Network pharmacology, molecular docking and experimental study of CEP in nasopharyngeal carcinoma.

ETHNOPHARMACOLOGICAL RELEVANCE: The Stephania cephalantha Hayata is an important traditional medicinal plant widely used in traditional medicine to treat cancer. Cepharanthine (CEP) was extracted from the roots of Stephania cephalantha Hayata. It has been found to exhibit anticancer activity in different types of cancer cells. Nevertheless, the activity of CEP against nasopharyngeal carcinoma (NPC) and its underlying mechanism warrant further investigation. AIMS OF THE STUDY: NPC is an invasive and highly metastatic malignancy that affects the head and neck region. This research aimed to investigate the pharmacological properties and underlying mechanism of CEP against NPC, aiming to offer novel perspectives on treating NPC using CEP. MATERIALS AND METHODS: In vitro, the pharmacological activity of CEP against NPC was evaluated using the CCK-8 assay. To predict and elucidate the anticancer mechanism of CEP against NPC, we employed network pharmacology, conducted molecular docking analysis, and performed Western blot experiments. In vivo validation was performed through a nude mice xenograft model of human NPC, Western blot and immunohistochemical (IHC) assays to confirm pharmacological activity and the mechanism. RESULTS: In a dose-dependent manner, the proliferation and clonogenic capacity of NPC cells were significantly inhibited by CEP. Additionally, NPC cell migration was suppressed by CEP. The results obtained from network pharmacology experiments revealed that anti-NPC effect of CEP was associated with 8 core targets, including EGFR, AKT1, PIK3CA, and mTOR. By performing molecular docking, the binding capacity of CEP to the candidate core proteins (EGFR, AKT1, PIK3CA, and mTOR) was predicted, resulting in docking energies of -10.0 kcal/mol for EGFR, -12.4 kcal/mol for PIK3CA, -10.8 kcal/mol for AKT1, and -8.6 kcal/mol for mTOR. The Western blot analysis showed that CEP effectively suppressed the expression of EGFR and the phosphorylation levels of downstream signaling proteins, including PI3K, AKT, mTOR, and ERK. After CEP intervention, a noteworthy decrease in tumor size, without inducing any toxicity, was observed in NPC xenograft nude mice undergoing in vivo treatment. Additionally, IHC analysis demonstrated a significant reduction in the expression levels of EGFR and Ki-67 following CEP treatment. CONCLUSION: CEP exhibits significant pharmacological effects on NPC, and its mechanistic action involves restraining the activation of the EGFR/PI3K/AKT pathway. CEP represents a promising pharmaceutical agent for addressing and mitigating NPC.

Copper-Catalyzed Enantioselective Formal [4 + 1] and [3 + 3] Cycloaddition of Ethynylethylene Carbonates.

Herein we employed ethynylethylene carbonates (EECs) to achieve formal [4 + 1] and [3 + 3] cycloaddition with cyclic 1,3-dicarbonyl compounds. On one hand, EECs with styryl substitution could undergo a remotely controlled enantioselective [4 + 1] cycloaddition reaction. This reaction exhibits good chemoselectivity, regioselectivity, and enantioselectivity. In addition, a [3 + 3] cycloaddition reaction of EECs with cyclic 1,3-dicarbonyl compounds was also achieved, leading to a series of 4H-pyrans with impressive chemoselectivity and enantioselectivity.

Synthesis of medium-sized heterocycles from oxetanes based on an allylic amination/ring-opening strategy.

The construction of medium-sized ring compounds has been a prominent research area in synthetic chemistry. In this study, we developed a tandem strategy that combines allylic amination and ring-opening of oxetanes to synthesize medium-sized heterocycles. Specifically, N-aryl oxetan-3-amines undergo allylic amination with zwitterionic π-allylpalladium, followed by intramolecular ring-opening, resulting in the formation of medium-sized heterocycles. Notably, we are able to achieve the synthesis of 7-8 membered heterocycles with moderate to good yields by employing different types of zwitterionic π-allylpalladium species.

A social-semantic working-memory account for two canonical language areas.

