Heteryunine A, an amidated tryptophan-catechin-spiroketal hybrid with antifibrotic activity from Heterosmilax yunnanensis.

An unprecedented spiro-C-glycoside adduct, heteryunine A (1), along with two uncommon alkaloids featuring a 2,3-diketopiperazine skeleton, heterpyrazines A (2) and B (3), were discovered in the roots of Heterosmilax yunnanensis. The detailed spectroscopic analysis helped to clarify the planar structures of these compounds. Compound 1, containing 7 chiral centers, features a catechin fused with a spiroketal and connects with a tryptophan derivative by a CC bond. Its complex absolute configuration was elucidated by rotating frame overhauser enhancement spectroscopy (ROESY), specific rotation, and the 13C nuclear magnetic resonance (NMR) and electronic circular dichroism (ECD) calculation. The possible biosynthetic routes for 1 were deduced. Compounds 1 and 2 showed significant antifibrotic effects and further research revealed that they inhibited the activation, migration and proliferation of hepatic stellate cells (HSCs) through suppressing the activity of Ras homolog family member A (RhoA).

X-ray Opaque Polymer Drug-Eluting Beads Loaded with Iodized Oil: Preparation and In Vitro and In Vivo Evaluations.

Drug-eluting microspheres are commonly used as a local drug delivery system for interventional therapy. However, current drug-eluting microspheres have poor X-ray visibility, which can hinder tracking and postembolization evaluation. In the current study, X-ray-visible poly(acrylic acid) drug-eluting beads loaded with iodized oil (IO-PAA-DEBs) ranging from 100-300 µm were prepared and evaluated both in vitro and in vivo. Iodized oil served as the radiopaque agent, and X-ray and computed tomography scanning confirmed that the microspheres exhibited excellent X-ray-visible properties. The drug-loading capacities of bleomycin hydrochloride, doxorubicin hydrochloride, and oxaliplatin were also investigated. IO-PAA-DEBs exhibited sustained drug release properties, accompanied by a cumulative drug release rate that reached approximately 60% after 120 h. In vitro and in vivo experiments revealed that IO-PAA-DEBs had good biocompatibility. Collectively, these results demonstrated that IO-PAA-DEBs could facilitate transarterial embolization and sustained drug delivery.

Phonon-Mediated Exciton Relaxation in Two-Dimensional Semiconductors: Selection Rules and Relaxation Pathways.

Exciton-phonon coupling (ExPC) is crucial for energy relaxation in semiconductors, yet the first-principles calculation of such coupling remains challenging, especially for two-dimensional (2D) systems. Here, an accurate method for calculating ExPC is developed and applied in exciton relaxation problems in monolayer WSe2. Considering the interplay between the exciton wave functions and electron-phonon coupling (EPC) matrix elements, we find that ExPC shows selection rules distinct from the ones of EPC. By employing the Wannier exciton model, we generalize these selection rules, which state that the angular quantum numbers of the exciton must match the winding numbers of the EPC matrix elements for the ExPC to be allowed. To verify our theory and method, we calculate intervalley exciton relaxation pathways, which agree well with a recent experiment.

The effect of hyperlipidemia on overall survival in patients with cancer was differentiated by BMI and hyperlipidemia type.

BACKGROUND AND AIMS: The impact of lipids on the overall survival (OS) of patients with malignancy has not yet been clarified. This study aimed to evaluate the effect of hyperlipidemia on the OS among Chinese patients based on Body Mass Index (BMI) stratifications and hyperlipidemia types. METHOD: The patients in this study were derived from the Investigation of the Nutrition Status and Clinical Outcome of Common Cancers (INSCOC) trial. Kaplan-Meier was used to draw the survival curve, and the log-rank test was used to estimate the survival rates between each group. Cox proportional hazards regression models were used to estimate the hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: A total of 9054 patients were included in the final study, with a median age of 59 years, and 55.3% (5004) of them were males. Regarding types of hyperlipidemia, only low high-density lipoprotein was an independent risk factor for the prognosis of all patients (HR = 1.35, 95% CI: 1.25-1.45, P < 0.001), while high total cholesterol (HR = 1.01, 95% CI: 0.90-1.15, P = 0.839) and high low-density lipoprotein (HR = 1.03, 95%CI: 0.91-1.16, P = 0.680) were not. In terms of BMI stratification, the effect of triglycerides on prognosis varied; high triglycerides were an independent risk factor for the prognosis of underweight patients (HR = 1.56, 95% CI:1.05-2.32, P = 0.027) and a protective factor for overweight patients (HR = 0.75, 95% CI: 0.63-0.89, P = 0.001). However, for normal-weight patients, there was no significant statistical difference (HR = 0.88, 95%CI: 0.75-1.03, P = 0.108). CONCLUSIONS: The impact of hyperlipidemia on the OS among patients with cancer varied by different BMI and hyperlipidemia types. BMI and hyperlipidemia type ought to be considered in combination to estimate the prognosis of patients with malignancy.

