NFKB2 mediates colorectal cancer cell immune escape and metastasis in a STAT2/PD­L1­dependent manner.

This study systematically analyzed the molecular mechanism and function of nuclear factor kappa B subunit 2 (NFKB2) in colorectal cancer (CRC) to investigate the potential of NFKB2 as a therapeutic target for CRC. Various experimental techniques, including RNA sequencing, proteome chip assays, and small molecule analysis, were used to obtain a deeper understanding of the regulation of NFKB2 in CRC. The results revealed that NFKB2 was upregulated in a significant proportion of patients with advanced hepatic metastasis of CRC. NFKB2 played an important role in promoting tumor growth through CD8+ T-cell exhaustion. Moreover, NFKB2 directly interacted with signal transducer and activator of transcription 2 (STAT2), leading to increased phosphorylation of STAT2 and the upregulation of programmed death ligand 1 (PD-L1). Applying a small molecule inhibitor of NFKB2 (Rg5) led to a reduction in PD-L1 expression and improved response to programmed death-1 blockade-based immunotherapy. In conclusion, the facilitated NFKB2-STAT2/PD-L1 axis may suppress immune surveillance in CRC and targeting NFKB2 may enhance the efficacy of immunotherapeutic strategies. Our results provide novel insights into the molecular mechanisms underlying the contribution of NFKB2 in CRC immune escape.

Development of Potent MALT1 Inhibitors Featuring a Novel "2-Thioxo-2,3-dihydrothiazolo[4,5-d]pyrimidin-7(6H)-one" Scaffold for the Treatment of B Cell Lymphoma.

Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) has emerged as a novel and promising therapeutic target for the treatment of lymphomas and autoimmune diseases. Herein, we reported a new class of MALT1 inhibitors featuring a novel "2-thioxo-2,3-dihydrothiazolo[4,5-d]pyrimidin-7(6H)-one" scaffold developed by structure-based drug design. Structure-activity relationship studies finally led to the discovery of MALT1 inhibitor 10m, which covalently and potently inhibited MALT1 protease with the IC50 value of 1.7 µM. 10m demonstrated potent and selective antiproliferative activity against ABC-DLBCL and powerful ability to induce HBL1 apoptosis. 10m also effectively downregulated the activities of MALT1 and its downstream signal pathways. Furthermore, 10m induced upregulation of mTOR and PI3K-Akt signals and exhibited a synergistic antitumor effect with Rapamycin in HBL1 cells. More importantly, 10m remarkably suppressed the tumor growth both in the implanted HBL1 and TMD8 xenograft models. Collectively, this work provides valuable MALT1 inhibitors with a distinct core structure.

Pathogenicity and landscape of differential gene expression in mice orally infected with clinical coxsackievirus A6 (CA6).

Hand, foot, and mouth disease (HFMD) is caused by more than 20 pathogenic enteroviruses belonging to the Picornaviridae family and Enterovirus genus. Since the introduction of the enterovirus-71 (EV71) vaccine in 2016, the number of HFMD cases caused by EV71 has decreased. However, cases of infections caused by other enteroviruses, such as coxsackievirus A6 (CA6) and coxsackievirus A10, have been increasing accordingly. In this study, we used a clinical isolate of CA6 to establish an intragastric infection mouse model using 7-day-old mice to mimic the natural transmission route, by which we investigated the differential gene expression profiles associated with virus infection and pathogenicity. After intragastric infection, mice exhibited hind limb paralysis symptoms and weight loss, similar to those reported for EV71 infection in mice. The skeletal muscle was identified as the main site of virus replication, with a peak viral load reaching 2.31 × 107 copies/mg at 5 dpi and increased infiltration of inflammatory cells. RNA sequencing analysis identified differentially expressed genes (DEGs) after CA6 infection. DEGs in the blood, muscle, brain, spleen, and thymus were predominantly enriched in immune system responses, including pathways such as Toll-like receptor signaling and PI3K-Akt signaling. Our study has unveiled the genes involved in the host immune response during CA6 infection, thereby enhancing our comprehension of the pathological mechanism of HFMD.IMPORTANCEThis study holds great significance for the field of hand, foot, and mouth disease (HFMD). It not only delves into the disease's etiology, transmission pathways, and severe complications but also establishes a novel mouse model that mimics the natural coxsackievirus A6 infection process, providing a pivotal platform to delve deeper into virus replication and pathogenic mechanisms. Additionally, utilizing RNA-seq technology, it unveils the dynamic gene expression changes during infection, offering valuable leads for identifying novel therapeutic drug targets. This research has the potential to enhance our understanding of HFMD, offering fresh perspectives for disease prevention and treatment and positively impacting children's health worldwide.

