Advanced drive laser system for a high-brightness continuous-wave photocathode electron gun.

In order to enhance the performance of a continuous-wave photocathode electron gun at Peking University, and to achieve electron beams with higher current and brightness, a multifunctional drive laser system named PULSE (Peking University drive Laser System for high-brightness Electron source) has been developed. This innovative system is capable of delivering an average output power of 120 W infrared laser pulse at 81.25 MHz, as well as approximately 13.8 W of green power with reliable stability. The utilization of two stages of photonic crystal fibers plays a crucial role in achieving this output. Additionally, the incorporation of two acousto-optic modulators enables the selection of macro-pulses with varying repetition frequencies and duty cycles, which is essential for effective electron beam diagnosis. Furthermore, the system employs a series of birefringent crystals for temporal pulse shaping, allowing for stacking Gaussian pulses into multiple types of distribution. Overall, the optical schematic and operating performance of PULSE are detailed in this paper.

Utilizing GO/PEDOT:PSS/PtNPs-enhanced high-stability microelectrode arrays for investigating epilepsy-induced striatal electrophysiology alterations.

The striatum plays a crucial role in studying epilepsy, as it is involved in seizure generation and modulation of brain activity. To explore the complex interplay between the striatum and epilepsy, we engineered advanced microelectrode arrays (MEAs) specifically designed for precise monitoring of striatal electrophysiological activities in rats. These observations were made during and following seizure induction, particularly three and 7 days post-initial modeling. The modification of graphene oxide (GO)/poly (3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS)/platinu-m nanoparticles (PtNPs) demonstrated a marked reduction in impedance (10.5 ± 1.1 kΩ), and maintained exceptional stability, with impedance levels remaining consistently low (23 kΩ) even 14 days post-implantation. As seizure intensity escalated, we observed a corresponding increase in neuronal firing rates and local field potential power, with a notable shift towards higher frequency peaks and augmented inter-channel correlation. Significantly, during the grand mal seizures, theta and alpha bands became the dominant frequencies in the local field potential. Compared to the normal group, the spike firing rates on day 3 and 7 post-modeling were significantly higher, accompanied by a decreased firing interval. Power in both delta and theta bands exhibited an increasing trend, correlating with the duration of epilepsy. These findings offer valuable insights into the dynamic processes of striatal neural activity during the initial and latent phases of temporal lobe epilepsy and contribute to our understanding of the neural mechanisms underpinning epilepsy.

Effect of nitrogen, phosphorus and potassium fertilization management on soil properties and leaf traits and yield of Sapindus mukorossi.

Rational fertilization is the main measure to improve crop yield, but there are differences in the optimal effects of nitrogen (N), phosphorus (P) and potassium (K) rationing exhibited by the same crop species in different regions and soil conditions. In order to determine the optimum fertilization ratio for high yield of Sapindus mukorossi in western Fujian to provide scientific basis. We carried out the experimental design with different ratios of N, P and K to investigate the effects of fertilization on the yield. and leaf physiology of Sapindus mukorossiand soil properties. Results showed that the yield of Sapindus mukorossi reached the highest value (1464.58 kg ha-1) at N2P2K2 treatment, which increased to 1056.25 kg ha-1 compared with the control. There were significant differences in the responses of soil properties and leaf physiological factors to fertilization treatments. Factor analysis showed that the integrated scores of soil factors and leaf physiological characteristic factors of Sapindus mukorossi under N2P2K2 fertilization treatment were the highest, which effectively improved the soil fertility and leaf physiological traits. The yield of Sapindus mukorossi showed a highly significant linear positive correlation with the integrated scores (r=0.70, p<0.01). Passage analysis showed that soil available nitrogen content, organic carbon content, and leaf area index were the key main factors to affect the yield. RDA showed that soil organic carbon and available phosphorus were the most important factors to affect leaf physiological traits. We recommend that the optimum fertilization ratio of Sapindus mukorossi was 0.96Kg N, 0.80Kg P and 0.64Kg K per plant. Reasonable fertilization can improve soil fertility and leaf physiological traits, while excessive fertilization has negative effects on soil fertility, leaf physiology and yield. This study provides theoretical support for scientific cultivation of woody oil seed species.

