Isoflurane preconditioning attenuates OGD/R-induced cardiomyocyte cytotoxicity by regulating the miR-210/BNIP3 axis.

Isoflurane, a commonly used inhaled anesthetic, has been found to have a cardioprotective effect. However, the precise mechanisms have not been fully elucidated. Here, we found that isoflurane preconditioning enhanced OGD/R-induced upregulation of miR-210, a hypoxia-responsive miRNA, in AC16 human myocardial cells. To further test the roles of miR-210 in regulating the effects of isoflurane preconditioning on OGD/R-induced cardiomyocyte injury, AC16 cells were transfected with anti-miR-210 or control anti-miRNA. Results showed that isoflurane preconditioning attenuated OGD/R-induced cardiomyocyte cytotoxicity (as assessed by cell viability, LDH and CK-MB levels), which could be reversed by anti-miR-210. Isoflurane preconditioning also prevented OGD/R-induced increase in apoptotic rate, caspase-3 and caspase-9 activities, and Bax level and decrease in Bcl-2 expression level, while anti-miR-210 blocked these effects. We also found that anti-miR-210 prevented the inhibitory effects of isoflurane preconditioning on OGD/R-induced decrease in adenosine triphosphate content; mitochondrial volume; citrate synthase activity; complex I, II, and IV activities; and p-DRP1 and MFN2 expression. Besides, the expression of BNIP3, a reported direct target of miR-210, was significantly decreased under hypoxia condition and could be regulated by isoflurane preconditioning. In addition, BNIP3 knockdown attenuated the effects of miR-210 silencing on the cytoprotection of isoflurane preconditioning. These findings suggested that isoflurane preconditioning exerted protective effects against OGD/R-induced cardiac cytotoxicity by regulating the miR-210/BNIP3 axis.

YTHDF2 favors protumoral macrophage polarization and implies poor survival outcomes in triple negative breast cancer.

Patients with triple-negative breast cancer (TNBC) frequently experience resistance to chemotherapy, leading to recurrence. The approach of optimizing anti-tumoral immunological effect is promising in overcoming such resistance, given the heterogeneity and lack of biomarkers in TNBC. In this study, we focused on YTHDF2, an N6-methyladenosine (m6A) RNA-reader protein, in macrophages, one of the most abundant intra-tumoral immune cells. Using single-cell sequencing and ex vivo experiments, we discovered that YTHDF2 significantly promotes pro-tumoral phenotype polarization of macrophages and is closely associated with down-regulated antigen-presentation signaling to other immune cells in TNBC. The in vitro deprivation of YTHDF2 favors anti-tumoral effect. Expressions of multiple transcription factors, especially SPI1, were consistently observed in YTHDF2-high macrophages, providing potential therapeutic targets for new strategies. In conclusion, YTHDF2 in macrophages appears to promote pro-tumoral effects while suppressing immune activity, indicating the treatment targeting YTHDF2 or its transcription factors could be a promising strategy for chemoresistant TNBC.

Giant Flexoelectricity in Bent Semiconductor Thinfilm.

We elucidate the flexoelectricity of semiconductors in the high strain gradient regime, the underlying mechanism of which is less understood. By using the generalized Bloch theorem, we uncover a strong flexoelectric-like effect in bent thinfilms of Si and Ge due to a high-strain-gradient-induced band gap closure. We show that an unusual type-II band alignment is formed between the compressed and elongated sides of the bent film. Therefore, upon the band gap closure, electrons transfer from the compressed side to the elongated side to reach the thermodynamic equilibrium, leading to a pronounced change of polarization along the film thickness dimension. The obtained transverse flexoelectric coefficients are unexpectedly high with a quadratic dependence on the film thickness. This new mechanism is extendable to other semiconductor materials with moderate energy gaps. Our findings have important implications for the future applications of flexoelectricity in semiconductor materials.

Machine-learning radiomics to predict bone marrow metastasis of neuroblastoma using magnetic resonance imaging.