Hemolysis attributed to high dose vitamin C: Two case reports.

BACKGROUND: High-dose vitamin C treatment (HVCT) can reduce the adverse effect of chemotherapy and enhance the effect of antitumor therapy, which has been considered one of the safest alternative treatments. However, the severity of its adverse effects may have been underestimated. The most serious adverse effect is hemolysis, which may result in acute kidney injury or death. Although glucose-6-phosphate dehydrogenase (G6PD) deficiency is considered to be the main cause, the probability and pathological mechanism are not completely understood, leading to a lack of effective and standardized treatment methods. CASE SUMMARY: Two patients with colorectal cancer developed hemolytic anemia after using 1 g/kg HVCT. In contrast to previous cases, the lowest hemoglobin level in the two cases was < 50 g/L, which was lower than previously reported. This may be because Case 1 had chronic hepatitis B for many years, which caused abnormal liver reserve function, and Case 2 had grade II bone marrow suppression. Both patients improved and were discharged after blood replacement therapy. Our cases had the most severe degree of hemolysis but the best prognosis, suggesting that our treatment may be helpful for rescue of drug-induced hemolysis. This is the first review of the literature on hemolysis caused by HVCT, and we found that all patients with G6PD deficiency developed hemolysis after HVCT. CONCLUSION: G6PD deficiency should be considered as a contraindication to HVCT, and it is not recommended for patients with bone marrow suppression, moderate-to-severe anemia, hematopoietic abnormalities, or abnormal liver and kidney function. Early blood purification and steroid therapy may avoid acute kidney injury or death caused by HVCT-related hemolytic anemia.

Polarization-driven band topology evolution in twisted MoTe2 and WSe2.

Motivated by recent experimental observations of opposite Chern numbers in R-type twisted MoTe2 and WSe2 homobilayers, we perform large-scale density-functional-theory calculations with machine learning force fields to investigate moiré band topology across a range of twist angles in both materials. We find that the Chern numbers of the moiré frontier bands change sign as a function of twist angle, and this change is driven by the competition between moiré ferroelectricity and piezoelectricity. Our large-scale calculations, enabled by machine learning methods, reveal crucial insights into interactions across different scales in twisted bilayer systems. The interplay between atomic-level relaxation effects and moiré-scale electrostatic potential variation opens new avenues for the design of intertwined topological and correlated states, including the possibility of mimicking higher Landau level physics in the absence of magnetic field.

[Evaluation of chemical constituents of Draconis Sanguis and its protective effect on renal tubular injury in diabetic kidney disease].

The chemical constituents of Draconis Sanguis were preliminarily studied by macroporous resin, silica gel, dextran gel, and high-performance liquid chromatography. One retro-dihydrochalcone, four flavonoids, and one stilbene were isolated. Their chemical structures were identified as 4-hydroxy-2,6-dimethoxy-3-methyldihydrochalcone(1), 4'-hydroxy-5,7-dimethoxy-8-methylflavan(2), 7-hydroxy-4',5-dimethoxyflavan(3),(2S)-7-hydroxy-5-methoxy-6-methylflavan(4),(2S)-7-hydroxy-5-methoxyflavan(5), and pterostilbene(6) by modern spectroscopy, physicochemical properties, and literature comparison. Compound 1 was a new compound. Compounds 2 and 6 were first found in the Arecaceae family. Compound 5 had the potential to prevent and treat diabetic kidney disease.

Gate-Tunable Antiferromagnetic Chern Insulator in Twisted Bilayer Transition Metal Dichalcogenides.

A series of recent experimental works on twisted MoTe_{2} homobilayers have unveiled an abundance of exotic states in this system. Valley-polarized quantum anomalous Hall states have been identified at hole doping of ν=-1, and the fractional quantum anomalous Hall effect is observed at ν=-2/3 and ν=-3/5. In this Letter, we investigate the electronic properties of AA-stacked twisted bilayer MoTe_{2} at ν=-2 by k-space Hartree-Fock calculations. We identify a series of phases, among which a noteworthy phase is the antiferromagnetic Chern insulator, stabilized by an external electric field. We attribute the existence of this Chern insulator to an antiferromagnetic instability at a topological phase transition between the quantum spin hall phase and a band insulator phase. Our research proposes the potential of realizing a Chern insulator beyond ν=-1, and contributes fresh perspectives on the interplay between band topology and electron-electron correlations in moiré superlattices.

