiovascular mortality rates between gastric cancer patients and the general US population. Univariable Cox analysis and multivariable stepwise Cox analysis were adopted to identify the potential risk factors for cardiovascular disease death after gastric cancer diagnosis. RESULTS: There were 10 886 cardiovascular disease deaths identified among 165 433 individuals with gastric cancer observed for 410207.20 person-years. Gastric cancer patients were at a higher cardiovascular disease mortality risk (standardized mortality ratio = 3.35, 95% confidence interval: 3.24-3.47, P < 0.05). The study showed that older age at diagnosis (>80 years vs. 0-69 years, hazard ratio = 7.05, 95% confidence interval: 6.66-7.46, P < 0.001; 70-80 years vs. 0-69 years, hazard ratio = 3.35, 95% confidence interval: 3.19-3.53, P < 0.001), male sex (vs. female, hazard ratio = 1.39, 95% confidence interval: 1.33-1.45, P < 0.001), black race (vs. white, hazard ratio = 1.31, 95% confidence interval: 1.24-1.38, P < 0.001), without a partner (divorced/separated vs. married/partnered, hazard ratio = 1.35, 95% confidence interval: 1.25-1.45, P < 0.001; single vs. married/partnered, hazard ratio = 1.20, 95% confidence interval: 1.12-1.29, P < 0.001; widowed vs. married/partnered, hazard ratio = 1.41, 95% confidence interval: 1.34-1.48, P < 0.001), living in the northern plains (vs. pacific coast, hazard ratio = 1.23, 95% confidence interval: 1.16-1.29, P < 0.001) and surgery not performed (vs. performed, hazard ratio = 1.70, 95% confidence interval: 1.61-1.79, P < 0.001) were significantly associated with increased risk of cardiovascular disease death. Compared with patients with localized stage, distant staged patients were less likely to die of cardiovascular disease (hazard ratio = 0.88, 95% confidence interval: 0.83-0.94, P < 0.001). CONCLUSIONS: Gastric cancer patients were at an increased risk of cardiovascular disease death. Older age at diagnosis, male sex, black race, without a partner, living in the northern plains and surgery not performed were significantly associated with cardiovascular disease death after gastric cancer diagnosis.

Tautomeric phytosterols from Vernonia amygdalina Delile and their anti-cervical cancer activity.

Vernonia amygdalina Delile is generally used as green vegetables for cuisine in Nigeria and health tea or products in southeast of china. It was also used as folk medicine for the treatment of anti-helminth, febrifuge, digestive tonic and wounds. In this study, eleven undescribed phytosterols (1-2, 4-12) and six known analogues (3, 13-17) were isolated from the stems of V. amygdalina. Their structures including absolute configurations were elucidated by comprehensive spectroscopic methods (1D and 2D NMR, HRESIMS), X-ray diffraction and comparison of their ECD spectra. Besides, the tautomerism of phytosterols (1, 3-6, 12-17) with hemiacetal moiety were analyzed by solution NMR with different deuterated solvent and variable-temperature experiments. In addition, the cytotoxic activities of isolates against HeLa cells were evaluated. As a result, compound 10 exhibited the most potent anti-cervical cancer activity with the IC50 of 22.44 µM. Mechanism studies indicated that 10 triggered HeLa cells apoptosis through activating caspase signaling pathway. Furthermore, 10 could arrest the cell cycle in S phase and suppress the activation of the PI3K/AKT/mTOR pathway, leading to the inhibition of HeLa cells proliferation.

Seco-polyprenylated acylphloroglucinols from Hypericum elodeoides induced cell cycle arrest and apoptosis in MCF-7 cells via oxidative DNA damage.

Four undescribed seco-polyprenylated acylphloroglucinols (seco-PAPs), elodeoidesones A-D (1-4), were characterized from Hypericum elodeoides. Compound 1 represents the 1,6-seco-PAPs with fascinating 5/5 fused ring, while 2-4 possess a 1,2-seco-PAPs skeleton with a five-membered lactone core. Their structures including absolute configurations were established by spectroscopic analyses and quantum chemical computations. A possible biosynthetic pathway of 1-4 from normal PAPs was proposed. All the isolates were investigated for their cytotoxicity against tumor cells. Notably, 1 inhibited the proliferation of MCF-7 cells with the IC50 value of 7.34 µM. Mechanism investigation indicated that 1 induced MCF-7 cells apoptosis by blocking cell cycle at S phase via inducing oxidative DNA damage.

Deep-Red and Near-Infrared Iridium Complexes with Fine-Tuned Emission Colors by Adjusting Trifluoromethyl Substitution on Cyclometalated Ligands Combined with Matched Ancillary Ligands for Highly Efficient Phosphorescent Organic Light-Emitting Diodes.

Six novel Ir(C^N)2(L^X)-type heteroleptic iridium complexes with deep-red and near-infrared region (NIR)-emitting coverage were constructed through the cross matching of various cyclometalating (C^N) and ancillary (LX) ligands. Here, three novel C^N ligands were designed by introducing the electron-withdrawing group CF3 on the ortho (o-), meta (m-), and para (p-) positions of the phenyl ring in the 1-phenylisoquinoline (piq) group, which were combined with two electron-rich LX ligands (dipba and dipg), respectively, leading to subsequent iridium complexes with gradually changing emission colors from deep red (≈660 nm) to NIR (≈700 nm). Moreover, a series of phosphorescent organic light-emitting diodes (PhOLEDs) were fabricated by employing these phosphors as dopant emitters with two doping concentrations, 5% and 10%, respectively. They exhibited efficient electroluminescence (EL) with significantly high EQE values: >15.0% for deep red light0 (λmax = 664 nm) and >4.0% for NIR cases (λmax = 704 nm) at a high luminance level of 100 cd m-2. This work not only provides a promising approach for finely tuning the emission color of red phosphors via the easily accessible molecular design strategy, but also enables the establishment of an effective method for enriching phosphorescent-emitting molecules for practical applications, especially in the deep-red and near-infrared region (NIR).