Background: Neuroblastoma is one common pediatric malignancy notorious for high temporal and spatial heterogeneities. More than half of its patients develop distant metastases involving vascularized organs, especially the bone marrow. It is thus necessary to have an economical, noninvasive method without much radiation for follow-ups. Radiomics has been used in many cancers to assist accurate diagnosis but not yet in bone marrow metastasis in neuroblastoma. Methods: A total of 182 patients with neuroblastoma were retrospectively collected and randomly divided into the training and validation sets. Five-hundred and seventy-two radiomics features were extracted from magnetic resonance imaging, among which 41 significant ones were selected via T-test for model development. We attempted 13 machine-learning algorithms and eventually chose three best-performed models. The integrative performance evaluations are based on the area under the curves (AUCs), calibration curves, risk deciles plots, and other indexes. Results: Extreme gradient boosting, random forest (RF), and adaptive boosting were the top three to predict bone marrow metastases in neuroblastoma while RF was the most accurate one. Its AUC was 0.90 (0.86-0.93), F1 score was 0.82, sensitivity was 0.76, and negative predictive value was 0.79 in the training set. The values were 0.82 (0.71-0.93), 0.80, 0.75, and 0.92 in the validation set, respectively. Conclusions: Radiomics models are likely to contribute more to metastatic diagnoses and the formulation of personalized healthcare strategies in clinics. It has great potential of being a revolutionary method to replace traditional interventions in the future.

Safety and Survival Outcomes of Liver Resection following Triple Combination Conversion Therapy for Initially Unresectable Hepatocellular Carcinoma.

Triple combination conversion therapy, involving transcatheter arterial chemoembolization (TACE) or hepatic arterial infusion chemotherapy (HAIC) combined with tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs), has shown an encouraging objective response rate (ORR) and successful conversion surgery rate in initially unresectable hepatocellular carcinoma (HCC). However, the safety and long-term survival outcomes of subsequent liver resection after successful conversion still remain to be validated. From February 2019 to February 2023, 726 patients were enrolled in this retrospective study (75 patients received hepatectomy after conversion therapy [CLR group], and 651 patients underwent pure hepatectomy [LR group]). Propensity score matching (PSM) was used to balance the preoperative baseline characteristics. After PSM, 68 patients in the CLR group and 124 patients in the LR group were analyzed, and all the matching variables were well-balanced. Compared with the LR group, the CLR group experienced longer Pringle maneuver time, longer operation time, and longer hospital stays. In addition, the CLR group had significantly higher incidence rates of intra-abdominal bleeding, biliary leakage, post-hepatectomy liver failure (PHLF), and Clavien-Dindo grade IIIa complications than the LR group. There were no significant statistical differences in overall survival (OS) (hazard ratio [HR] 0.724; 95% confidence interval [CI] 0.356-1.474; p = 0.374) and recurrence-free survival (RFS) (HR 1.249; 95% CI 0.807-1.934; p = 0.374) between the two groups. Liver resection following triple combination conversion therapy in initially unresectable HCC may achieve favorable survival outcomes with manageable safety profiles; presenting as a promising treatment option for initially unresectable HCC.

Liquid Chromatography-Tandem Mass Spectrometry-Based Metabolomics Analysis of Indigo Naturalis Treatment of Ulcerative Colitis in Mice.

Ulcerative colitis (UC), often known as UC, is an inflammatory disease of the intestines that has frequent and long-lasting flare-ups. It is unknown precisely how the traditional Chinese drug Indigo Naturalis (IN) heals inflammatory bowel disease, despite its long-standing use in China and Japan. Finding new metabolite biomarkers linked to UC could improve our understanding of the disease, speed up the diagnostic process, and provide insight into how certain drugs work to treat the condition. Our work is designed to use a metabolomic method to analyze potential alterations in endogenous substances and their impact on metabolic pathways in a mouse model of UC. To determine which biomarkers and metabolisms are more frequently connected with IN's effects on UC, liquid chromatography-tandem mass spectrometry analysis of the serum metabolomics of UC mice and normal mice was performed. The outcomes demonstrated that IN boosted the health of UC mice and reduced the severity of their metabolic dysfunction. In the UC model, it was also found that IN changed the way 17 biomarkers and 3 metabolisms functioned.