Supramolecular Chemotherapy: Complexation by Carboxylated Pillar[6]arene for Decreasing Cytotoxicity of Nitrogen Mustard to Normal Cells and Enhancing Its Antitumor Efficiency against Breast Cancer.

Advances in chemotherapeutic strategies are urgently required to improve antitumor efficiency. Herein, a carboxylated pillar[6]arene (CP6A) was employed to load chemotherapy medication, nitrogen mustard (NM), via forming a direct host-guest complex, as this helps to decrease the cytotoxicity of NM on normal mammary epithelial cells. Attributed to the stronger complexation ability of CP6A for endogenous spermine (SPM) than for NM, the complexed NM could be competitively released from the CP6A cavity via replacement with SPM. This chemotherapy strategy performed well in vitro and in vivo for SPM-overexpressed cancers. In comparison with free NM, antitumor efficiency of NM/CP6A was significantly enhanced, which originated from the synergistic effect of competitive release of NM and simultaneous trapping of SPM. This strategy might guide expansion to other first-line antitumor agents to improve therapeutic efficacy and decrease side effects, thereby replenishing the possibilities of supramolecular chemotherapy.

Relationship between educational level and survival of patients with cancer: A multicentre cohort study.

BACKGROUND: Although socioeconomic factors are important determinants of population mortality, the effect of educational level on the survival of patients with cancer in China is unclear. This study aimed to assess whether educational level is associated with the prognosis of patients with cancer and to explore the mediators of this association. METHODS: This multicentre cohort study included 18,251 patients diagnosed with cancer between May 2013 and December 2018. The main parameters measured were overall survival (OS) and all-cause mortality. The relationship between educational level and all-cause mortality was assessed using multifactor-corrected Cox survival analysis. Logistic regression was used to analyze the association between educational level and patient-generated subjective global assessment (PG-SGA). RESULTS: The mean age of the 18,251 participants (men, 9939 [54.4%]) was 57.37 ± 11.66 years. Multifactorial survival analysis showed that patients survived longer with increasing education (university and above vs. elementary school and below; p = p = <0.001, HR = 0.84, 95% CI: 0.77-0.92), and the differences were statistically significant in different subgroups. The potential impact factors included sex, age, TNM stage, and PG-SGA score. Logistic regression showed a significant negative association between educational level and the modifiable factor PG-SGA (secondary vs. primary and below; p = 0.004, HR = 0.90, 95% CI: 0.83-0.97; university and above vs. primary and below; p < 0.001, HR = 0.79, 95% CI: 0.71-0.88). CONCLUSIONS: Educational level was a significant prognostic factor for patients with cancer, independent of other known prognostic factors. This association was further improved by modifying the nutritional status.

Fractional Chern Insulator in Twisted Bilayer MoTe_{2}.

A recent experiment has reported the first observation of a zero-field fractional Chern insulator (FCI) phase in twisted bilayer MoTe_{2} moiré superlattices [J. Cai et al., Signatures of fractional quantum anomalous Hall states in twisted MoTe_{2}, Nature (London) 622, 63 (2023).NATUAS0028-083610.1038/s41586-023-06289-w]. The experimental observation is at an unexpected large twist angle 3.7° and calls for a better understanding of the FCI in real materials. In this Letter, we perform large-scale density functional theory calculation for the twisted bilayer MoTe_{2} and find that lattice reconstruction is crucial for the appearance of an isolated flat Chern band. The existence of the FCI state at ν=-2/3 is confirmed by exact diagonalization. We establish phase diagrams with respect to the twist angle and electron interaction, which reveal an optimal twist angle of 3.5° for the observation of FCI. We further demonstrate that an external electric field can destroy the FCI state by changing band geometry and show evidence of the ν=-3/5 FCI state in this system. Our research highlights the importance of accurate single-particle band structure in the quest for strong correlated electronic states and provides insights into engineering fractional Chern insulator in moiré superlattices.

Fourteen new 2-benzylbenzofuran glycosides with cardioprotective activity from Heterosmilax yunnanensis.

Fourteen new 2-benzylbenzofuran O-glycosides (1-13, 15) and one new key precursor, diarylacetone (14) were isolated from the roots of Heterosmilax yunnanensis Gagnep, which all have characteristic 2,3,4-O-trisubstituted benzyl. Their structures were elucidated by 1D and 2D NMR, HRESIMS, UV and IR. The isolated compounds were assessed for their cardioprotective activities and compounds 1, 3 and 6 could significantly improve cardiomyocytes viability. Moreover, the mechanistic study revealed that these three compounds could significantly decrease intracellular ROS levels and maintain mitochondrial homeostasis upon hypoxia inducement. Consequently, 1, 3 and 6 might serve as potential lead compounds to prevent myocardial ischemia.