The Role of Neutrophil in COVID-19: Positive or Negative.

BACKGROUND: Neutrophils are the first line of defense against pathogens. They are divided into multiple subpopulations during development and kill pathogens through various mechanisms. Neutrophils are considered one of the markers of severe COVID-19. SUMMARY: In-depth research has revealed that neutrophil subpopulations have multiple complex functions. Different subsets of neutrophils play an important role in the progression of COVID-19. KEY MESSAGES: In this review, we provide a detailed overview of the developmental processes of neutrophils at different stages and their recruitment and activation after SARS-CoV-2 infection, aiming to elucidate the changes in neutrophil subpopulations, characteristics, and functions after infection and provide a reference for mechanistic research on neutrophil subpopulations in the context of SARS-CoV-2 infection. In addition, we have also summarized research progress on potential targeted drugs for neutrophil immunotherapy, hoping to provide information that aids the development of therapeutic drugs for the clinical treatment of critically ill COVID-19 patients.

Predicting the global potential distribution of two major vectors of Rocky Mountain Spotted Fever under conditions of global climate change.

Rocky Mountain spotted fever is a tick-borne disease that is highly dangerous but often overlooked by the public. To prevent the spread of the disease, it is important to understand the distribution patterns of its vectors' suitable areas. This study aims to explore the potential global suitability of areas for the vectors of Rocky Mountain spotted fever, including Dermacentor variabilis and Amblyomma cajennense under both historical and future climate scenarios. The study also seeks to investigate the impact of climatic factors on the distribution patterns of these vectors. Data on species distribution were downloaded from the Global Biodiversity Information Facility, Web of Science and PubMed database. The climatic variables were downloaded from WorldClim Global Climate Database. The Maximum Entropy Model was used to evaluate the contribution of monthly precipitation, monthly maximum temperature, monthly minimum temperature, elevation, and nineteen other climatic variables to vector survival, as well as to predict the suitable area for the vectors. We found that D. variabilis is distributed in North America, while A. cajennense is mainly distributed in South America, but all other continents except Antarctica have a suitable distribution. D. variabilis is more likely to survive in temperate regions, and A. cajennense is more likely to survive in tropical zones. D. variabilis is more sensitive to temperature, whereas A. cajennense is sensitive to both temperature and precipitation, and A. cajennense prefers tropical regions with hot and humid characteristics. The high suitable areas of both vectors were almost expanded in the ssp5-8.5 scenario, but not so much in the ssp1-2.6 scenario. Highly suitable areas with vectors survival should be strengthened with additional testing to prevent related diseases from occurring, and other highly suitable areas should be alert for entry and exit monitoring to prevent invasion and colonization of vectors.

Industrializable and pH-tolerant electropositive imidazolium chloride polymer for high-efficiency removal of perfluoroalkyl carboxylic acids from aqueous solution.

In recent years, various materials have been used to adsorb and remove perfluoroalkyl compounds from water. However, most of these materials have limited applications due to their high cost, complex synthesis, inadequate selectivity and sensitivity, and, even worse, the possibility of introducing secondary pollution. Here, under mild conditions, we prepared an inexpensive imidazolium chloride and nitrogen-rich polymer (TAGX-Cl) with a high cationic loading rate and a high yield (>82%). The adsorbent exhibits excellent pH tolerance (pH=1-9) and achieves nearly 99.9% removal of nine perfluoroalkyl carboxylic acids (PFCAs) within 120 min. Experimental data and theoretical simulations confirmed that synergistic electrostatic interactions, hydrogen bonds, and P-π interactions control the adsorptive ability of TAGX-Cl. This work provides a practical strategy for PFCAs removal.

Click-Pixel Cognition Fusion Network With Balanced Cut for Interactive Image Segmentation.