Morphological Awareness and DHH Students' Reading-Related Abilities: A Meta-Analysis of Correlations.

This article presents the first meta-analysis on correlations of morphological awareness (MA) with reading-related abilities in deaf and hard-of-hearing (DHH) students (k = 14, N = 556). The results showed high mean correlations of MA with all three reading-related abilities: rs = 0.610, 0.712, and 0.669 (all ps < 0.001), respectively, for word reading, vocabulary knowledge, and reading comprehension. A set of moderator analysis was conducted of language, DHH students' age/reading stage and degree of hearing loss, and task type. The correlation of MA with word reading was significantly stronger in alphabetic than in non-alphabetic languages, and for fluency than accuracy; for vocabulary knowledge, the correlation was significantly stronger for production MA tasks than for judgment tasks; for reading comprehension, derivational MA tasks showed a stronger correlation than those having a mixed focus on inflection and derivation. While no other moderator effects were significant, the correlations for subsets of effect sizes were largely high for a moderator. These findings reaffirmed the importance of morphology in DHH students' reading development. The present synthesis, while evidencing major development of research on the metalinguistic underpinnings of reading in DHH students, also showed that the literature on MA is still very limited.

Aconicumines A-D, an advanced class of norditerpenoid alkaloids with an unprecedented N,O-diacetal motif from Aconitum taipeicum Hand.-Mazz., exhibit anti-inflammatory properties in vitro.

Aconicumines A-D, an advanced class of norditerpenoid alkaloids, and seven known alkaloids, were isolated from Aconitum taipaicum Hand.-Mazz. (Ranunculaceae). The structures of the previously undescribed compounds, including their absolute configurations, were fully elucidated based on spectroscopic and single-crystal X-ray diffraction data analysis. Aconicumines A-D exhibit interesting cage-like structure, characterised by an unprecedented N,O-diacetal moiety (C6-O-C19-N-C17-O-C7) that has not been previously observed in diterpenoid alkaloids. Possible biosynthetic pathways for aconicumines A-D were proposed. Aconitine, hypaconitine, and aconicumine A showed significant inhibition of nitric oxide production in RAW 264.7 macrophages induced by lipopolysaccharide with IC50 values ranging from 4.1 to 19.7 µM compared to positive control (dexamethasone, IC50 = 12.5 µM). Furthermore, the primary structure-activity relationships for aconicumines A-D were also represented.

Electric Field-Controlled Damping Switches of Coupled Dirac Plasmons.

For quasiparticle systems, the control of the quasiparticle lifetime is an important goal, determining whether the related fascinating physics can be revealed in fundamental research and utilized in practical applications. Here, we use double-layer graphene with a boron nitride spacer as a model system to demonstrate that the lifetime of coupled Dirac plasmons can be remotely tuned by electric field-controlled damping pathways. Essentially, one of the graphene layers serves as an external damping amplifier whose efficiency can be controlled by the corresponding doping level. Through this damping switch, the damping rate of the plasmon can be actively tuned up to 1.7 fold. This Letter provides a prototype design to actively control the lifetime of graphene plasmons and also broadens our horizon for the damping control of other quasiparticle systems.

Structurally diverse indole alkaloids from the leaves of Winchia calophylla.

Three unprecedented indole alkaloids, wincalines A-C (1-3), and four known ones (4-7), classified into six carbon skeletal types, were isolated from the leavesof Winchia calophylla. The new isolates including their absolute configurations were elucidated based on extensive spectroscopic methods, the X-ray diffraction analyses, and electronic circular dichroism (ECD) experiments, as well as comparison with literature data. Wincaline A (1) is a rare indole alkaloid zwitterion bearing a 5,5-spirocyclic moiety. A possible biosynthetic pathway for 1 was proposed. All compounds were evaluated for their anti-inflammatory effects in terms of nitric oxide (NO) production in RAW 264.7 cells stimulated by lipopolysaccharide (LPS). Nevertheless, compound 7 showed weak activity with 43% NO production inhibition rate at 100 µM.