ADNP modulates SINE B2-derived CTCF-binding sites during blastocyst formation in mice.

CTCF is crucial for chromatin structure and transcription regulation in early embryonic development. However, the kinetics of CTCF chromatin occupation in preimplantation embryos have remained unclear. In this study, we used CUT&RUN technology to investigate CTCF occupancy in mouse preimplantation development. Our findings revealed that CTCF begins binding to the genome prior to zygotic genome activation (ZGA), with a preference for CTCF-anchored chromatin loops. Although the majority of CTCF occupancy is consistently maintained, we identified a specific set of binding sites enriched in the mouse-specific short interspersed element (SINE) family B2 that are restricted to the cleavage stages. Notably, we discovered that the neuroprotective protein ADNP counteracts the stable association of CTCF at SINE B2-derived CTCF-binding sites. Knockout of Adnp in the zygote led to impaired CTCF binding signal recovery, failed deposition of H3K9me3, and transcriptional derepression of SINE B2 during the morula-to-blastocyst transition, which further led to unfaithful cell differentiation in embryos around implantation. Our analysis highlights an ADNP-dependent restriction of CTCF binding during cell differentiation in preimplantation embryos. Furthermore, our findings shed light on the functional importance of transposable elements (TEs) in promoting genetic innovation and actively shaping the early embryo developmental process specific to mammals.

17ß-estradiol biosensors based on different bioreceptors and their applications.

17ß-Estradiol (E2) is a critical sex steroid hormone, which has significant effects on the endocrine systems of both humans and animals. E2 is also believed to play neurotrophic and neuroprotective roles in the brain. Biosensors present a powerful tool to detect E2 because of their small, efficient, and flexible design. Furthermore, Biosensors can quickly and accurately obtain detection results with only a small sampling amount, which greatly meets the detection of the environment, food safety, medicine safety, and human body. This review focuses on previous studies of biosensors for detecting E2 and divides them into non-biometric sensors, enzyme biosensors, antibody biosensors, and aptamer biosensors according to different bioreceptors. The advantages, disadvantages, and design points of various bioreceptors for E2 detection are analyzed and summarized. Additionally, applications of different bioreceptors of E2 detection are presented and highlight the field of environmental monitoring, food and medicine safety, and disease detection in recent years. Finally, the development of E2 detection by biosensor is prospected.

Protective effect of tretinoin on cervical cancer growth and proliferation through downregulation of pFAK2 expression.

BACKGROUND: Cervical cancer, a life-threatening disease, is the seventh most commonly detected cancer among women throughout the world. The present study investigated the effect of tretinoin on cervical cancer growth and metastasis in vitro and in vivo in the mice model. MATERIALS AND METHODS: Cell Counting Kit-8, clonogenic survival, and transwell chamber assays were used for determination cells proliferation, colony formation, and invasiveness. Western blotting assay was used for assessment of protein expression whereas AutoDock Vina and Discovery studio software for in silico studies. RESULTS: Tretinoin treatment significantly (p < .05) reduced the proliferation of HT-3 and Caski cells in concentration-based manner. Incubation with tretinoin caused a significant decrease in clonogenic survival of HT-3 and Caski cells compared with the control cultures. The invasive potential of HT-3 cells was decreased to 18%, whereas that of Caski cells to 21% on treatment with 8 µM concentration of tretinoin. In HT-3 cells, tretinoin treatment led to a prominent reduction in p-focal adhesion kinase (FAK), matrix metalloproteinases (MMP)-2, and MMP-9 expression in HT-3 cells. Treatment of the cervical cancer mice model with tretinoin led to a prominent decrease in tumor growth. The metastasis of tumor in model cervical cancer mice group was effectively inhibited in spleen, intestines, and peritoneal cavity. In silico studies showed that tretinoin interacts with alanine, proline, isoleucine, and glycine amino acid residues of FAK protein to block its activation. The 2-dimensional diagram of interaction of tretinoin with FAK protein revealed that tretinoin binds to alanine and glycine amino acids through conventional hydrogen bonding. CONCLUSION: In summary, tretinoin suppressed the proliferation, colony formation, and invasiveness of cervical cancer cells in vitro. It decreased the expression of activated focal adhesion kinase, MMP-2, and MMP-9 in HT-3 cells in dose-dependent manner. In silico studies showed that tretinoin interacts with alanine and glycine amino acids through conventional hydrogen bonding. In vivo data demonstrated that treatment of the cervical cancer mice model with tretinoin led to a prominent decrease in tumor growth. Therefore, tretinoin can be developed as an effective therapeutic agent for cervical cancer treatment.