Interactive image segmentation (IIS) has been widely used in various fields, such as medicine, industry, etc. However, some core issues, such as pixel imbalance, remain unresolved so far. Different from existing methods based on pre-processing or post-processing, we analyze the cause of pixel imbalance in depth from the two perspectives of pixel number and pixel difficulty. Based on this, a novel and unified Click-pixel Cognition Fusion network with Balanced Cut (CCF-BC) is proposed in this paper. On the one hand, the Click-pixel Cognition Fusion (CCF) module, inspired by the human cognition mechanism, is designed to increase the number of click-related pixels (namely, positive pixels) being correctly segmented, where the click and visual information are fully fused by using a progressive three-tier interaction strategy. On the other hand, a general loss, Balanced Normalized Focal Loss (BNFL), is proposed. Its core is to use a group of control coefficients related to sample gradients and forces the network to pay more attention to positive and hard-to-segment pixels during training. As a result, BNFL always tends to obtain a balanced cut of positive and negative samples in the decision space. Theoretical analysis shows that the commonly used Focal and BCE losses can be regarded as special cases of BNFL. Experiment results of five well-recognized datasets have shown the superiority of the proposed CCF-BC method compared to other state-of-the-art methods. The source code is publicly available at https://github.com/lab206/CCF-BC.

SOSNet: Real-Time Small Object Segmentation via Hierarchical Decoding and Example Mining.

Real-time semantic segmentation plays an important role in auto vehicles. However, most real-time small object segmentation methods fail to obtain satisfactory performance on small objects, such as cars and sign symbols, since the large objects usually tend to devote more to the segmentation result. To solve this issue, we propose an efficient and effective architecture, termed small objects segmentation network (SOSNet), to improve the segmentation performance of small objects. The SOSNet works from two perspectives: methodology and data. Specifically, with the former, we propose a dual-branch hierarchical decoder (DBHD) which is viewed as a small-object sensitive segmentation head. The DBHD consists of a top segmentation head that predicts whether the pixels belong to a small object class and a bottom one that estimates the pixel class. In this situation, the latent correlation among small objects can be fully explored. With the latter, we propose a small object example mining (SOEM) algorithm for balancing examples between small objects and large objects automatically. The core idea of the proposed SOEM is that most of the hard examples on small-object classes are reserved for training while most of the easy examples on large-object classes are banned. Experiments on three commonly used datasets show that the proposed SOSNet architecture greatly improves the accuracy compared to the existing real-time semantic segmentation methods while keeping efficiency. The code will be available at https://github.com/StuLiu/SOSNet.

Abietane diterpenoids and iridoids from Caryopteris mongolica.

Six new abietane diterpenoids (1-6) and five undescribed iridoids (7-11) have been isolated from the aerial parts of Caryopteris mongolica. The intricate structural characterization of these compounds was meticulously undertaken using an array of advanced spectroscopic techniques. This process was further enhanced by the application of DP4+ probability analyses and electronic circular dichroism (ECD) calculations. Following isolation and structural elucidation, the cytotoxicity of these compounds was evaluated. Among them, compound 3 stood out, displaying significant cytotoxic activity against HeLa cells with an IC50 value of 7.83 ± 1.28 µmol·L-1. Additionally, compounds 1, 2, 4, 9, and 10 manifested moderate cytotoxic effects on specific cell lines, with IC50 values ranging from 11.7 to 20.9 µmol·L-1.

Disparities of Heatwave-Related Preterm Birth in Climate Types - China, 2012-2019.

What is already known about this topic?: An association between prenatal heatwave exposure and the risk of preterm birth was found. However, the disparities in heatwave-related preterm birth across different climate types have not been examined. What is added by this report?: This nationwide case-crossover study investigated the association between heatwave exposure and preterm birth across different Köppen-Geiger climate types. Among pregnant women residing in the arid-desert-cold climate type, exposure to compound heatwaves was found to be associated with a significantly higher risk of preterm birth {adjusted odds ratios (AORs) ranged from 1.55 [95% confidence interval ( CI): 1.21-1.97] to 2.11 (95% CI: 1.35-3.31)}. In contrast, among pregnant women residing in the tropical monsoonal climate type, exposure to daytime-only heatwaves was associated with an increased risk of preterm birth [AORs ranged from 1.25 (95% CI: 1.03-1.51) to 1.37 (95% CI: 1.05-1.77)]. What are the implications for public health practice?: Specific interventions should be implemented in China to mitigate the risk of preterm birth related to heatwaves, particularly for pregnant women residing in arid-desert-cold and tropical monsoonal climates.

Single-Cell Diagnosis of Cancer Drug Resistance through the Differential Endocytosis of Nanoparticles between Drug-Resistant and Drug-Sensitive Cancer Cells.