Mixed-Valence CsCu4Se3: Large Phonon Anharmonicity Driven by the Hierarchy of the Rigid [(Cu+)4(Se2-)2](Se-) Double Anti-CaF2 Layer and the Soft Cs+ Sublattice.

Crystalline solids that exhibit inherently low lattice thermal conductivity (κlat) have attracted a great deal of attention because they offer the only independent control for pursuing a high thermoelectric figure of merit (ZT). Herein, we report the successful preparation of CsCu4Q3 (Q = S (compound 1), Se (compound 2)) with the aid of a safe and facile boron-chalcogen method. The single-crystal diffraction data confirm the P4/mmm hierarchical structures built up by the mixed-valence [(Cu+)4(Q2-)2](Q-) double anti-CaF2 layer and the NaCl-type Cs+ sublattice involving multiple bonding interactions. The electron-poor compound CsCu4Q3 features Cu-Q antibonding states around EF that facilitates a high σ value of 3100 S/cm in 2 at 323 K. Significantly, the ultralow κlat value of 2, 0.20 W/m/K at 650 K (70% lower than that of Cu2Se), is mainly driven by the vibrational coupling of the rigid double anti-CaF2 layer and the soft NaCl-type sublattice. The hierarchical structure increases the bond multiplicity, which eventually leads to a large phonon anharmonicity, as evidenced by the effective scattering of the low-lying optical phonons to the heat-carrying acoustic phonons. Consequently, the acoustic phonon frequency in 2 drops sharply from 118 cm-1 (of Cu2Se) to 48 cm-1. In addition, the elastic properties indicate that the hierarchical structure largely inhibits the transverse phonon modes, leading to a sound velocity (1571 m/s) and a Debye temperature (189 K) lower than those of Cu2Se (2320 m/s; 292 K).

Bioactive terpenoids from Croton laui.

Two new highly-oxygenated neo-clerodane diterpenoids, 3S-acetoxyl-mollotucin D dilactone ester (1) and 6S-crotoeurin C (2), and a new lupane-type triterpene, 16ß-hydroxyl-3ß-O-trans-coumaroyl-betulin (6), as well as three known analogues (3-5) were obtained from the leaves of Croton laui. The structures of the new compounds were determined by extensive spectroscopic methods, and their absolute configurations were determined by combination of single-crystal X-ray diffraction analysis, electronic circular dichroism (ECD) spectra, and literature data. Compounds 2 and 3 exhibited inhibitory activities of lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW 264.7 macrophages with IC50 values of 1.2 and 1.6 µM, respectively. Additionally, compound 6 exhibited activity against Col205 and HepG2 cell lines with IC50 values of 12.9 and 17.7 µM, respectively.

Triculata A, a novel compound from Tricyrtis maculata (D. Don) J. F. Macbr. with biological properties.

A novel compound, triculata A (1), and seven known compounds were obtained from the Tricyrtis maculata (D. Don) J. F. Macbr.. The structure of the new compound was determined by extensive spectroscopic methods, and its absolute configuration was assigned by single-crystal X-ray diffraction analysis. Compound 1 features a rare naphtho[b,c]pyran carbon skeleton that was found in nature for the first time. Compounds 2-4, 6 and 7 showed potential vasodilatory effects with EC50 values ranging from 7.3 to 111.3 µM. Compounds 1, 3-5 and 7 possessed remarkable antioxidant capacity evaluated by DPPH and ABTS assays.

Pointfilter: Point Cloud Filtering via Encoder-Decoder Modeling.