Relationship of Lactobacillus Vaginal Microbiota Changes and the Risk of Preterm Birth: A Systematic Review and Meta-Analysis.

Objective: With a global incidence of more than 10%, preterm birth (PTB) remains a significant concern. The vaginal microbiome strongly influences the well-being of the female reproductive tract. This study examines the correlation between changes in Lactobacillus vaginal microbiota and the PTB risk. Materials and Methods: A thorough search of PubMed, Web of Science, Cochrane Library, and EMBASE was conducted to locate studies that examined the association between changes in Lactobacillus vaginal microbiota and the risk of PTB from January 1, 2010, to January 30, 2023. The risk of PTB was determined by calculating odds ratios (ORs) with 95% confidence intervals (CIs). Results: In our analysis, there were 11 studies with 1577 pregnant women. The findings revealed a significant negative correlation between higher Lactobacillus abundance and the PTB risk (OR = 0.49, 95% CI: 0.29-0.84, p = 0.009 < 0.05). Similarly, the four individual dominant species, Lactobacillus crispatus (OR = 0.3, 95% CI: 0.14-0.67, p = 0.003 < 0.05), Lactobacillus gasseri (OR = 0.34, 95% CI: 0.17-0.69, p = 0.003 < 0.05), Lactobacillus iners (OR = 0.68, 95% CI: 0.49-0.93, p = 0.016 < 0.05), and Lactobacillus jensenii (OR = 0.43, 95% CI: 0.21-0.89, p = 0.024 < 0.05), were also negatively associated with the PTB risk. The risk of Lactobacillus for PTB was significant in both America (OR = 0.67; 95% CI: 0.50-0.92) and Asia (OR = 0.20; 95% CI: 0.09-0.47), whereas no significant risk was found in Europe (OR = 0.49; 95% CI: 0.11-2.15). Conclusions: Our study demonstrated that the abundance of Lactobacillus and the four dominant individual species (L. crispatus, L. jensenii, L. iners, and L. gasseri) were significantly and negatively associated with the PTB risk.

Incidence, distribution, disease spectrum, and genetic deficits of congenital heart defects in China: implementation of prenatal ultrasound screening identified 18,171 affected fetuses from 2,452,249 pregnancies.