Language and social cognition are traditionally studied as separate cognitive domains, yet accumulative studies reveal overlapping neural correlates at the left ventral temporoparietal junction (vTPJ) and the left lateral anterior temporal lobe (lATL), which have been attributed to sentence processing and social concept activation. We propose a common cognitive component underlying both effects: social-semantic working memory. We confirmed two key predictions of our hypothesis using functional MRI. First, the left vTPJ and lATL showed sensitivity to sentences only when the sentences conveyed social meaning; second, these regions showed persistent social-semantic-selective activity after the linguistic stimuli disappeared. We additionally found that both regions were sensitive to the socialness of non-linguistic stimuli and were more tightly connected with the social-semantic-processing areas than with the sentence-processing areas. The converging evidence indicates the social-semantic working-memory function of the left vTPJ and lATL and challenges the general-semantic and/or syntactic accounts for the neural activity of these regions.

Snail-inspired AFG/GelMA hydrogel accelerates diabetic wound healing via inflammatory cytokines suppression and macrophage polarization.

Diabetic foot ulcers (DFUs) are a severe and rapidly growing diabetic complication, but treating DFUs remains a challenge for the existing therapies are expensive and highly non-responsive. Recently, we discovered that a natural adhesive from snail mucus can promote skin wound healing. Herein, inspired by the finding, we developed a double-network hydrogel biomaterial that composed of snail glycosaminoglycan (AFG) and methacrylated gelatin (GelMA), in which AFG is the main bioactive component of snail mucus and GelMA provides a scaffold mimicking the proteins in snail mucus. The biomimetic hydrogel exhibited strong tissue adhesion, potent anti-inflammatory activity, and excellent biocompatibility. The biodegradable AFG/GelMA hydrogel markedly promoted chronic wound healing in both STZ-induced type 1 diabetic rat and db/db mouse models after a single treatment. Further mechanistic research showed that the hydrogel significantly attenuated inflammation by sequestrating pro-inflammatory cytokines, as well as downregulated their expression by inhibiting NF-ĸB signaling pathway, and it can also promote macrophage polarization to M2 phenotype. Taken together, the bioinspired hydrogel can effectively promote the transition of chronic wounds from inflammation to proliferation stage. These data suggest that the AFG/GelMA hydrogel is a promising therapeutic biomaterial for the treatment of chronic diabetic wounds.

SCCNet: Self-correction boundary preservation with a dynamic class prior filter for high-variability ultrasound image segmentation.

The highly ambiguous nature of boundaries and similar objects is difficult to address in some ultrasound image segmentation tasks, such as neck muscle segmentation, leading to unsatisfactory performance. Thus, this paper proposes a two-stage network called SCCNet (self-correction context network) using a self-correction boundary preservation module and class-context filter to alleviate these problems. The proposed self-correction boundary preservation module uses a dynamic key boundary point (KBP) map to increase the capability of iteratively discriminating ambiguous boundary points segments, and the predicted segmentation map from one stage is used to obtain a dynamic class prior filter to improve the segmentation performance at Stage 2. Finally, three datasets, Neck Muscle, CAMUS and Thyroid, are used to demonstrate that our proposed SCCNet outperforms other state-of-the art methods, such as BPBnet, DSNnet, and RAGCnet. Our proposed network shows at least a 1.2-3.7% improvement on the three datasets, Neck Muscle, Thyroid, and CAMUS. The source code is available at https://github.com/lijixing0425/SCCNet.

Le Petit Prince multilingual naturalistic fMRI corpus.

Neuroimaging using more ecologically valid stimuli such as audiobooks has advanced our understanding of natural language comprehension in the brain. However, prior naturalistic stimuli have typically been restricted to a single language, which limited generalizability beyond small typological domains. Here we present the Le Petit Prince fMRI Corpus (LPPC-fMRI), a multilingual resource for research in the cognitive neuroscience of speech and language during naturalistic listening (OpenNeuro: ds003643). 49 English speakers, 35 Chinese speakers and 28 French speakers listened to the same audiobook The Little Prince in their native language while multi-echo functional magnetic resonance imaging was acquired. We also provide time-aligned speech annotation and word-by-word predictors obtained using natural language processing tools. The resulting timeseries data are shown to be of high quality with good temporal signal-to-noise ratio and high inter-subject correlation. Data-driven functional analyses provide further evidence of data quality. This annotated, multilingual fMRI dataset facilitates future re-analysis that addresses cross-linguistic commonalities and differences in the neural substrate of language processing on multiple perceptual and linguistic levels.

Neural correlates of semantic number: A cross-linguistic investigation.