Point cloud filtering is a fundamental problem in geometry modeling and processing. Despite of significant advancement in recent years, the existing methods still suffer from two issues: 1) they are either designed without preserving sharp features or less robust in feature preservation; and 2) they usually have many parameters and require tedious parameter tuning. In this article, we propose a novel deep learning approach that automatically and robustly filters point clouds by removing noise and preserving their sharp features. Our point-wise learning architecture consists of an encoder and a decoder. The encoder directly takes points (a point and its neighbors) as input, and learns a latent representation vector which goes through the decoder to relate the ground-truth position with a displacement vector. The trained neural network can automatically generate a set of clean points from a noisy input. Extensive experiments show that our approach outperforms the state-of-the-art deep learning techniques in terms of both visual quality and quantitative error metrics. The source code and dataset can be found at https://github.com/dongbo-BUAA-VR/Pointfilter.

Strain gradient induced spatially indirect excitons in single crystalline ZnO nanowires.

Spatially indirect excitons are important not only for the exploration of intriguing many-body effects but also for the development of applications such as solar cells with high efficiency. This type of exciton usually exists in heterostructures. Using the generalized Bloch theorem coupled with the density-functional tight-binding method, we reveal that spatially indirect excitons may emerge in single crystalline ZnO nanowires under bending. The underlying mechanism is attributed to the formation of an effective type-II band alignment due to the strain-gradient of the bent nanowires. Our finding paves a new route to realize spatially indirect excitons by strain engineering.

Licorice-Yuanhua Herbal Pair Induces Ileum Injuries Through Weakening Epithelial and Mucous Barrier Functions: Saponins, Flavonoids, and Di-Terpenes All Involved.

In traditional Chinese Medicine (TCM), the licorice-yuanhua herbal pair is one of the most representative incompatible herbal pairs recorded in the "eighteen incompatible herbal pairs" theory. Previous studies of our research group have demonstrated several gut-related side-effects induced by the licorice-yuanhua herbal pair. In this study, we investigated whether and why this incompatible herbal pair could induce gut tissue damage. After licorice-yuanhua treatment, the duodenum, ileum, and colon and serum biomarkers of mice were examined by pathological staining, Western blot, and ELISA assays. The IEC-6 cells and LS174T cells were treated with licorice saponins, yuanhua flavonoids, and di-terpenes; iTRAQ-labeled proteomic technology was then used to explore their synergistic effects on mucosa cells, followed by verification of ZO-1 and MUC-2 protein expressions. The results showed that the licorice-yuanhua herbal pair induced ileum tissue injuries, including epithelial integrity loss, inflammation, and edema. These injuries were verified to be related to epithelial and mucous barrier weakening, such as downregulated ileum ZO-1 and MUC-2 protein expressions. Proteomic analysis also suggested that glycyrrhizic acid and genkwanin synergistically influence tight junction pathways in LS174T cells. Furthermore, licorice saponins, yuanhua flavonoids, and di-terpenes dose/structure-dependently downregulate ZO-1 and MUC-2 protein expressions in mucosa cells. Our study provides different insights into the incompatibility mechanisms and material basis of the licorice-yuanhua herbal pair, especially that besides toxic di-terpenes, licorice saponins and yuanhua flavonoids, which are commonly known to be non-toxic compounds, can also take part in the gut damage induced by the licorice-yuanhua herbal pair.

Strain induced spin-splitting and half-metallicity in antiferromagnetic bilayer silicene under bending.

Searching for half-metals in low dimensional materials is not only of scientific importance, but also has important implications for the realization of spintronic devices on a small scale. In this work, we show theoretically that simple bending can induce spin-splitting in bilayer silicene. For bilayer silicene with Bernal stacking, the monolayer has a long range ferromagnetic spin order and between the two monolayers, the spin orders are opposite, giving rise to an antiferromagnetic configuration for the ground state of the bilayer silicene. Under bending, the antiferromagnetic spin order is retained but the energetic degeneracy of opposite spin states is lifted. Due to the unusual deformation potentials of the conduction band minimum (CBM) and valence band maximum (VBM) as revealed by density-functional theory calculations and density-functional tight-binding calculations, this spin-splitting is nearly proportional to the degree of bending deformation. Consequently, the spin-splitting can be significant and the desired half-metallic state may emerge when the bending increases, which has been verified by direct simulation of the bent bilayer silicene using the generalized Bloch theorem. Our results hint that bilayer silicene may be an excellent candidate for half-metallicity.