Single-cell diagnosis of cancer drug resistance is highly relevant for cancer treatment, as it can be used to identify the subpopulations of drug-resistant cancer cells, reveal the sensitivity of cancer cells to treatment, and monitor the progress of cancer drug resistance. However, simple and effective methods for cancer drug resistance detection at the single-cell level are still lacking in laboratory and clinical studies. Inspired by the fact that nanoparticles with diverse physicochemical properties would generate distinct and specific interactions with drug-resistant and drug-sensitive cancer cells, which have distinctive molecular signatures, here, we have synthesized a library of fluorescent nanoparticles with various sizes, surface charges, and compositions (SiO2 nanoparticles (SNPs), organic PS-co-PAA nanoparticles (ONPs), and ZIF-8 nanoparticles (ZNPs)), thus demonstrating that the composition has a critical influence on the interaction of nanoparticles with drug-resistant cancer cells. Furthermore, the clathrin/caveolae-independent endocytosis of ZNPs together with the P-glycoprotein-related decreased cell membrane fluidity resulted in a lower cellular accumulation of ZNPs in drug-resistant cancer cells, consequently causing the distinct cellular accumulation of ZNPs between the drug-resistant and drug-sensitive cancer cells. This difference was further quantified by detecting the fluorescence signals generated by the accumulation of nanoparticles at the single-cell level via flow cytometry. Our findings provide another insight into the nanoparticle-cell interactions and offer a promising platform for the diagnosis of cancer drug resistance of various cancer cells and clinical cancer samples at the single-cell level.

Trends and future projections of liver cancer incidence in Hong Kong: a population-based study.

BACKGROUND: Liver cancer remains a significant burden in Hong Kong. We sought to examine trends in liver cancer incidence using 30 years of cancer registry data in Hong Kong. Additionally, we aimed to assess the impact of age, period and birth cohort on liver cancer incidence, provided projections for liver cancer incidence until 2030, and examined the drivers of liver cancer incidence. METHODS: Data on liver cancer incidence were collected from the Hong Kong Cancer Registry (HKCaR). We assessed age, period, and birth cohort effects using age-period-cohort (APC) models. We employed Bayesian APC analysis with integrated nested Laplace approximations to project the future burden of liver cancer in Hong Kong. Furthermore, we attributed the changes in new liver cancer cases to population growth, population ageing, and epidemiological changes. RESULTS: The study included a total of 51,333 individuals, of whom 39,287 (76.53%) were male. From 1991 to 2020, the age-standardized liver cancer incidence rate in Hong Kong continued declining, while the number of new cases increased significantly, especially among males. The net drift, representing the overall annual percentage change of the age-adjusted rate, was - 3.06% (95% confidence interval [CI]: -3.31% to -2.80%) for males and - 3.85% (95% CI: -4.61% to -3.09%) for females. Local drift, which estimates the annual percentage change over time specific to age group, decreased in all age groups for both sexes, with a more pronounced decrease in younger age groups. The period and cohort risk of developing liver cancer also showed decreasing trends for both sexes. The study projected a decline in liver cancer cases for males but an increase for females in Hong Kong, with an estimated 1,083 cases in males and 710 cases in females by 2030. Demographic decomposition analysis revealed that while population growth and ageing were the main drivers of increased liver cancer cases, epidemiologic shifts mostly offset these factors. CONCLUSION: The period and cohort risk of developing liver cancer in Hong Kong declined due to epidemiological changes. Although the age-standardized incidence rates of liver cancer have also declined, demographic and epidemiological factors have led to lower case expectations in males but a likely increase in females. Further research and epidemiological assessment of the disease are needed.

Pixel-Centric Context Perception Network for Camouflaged Object Detection.

Camouflaged object detection (COD) aims to identify object pixels visually embedded in the background environment. Existing deep learning methods fail to utilize the context information around different pixels adequately and efficiently. In order to solve this problem, a novel pixel-centric context perception network (PCPNet) is proposed, the core of which is to customize the personalized context of each pixel based on the automatic estimation of its surroundings. Specifically, PCPNet first employs an elegant encoder equipped with the designed vital component generation (VCG) module to obtain a set of compact features rich in low-level spatial and high-level semantic information across multiple subspaces. Then, we present a parameter-free pixel importance estimation (PIE) function based on multiwindow information fusion. Object pixels with complex backgrounds will be assigned with higher PIE values. Subsequently, PIE is utilized to regularize the optimization loss. In this way, the network can pay more attention to those pixels with higher PIE values in the decoding stage. Finally, a local continuity refinement module (LCRM) is used to refine the detection results. Extensive experiments on four COD benchmarks, five salient object detection (SOD) benchmarks, and five polyp segmentation benchmarks demonstrate the superiority of PCPNet with respect to other state-of-the-art methods.