One aspect of natural language comprehension is understanding how many of what or whom a speaker is referring to. While previous work has documented the neural correlates of number comprehension and quantity comparison, this study investigates semantic number from a cross-linguistic perspective with the goal of identifying cortical regions involved in distinguishing plural from singular nouns. Three fMRI datasets are used in which Chinese, French, and English native speakers listen to an audiobook of a children's story in their native language. These languages are selected because they differ in their number semantics. Across these languages, several well-known language regions manifest a contrast between plural and singular, including the pars orbitalis, pars triangularis, posterior temporal lobe, and dorsomedial prefrontal cortex. This is consistent with a common brain network supporting comprehension across languages with overt as well as covert number-marking.

Decoding the silence: Neural bases of zero pronoun resolution in Chinese.

Chinese is one of many languages that can drop subjects. We report an fMRI study of language comprehension processes in these "zero pronoun" cases. The fMRI data come from Chinese speakers who listened to an audiobook. We conducted both univariate GLM and multivariate pattern analysis (MVPA) on these data. We found increased left Temporal Lobe activity for zero pronouns compared to overt subjects, suggesting additional effort searching for an antecedent during zero pronoun resolution. MVPA further revealed that the intended referent of a zero pronoun can be decoded in the Parahippocampal Gyrus and the Precuneus shortly after its presentation. This highlights the role of memory and discourse-level processing in resolving referential expressions, including unspoken ones, in naturalistic language comprehension.

Disentangling Semantic Composition and Semantic Association in the Left Temporal Lobe.

Although composing two words into a complex representation (e.g., "coffee cake") is conceptually different from forming associations between a pair of words (e.g., "coffee, cake"), the brain regions supporting semantic composition have also been implicated for associative encoding. Here, we adopted a two-word magnetoencephalography (MEG) paradigm which varies compositionality ("French/Korean cheese" vs "France/Korea cheese") and strength of association ("France/French cheese" vs "Korea/Korean cheese") between the two words. We collected MEG data while 42 English speakers (24 females) viewed the two words successively in the scanner, and we applied both univariate regression analyses and multivariate pattern classification to the source estimates of the two words. We show that the left anterior temporal lobe (LATL) and left middle temporal lobe (LMTL) are distinctively modulated by semantic composition and semantic association. Specifically, the LATL is mostly sensitive to high-association compositional phrases, while the LMTL responds more to low-association compositional phrases. Pattern-based directed connectivity analyses further revealed a continuous information flow from the anterior to the middle temporal region, suggesting that the integration of adjective and noun properties originated earlier in the LATL is consistently delivered to the LMTL when the complex meaning is newly encountered. Taken together, our findings shed light into a functional dissociation within the left temporal lobe for compositional and distributional semantic processing.SIGNIFICANCE STATEMENT Prior studies on semantic composition and associative encoding have been conducted independently within the subfields of language and memory, and they typically adopt similar two-word experimental paradigms. However, no direct comparison has been made on the neural substrates of the two processes. The current study relates the two streams of literature, and appeals to audiences in both subfields within cognitive neuroscience. Disentangling the neural computations for semantic composition and association also offers insight into modeling compositional and distributional semantics, which has been the subject of much discussion in natural language processing and cognitive science.

Arthriniumsteroids A-D, four new steroids from the soft coral-derived fungus Simplicillium lanosoniveum SCSIO41212.

Four new steroids derivatives, namely arthriniumsteroids A - D (1-4), together with two known compounds, were isolated from the soft coral-derived fungus Simplicillium lanosoniveum SCSIO41212. Their structures were elucidated by spectroscopic analysis and by comparison with those reported in the literature. The absolute configuration of 2 was confirmed by single-crystal X-ray diffraction. In bioassay, all compounds showed weak inhibitory activities against lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW 264.7 cells.

Two new bioactive polyphenols from the soft coral-derived fungus Talaromyces sp. SCSIO 041201.

Two new polyphenols, talaversatilis A (1) and B (2), together with fifteen known compounds (3-17) were isolated from the extract of the culture broth of a soft coral-derived fungus Talaromyces sp. SCSIO 041201. The structures of these compounds were elucidated by the extensive analyses of spectroscopic data and by comparison with the reported literature. Antifouling and antibacterial activities of all purified compounds were tested and evaluated. Compounds 5 and 6 showed antifouling activity towards Bugula neritina larva, with LC50 values of 3.86 µg/mL and 3.05 µg/mL, respectively. Compounds 7, 8, 10 and 13 exhibited significant antibacterial activities against E. coli, MRSA, S. aureus and E. faecalis, with MIC values ranging from 0.45 to 15.6 µg/mL.