Guchang Zhixie Wan protects mice against dextran sulfate sodium-induced colitis through modulating the gut microbiota in colon.

ETHNOPHARMACOLOGICAL RELEVANCE: Guchang Zhixie Wan (GC) is a traditional Chinese patent medicine used in the treatment of colitis in clinical trials. Though the notable effect of GC on colitis, the concrete mechanism of GC remain elusive. Emerging evidence showed that the imbalances of inflammatory cytokines and gut microbiota were both closely related to the initiation and progression of colitis. AIM OF THE STUDY: To elucidate the relationship between the protective effects of GC on colitis and gut microbiota. MATERIALS AND METHODS: Male Kunming (KM) mice were enrolled in our work to establish colitis model induced by dextran sulfate sodium (DSS). The colitis mice were randomly divided into different groups and treated orally with 125 mg/kg of sulfasalazine (positive control) and 25, 50, 100 mg/kg of GC for 7 days, respectively. Inflammation cytokines of IL-1ß, IL-4, IL-6, IL-8, IL-11, IL-12 and TNF-α were detected by ELISA analysis and the histological changes were detected by H&E staining. Gut microbiota diversity was analyzed by 16S rDNA sequencing. Metagenomes analysis were also conducted to reflect the protective effects of GC on colitis. RESULTS: The results of CAS (Clinical Activity Score) confirmed the protective effects of GC on colitis. After administration of GC, the levels of pro-inflammatory cytokines IL-1ß, IL-6, IL-8, IL-11, IL-12 and TNF-α were all decreased while the anti-inflammatory cytokines IL-4 was slightly increased, indicating that GC could down regulate pro-inflammatory cytokines. H&E staining revealed that GC could improve the histopathological structure of the colon tissue. The results of 16S rDNA sequences analysis showed that GC could decrease the relative abundance of Turicibacter and increase the relative abundance of Ruminococcaceae_UCG-005. CONCLUSION: GC greatly improve the health condition of colitis mice induced by DSS through improving the imbalances of inflammatory cytokines and gut microbiota.

Formation of Bloch Flat Bands in Polar Twisted Bilayers without Magic Angles.

The existence of Bloch flat bands of electrons provides a facile pathway to obtain exotic quantum phases owing to strong correlation. Despite the established magic angle mechanism for twisted bilayer graphene, understanding of the emergence of flat bands in twisted bilayers of two-dimensional polar crystals remains elusive. Here, we show that due to the polarity between constituent elements in the monolayer, the formation of complete flat bands in twisted bilayers is triggered as long as the twist angle is less than a certain critical value. Using the twisted bilayer of hexagonal boron nitride (hBN) as an example, our simulations using the density-functional tight-binding method reveal that the flat band originates from the stacking-induced decoupling of the highest occupied (lowest unoccupied) states, which predominantly reside in the regions of the moiré superlattice where the anion (cation) atoms in both layers are overlaid. Our findings have important implications for the future search for and study of flat bands in polar materials.

Unconventional deformation potential and half-metallicity in zigzag nanoribbons of 2D-Xenes.

Realization of half-metallicity (HM) in low dimensional materials is a fundamental challenge for nano spintronics and a critical component for developing alternative generations of information technology. Using first-principles calculations, we reveal an unconventional deformation potential for zigzag nanoribbons (NRs) of 2D-Xenes. Both the conduction band minimum (CBM) and valence band maximum (VBM) of the edge states have negative deformation potentials. This unique property, combined with the localization and spin-polarization of the edge states, enables us to induce spin-splitting and HM using an inhomogeneous strain pattern, such as simple in-plane bending. Indeed, our calculation using the generalized Bloch theorem reveals the predicted HM in bent zigzag silicene NRs. Furthermore, the magnetic stability of the long range magnetic order for the spin-polarized edge states is maintained well against the bending deformation. These aspects indicate that it is a promising approach to realize HM in low dimensions with the zigzag 2D-Xene NRs.