A Lightweight Pixel-Level Unified Image Fusion Network.

In recent years, deep-learning-based pixel-level unified image fusion methods have received more and more attention due to their practicality and robustness. However, they usually require a complex network to achieve more effective fusion, leading to high computational cost. To achieve more efficient and accurate image fusion, a lightweight pixel-level unified image fusion (L-PUIF) network is proposed. Specifically, the information refinement and measurement process are used to extract the gradient and intensity information and enhance the feature extraction capability of the network. In addition, these information are converted into weights to guide the loss function adaptively. Thus, more effective image fusion can be achieved while ensuring the lightweight of the network. Extensive experiments have been conducted on four public image fusion datasets across multimodal fusion, multifocus fusion, and multiexposure fusion. Experimental results show that L-PUIF can achieve better fusion efficiency and has a greater visual effect compared with state-of-the-art methods. In addition, the practicability of L-PUIF in high-level computer vision tasks, i.e., object detection and image segmentation, has been verified.

Fabrication of pH-dependent solid dispersion for oral colon-targeted delivery of notoginsenoside R1 and its protective effects on ulcerative colitis mice.

Notoginsenoside R1 (R1), which originated from the rhizomes and roots of Panax notoginseng, is classified as a Biopharmaceutical Classification System class III drug with good solubility but poor oral absorption. Although R1 can alleviate the inflammation of dextran sulfate sodium (DSS)-induced colitis in mice, the problem of acid degradation and low bioavailability limit its application. The purpose of this study was aimed to design one kind of pH-dependent solid dispersion for oral colon-targeted delivery of R1. Using Eudragit S100 (ES 100) and PEG 4000 as the pH-dependent carriers, R1 solid dispersion (R1-SD) was fabricated by solvent evaporation method. Scanning electron microscopy, differential scanning calorimetry, and powder X-ray diffraction analysis indicated that R1-SD was completely formed, the surface was smooth surface and the strip crystal structure of R1 disappeared. The in vitro release profile of R1-SD (R1-ES 100-PEG 4000, 1:7:1, weight ratio) exhibited that R1-SD was not released in media simulating the gastric condition (pH 1.2), but better release characteristics of the drug could be obtained in media simulating the intestinal condition (less than 30% in pH 6.8 phosphate-buffered saline and more than 90% in pH 7.6 condition). The in vitro colon absorption test showed that the absorption rate and cumulative release of R1-SD were higher than those of R1. R1-SD and R1 had apparent protective effect on colon shortening, inflammatory infiltrating tissue injury, weight loss, diarrhea, blood stool in mice with ulcerative colitis induced by DSS, and the protective effect of R1-SD was better than that of R1, which indicated R1-SD has good practical application prospects.

Sulfonic acid functionalized monolithic column for high selectivity capillary electrochromatography separation.

A new nano-scale spherical vinyl-functionalized covalent organic polymer (TAPT-DVA-COP) with uniform sizes around 300 nm was initially constructed using 2,5-divinyl-1,4-benzaldehyde (DVA) and 2,4,6-tris(4-aminophenyl)-1,3,5-triazine (TAPT) as monomers. Then, a sulfonic acid (-SO3H) modified COP termed COP-SO3H was developed based on post-sythesis method employing TAPT-DVA-COP as precursor. Capillary electrochromatography (CEC) monolithic columns were fabricated using the physical doping technique to exhibit the application potential of TAPT-DVA-COP and COP-SO3H. Compared to the TAPT-DVA-COP monolithic column, the COP-SO3H monolithic column achieved a highly selective separation between analytes with different properties, including monosubstituted benzenes, alkylbenzenes, hydroxybenzoates, nucleoside bases, and biogenic amines. Non-covalent interaction (NCI) analysis and experimental data show that the synergism of the sulfonic acid group and aromatic moieties on COP-SO3H endows the new stationary phase with diverse interactions, including ion exchange, hydrophobic, π-π and hydrogen bonding. In addition, the COP-SO3H monolithic column exhibited good reproducibility and excellent potential for the determination of hydroxybenzoates in compact powders and alkylbenzenes in effluent samples.

Small-Angle X-ray Scattering for PEGylated Liposomal Doxorubicin Drugs: An Analytical Model Comparison Study.