Rh(iii)-Catalyzed regioselective mono- and di-iodination of azobenzenes using alkyl iodide.

A new approach for highly regioselective iodination of azobenzenes with alkyl iodide as the iodinating reagent enabled by Rh-catalyzed oxidative C-H activation has been developed. By changing the oxidant, various mono- and di-iodinated azobenzenes were smoothly obtained in moderate to excellent yields, respectively. The preliminary mechanistic study reveals that the reaction process might undergo electrophilic substitution of the directed ortho metalated five-membered rhodacycle compound by an iodine cationic species generated in situ from alkyl iodide and oxidant.

What drives sound symbolism? Different acoustic cues underlie sound-size and sound-shape mappings.

Sound symbolism refers to the non-arbitrary mappings that exist between phonetic properties of speech sounds and their meaning. Despite there being an extensive literature on the topic, the acoustic features and psychological mechanisms that give rise to sound symbolism are not, as yet, altogether clear. The present study was designed to investigate whether different sets of acoustic cues predict size and shape symbolism, respectively. In two experiments, participants judged whether a given consonant-vowel speech sound was large or small, round or angular, using a size or shape scale. Visual size judgments were predicted by vowel formant F1 in combination with F2, and by vowel duration. Visual shape judgments were, however, predicted by formants F2 and F3. Size and shape symbolism were thus not induced by a common mechanism, but rather were distinctly affected by acoustic properties of speech sounds. These findings portray sound symbolism as a process that is not based merely on broad categorical contrasts, such as round/unround and front/back vowels. Rather, individuals seem to base their sound-symbolic judgments on specific sets of acoustic cues, extracted from speech sounds, which vary across judgment dimensions.

Assembly of Diversely Substituted Quinolines via Aerobic Oxidative Aromatization from Simple Alcohols and Anilines.

An aerobic oxidative aromatization of simple aliphatic alcohols and anilines under the Pd(OAc)2/2,4,6-Collidine/Brønsted acid catalytic system has been established, providing a direct approach for the preparation of diverse substituted quinoline derivatives in high yields with wide functional group tolerance. Practically, the protocol can be easily scaled up to gram-scale and was utilized in the concise formal synthesis of a promising herbicide candidate.

A Green Aerobic Oxidative Synthesis of Pyrrolo[1,2-a]quinoxalines from Simple Alcohols without Metals and Additives.

A practical and concise protocol for the efficient preparation of pyrrolo[1,2-a]quinoxalines through a cascade of alcohol oxidation/imine formation/intramolecular cyclization/oxidative dehydrogenation has been established. A series of substituted pyrrolo[1,2-a]quinoxaline derivatives were constructed readily in yields of 53-93% from the cheap primary alcohols by using dioxygen as the terminal oxidant. Remarkably, the fact that no extra metals and additives were necessary makes this unprecedented aerobic oxidation process highly step- and atom-economical. The usefulness of this transformation was further demonstrated with the gram-scale synthesis of compound 3aa under standard conditions.

AgNO3 as nitrogen source for rhodium(iii)-catalyzed synthesis of 2-aryl-2H-benzotriazoles from azobenzenes.

A new approach has been established for Rh(iii)-catalyzed direct aza oxidative cyclization of non-prefunctionalized azobenzenes to provide 2-aryl-2H-benzotriazoles in good yields, in which AgNO3 instead of conventional azide reagents for the first time functions as the nitrogen source for the nitrogenation reaction. Preliminary mechanistic studies suggest that the Rh(iii)-catalyst could account for the nitration reaction, and subsequently cationic silver species might both play a vital role in the fission of the nitrogen-oxygen bonds in nitro groups and promote aza oxidative cyclization.

Triarylphosphines as Aryl Donors for Pd(II)-Catalyzed Aromatic Coupling of Oxabenzonorbornadienes.

A new approach was developed for Pd(II)-catalyzed aromatic coupling of oxabenzonorbornadienes with triarylphosphines as both ligands and aryl donors. Diverse functional groups including halo- (F-, Cl-, and Br-), CF3(-), and furyl groups are well tolerated. For unsymmetrical triarylphosphines, the migration ability of aryls is consistent with the electronic property of substituents and maintains the order EDG-Ar > H-Ar > EWD-Ar (EDG means electron-donating group, EWG means electron-withdrawing group). A preliminary mechanistic study was also disclosed.