MdbHLH162 connects the gibberellin and jasmonic acid signals to regulate anthocyanin biosynthesis in apple.

Anthocyanins are secondary metabolites induced by environmental stimuli and developmental signals. The positive regulators of anthocyanin biosynthesis have been reported, whereas the anthocyanin repressors have been neglected. Although the signal transduction pathways of gibberellin (GA) and jasmonic acid (JA) and their regulation of anthocyanin biosynthesis have been investigated, the cross-talk between GA and JA and the antagonistic mechanism of regulating anthocyanin biosynthesis remain to be investigated. In this study, we identified the anthocyanin repressor MdbHLH162 in apple and revealed its molecular mechanism of regulating anthocyanin biosynthesis by integrating the GA and JA signals. MdbHLH162 exerted passive repression by interacting with MdbHLH3 and MdbHLH33, which are two recognized positive regulators of anthocyanin biosynthesis. MdbHLH162 negatively regulated anthocyanin biosynthesis by disrupting the formation of the anthocyanin-activated MdMYB1-MdbHLH3/33 complexes and weakening transcriptional activation of the anthocyanin biosynthetic genes MdDFR and MdUF3GT by MdbHLH3 and MdbHLH33. The GA repressor MdRGL2a antagonized MdbHLH162-mediated inhibition of anthocyanins by sequestering MdbHLH162 from the MdbHLH162-MdbHLH3/33 complex. The JA repressors MdJAZ1 and MdJAZ2 interfered with the antagonistic regulation of MdbHLH162 by MdRGL2a by titrating the formation of the MdRGL2a-MdbHLH162 complex. Our findings reveal that MdbHLH162 integrates the GA and JA signals to negatively regulate anthocyanin biosynthesis. This study provides new information for discovering more anthocyanin biosynthesis repressors and explores the cross-talk between hormone signals.

Systemic inflammation and insulin resistance-related indicator predicts poor outcome in patients with cancer cachexia.

BACKGROUND: The C-reactive protein (CRP)-triglyceride-glucose (TyG) index (CTI), which is a measure representing the level of inflammation and insulin resistance (IR), is related to poor cancer prognosis; however, the CTI has not been validated in patients with cancer cachexia. Thus, this study aimed to explore the potential clinical value of the CTI in patients with cancer cachexia. METHODS: In this study, our prospective multicenter cohort included 1411 patients with cancer cachexia (mean age 59.45 ± 11.38, 63.3% male), which was a combined analysis of multiple cancer types. We randomly selected 30% of the patients for the internal test cohort (mean age 58.90 ± 11.22% 61.4% male). Additionally, we included 307 patients with cancer cachexia in the external validation cohort (mean age 61.16 ± 11, 58.5% male). Receiver operating characteristic (ROC) and calibration curves were performed to investigate the prognostic value of CTI. The prognostic value of the CTI was also investigated performing univariate and multivariate survival analyses. RESULTS: The survival curve indicated that the CTI showed a significant prognostic value in the total, internal, and external validation cohorts. Prognostic ROC curves and calibration curves revealed that the CTI showed good consistency in predicting the survival of patients with cancer cachexia. Multivariate survival analysis showed that an elevated CTI increased the risk of death by 22% (total cohort, 95% confidence interval [CI] = 1.13-1.33), 34% (internal test cohort, 95%CI = 1.11-1.62), and 35% (external validation cohort, 95%CI = 1.14-1.59) for each increase in the standard deviation of CTI. High CTI reliably predicted shorter survival (total cohort, hazard ratio [HR] = 1.45, 95%CI = 1.22-1.71; internal test cohort, HR = 1.62, 95%CI = 1.12-2.36; external validation cohort, HR = 1.61, 95%CI = 1.15-2.26). High CTI significantly predicted shorter survival in different tumor subgroups, such as esophageal [HR = 2.11, 95%CI = 1.05-4.21] and colorectal cancer [HR = 2.29, 95%CI = 1.42-3.71]. The mediating effects analysis found that the mediating proportions of PGSGA, ECOG PS, and EORTC QLQ-C30 on the direct effects of CTI were 21.72%, 19.63%, and 11.61%, respectively We found that there was a significant positive correlation between the CTI and 90-day [HR = 2.48, 95%CI = 1.52-4.14] and 180-day mortality [HR = 1.77,95%CI = 1.24-2.55] in patients with cancer cachexia. CONCLUSION: The CTI can predict the short- and long-term survival of patients with cancer cachexia and provide a useful prognostic tool for clinical practice.