Liposomal delivery systems are recognized as efficient and safe platforms for chemotherapeutic agents, with doxorubicin-loaded liposomes being the most representative nanopharmaceuticals. Characterizing the structure of liposomal nanomedicines in high spatial and temporal resolution is critical to analyze and evaluate their stability and efficacy. Small-angle X-ray scattering (SAXS) is a powerful tool increasingly used to investigate liposomal delivery systems. In this study, we chose a Doxil-like PEGylated liposomal doxorubicin (PLD) as an example and characterized the liposomal drug structure using synchrotron SAXS. Classical analytical models, including the spherical-shell or flat-slab geometries with Gaussian or uniform electron density profiles, were used to model the internal structure of the liposomal membrane. A cylinder model was applied to fit the scattering from the drug crystal loaded in the liposomes. The high-resolution structures of the original drug, Caelyx, and a similar research drug prepared in our laboratory were characterized using these analytical models. The structural parameters of PLDs, including the thickness of the liposomal membrane and morphology of the drug crystal, were further compared. The results demonstrated that both spherical-shell and flat-slab geometries with Gaussian electron density distribution were suitable to elucidate the structural features of the liposomal membrane under a certain range of scattering vectors, while models with uniform electron density distribution exhibited poor fitting performance. This study highlights the technical features of SAXS, which provides structural information at the nanoscale for liposomal drugs. The demonstrated methods are reliable and easy-to-use for the structural analysis of liposomal drugs, which are helpful for a broader application of SAXS in the production and regulation of nanopharmaceuticals.

Interrelation between the lipid accumulation product index and diabetic kidney disease in patients with type 2 diabetes mellitus.

Objective: The purpose of this study was to determine the relation between the lipid accumulation product index (LAPI) and diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus (T2DM). Methods: Herein, 931 patients were enrolled and their data were collected. Then the interrelation between LAPI and DKD was assessed using multivariate logistic regression analyses (LRAs) and by a restricted cubic spline (RCS). Results: In total, 931 participants (352 females and 579 males) aged 55 years on average were included in the study. After adjusting for several confounders, the odds ratio for DKD was increased evidently in the third LAPI tertile compared with that in the first LAPI tertile. In addition, the RCS revealed a positive interrelation between LAPI and DKD. In the subgroup analyses, age, sex, hyperlipidemia, hypertension, and HbA1c did not significantly interact with LAPI. Conclusions: LAPI was higher in the DKD group than in the no-DKD group, and LAPI is positively linked with DKD, which may have potential value to diagnose DKD in clinical practice.

C21 steroids from the roots of Marsdenia tenacissima.

A phytochemical investigation of the dichloromethane soluble fraction of the ethanolic extract obtained from the roots of Marsdenia tenacissima led to the discovery of the sixteen undescribed pregnane C21 steroids (1-16) and isolation of eleven known C21 steroidal analogues (17-27). Their chemical structures were elucidated by one- and two-dimensional nuclear magnetic resonance spectroscopy and, high resolution-electrospray ionization mass spectrometry and their absolute configurations were determined using electronic circular dichroism or single-crystal X-ray diffraction. The in vitro anti-proliferative effects of 1-16 were evaluated against HepG2 (human hepatocellular cancer), A549 (lung cancer), and MCF-7 (human breast cancer) cell lines. Even though some of them showed moderate cytotoxic activities, marsectohexol derivative 12 exhibited significant cytotoxicity against A549 cells with an IC50 value of 5.2 µM.

Isolation and identification of 3,4-seco-labdane diterpenoids from Callicarpa nudiflora and investigation of their cytotoxicity against HepG2 cells.

Twenty-one previously undescribed compounds, including nineteen 3,4-seco-labdanes (nudiflopenes P-W, Y, AI-JI), one 3,4-seco-pimarane (nudiflopene X), and one labdane (nudiflopene Z), along with nine known compounds (one 3,4-seco-pimarane and eight 3,4-seco-labdanes) were isolated from the leaves of Callicarpa nudiflora Hook. Et Arn. The structures of these compounds were elucidated by high-resolution electrospray ionization mass spectrometry and one- and two-dimensional nuclear magnetic resonance spectroscopy. In addition, configurations of the isolated compounds were determined by electronic circular dichroism, DP4+ probability analysis, and single-crystal X-ray diffraction experiments. All undescribed compounds were evaluated for their cytotoxicity against HepG2 cells in vitro, among which compound 12 exhibited a moderate activity with an IC50 value of 27.8 µM.