BACKGROUND: Congenital heart defects (CHDs) are the most common birth defects. Assessment of the incidence, distribution, disease spectrum, and genetic deficits of fetal CHDs in China is urgently needed. METHODS: A national echocardiography screening program for fetal CHDs was implemented in 92 prenatal screening-diagnostic centers in China. FINDINGS: A total of 18,171 fetal CHD cases were identified from 2,452,249 pregnancies, resulting in 7·4/1,000 as the national incidence rate of fetal CHD. The incidences of fetal CHD in the six geographical regions, the southern, central, eastern, southwestern, northern, and northwestern, were 7·647 (CI: 7·383-7·915), 7·839 (CI: 7·680-8·000), 7·647 (CI: 7·383-7·915), 7·562 (CI: 7·225-7·907), 5·618 (CI: 5·337-5·906), and 4·716 (CI: 4·341-5·108), respectively, per 1,000 pregnancies. Overall, ventricular septal defect was the most common fetal CHD, accounting for 17.04% of screened pregnancies nationwide, and tetralogy of Fallot, the most common anomaly in the major defect of fetal CHD, was the second most common, accounting for 9.72%. A total of 76.24% cases of fetal CHD were found to be an isolated intracardiac single defect. The remaining 23.76% of cases of fetal CHD had multiple heart defects. Among all extracardiac malformations, the central nervous system (CNS) was the most common tissue with extracardiac anomalies associated with CHD, accounting for 22.89% of fetal CHD cases. Chromosomal karyotyping identified trisomy 18 as the most common chromosomal abnormality in fetal CHD. We also documented that CHD-containing syndromes could be identified with a comprehensive approach integrating prenatal ultrasound, MRI, pathological autopsy, and cytogenetics and molecular genetics. CONCLUSION: Implementation of prenatal echocardiography as a practically feasible platform to screen fetal CHD will reduce the financial and emotional burden of CHD, which may facilitate intrauterine and neonatal intervention of CHD.

Integrated Three-Electrode Dual-Mode Detection Chip for Place Cell Analysis: Dopamine Facilitates the Role of Place Cells in Encoding Spatial Locations of Novel Environments and Rewards.

The functioning of place cells requires the involvement of multiple neurotransmitters, with dopamine playing a critical role in hippocampal place cell activity. However, the exact mechanisms through which dopamine influences place cell activity remain largely unknown. Herein, we present the development of the integrated three-electrode dual-mode detection chip (ITDDC), which enables simultaneous recording of the place cell activity and dopamine concentration fluctuation. The working electrode, reference electrode, and counter electrode are all integrated within the ITDDC in electrochemical detection, enabling the real-time in situ monitoring of dopamine concentrations in animals in motion. The reference, working, and counter electrodes are surface-modified using PtNPs and polypyrrole, PtNPs and PEDOT:PSS, and PtNPs, respectively. This modification allows for the detection of dopamine concentrations as low as 20 nM. We conducted dual-mode testing on mice in a novel environment and an environment with food rewards. We found distinct dopamine concentration variations along different paths within a novel environment, implying that different dopamine levels may contribute to spatial memory. Moreover, environmental food rewards elevate dopamine significantly, followed by the intense firing of reward place cells, suggesting a crucial role of dopamine in facilitating the encoding of reward-associated locations in animals. The real-time and in situ recording capabilities of ITDDC offer new opportunities to investigate the interplay between electrophysiology and dopamine during animal exploration and reward-based memory and provide a novel glimpse into the correlation between dopamine levels and place cell activity.

Cancer/testis-45A1 promotes cervical cancer cell tumorigenesis and drug resistance by activating oncogenic SRC and downstream signaling pathways.

BACKGROUND: Cancer/testis antigen-45A1 (CT45A1) is overexpressed in various types of cancer but is not expressed in healthy women. The role of CT45A1 in cervical cancer has not yet been described in the literature. PURPOSE: The aim of this research was to study the role of CT45A1 in cervical cancer progression and drug resistance, elucidate the mechanisms underlying CT45A1-mediated tumorigenesis and investigate CT45A1 as a biomarker for cervical cancer diagnosis, prognostic prediction, and targeted therapy. METHODS: The CT45A1 levels in the tumors from cervical cancer patients were measured using immunohistochemical staining. The role and mechanisms underlying CT45A1-mediated cervical cancer cell tumor growth, invasion, and drug resistance were studied using xenograft mice, cervical cancer cells, immunohistochemistry, RNA-seq, real-time qPCR, Chromatin immunoprecipitation and Western blotting. RESULTS: CT45A1 levels were notably high in the tumor tissues of human cervical cancer patients compared to the paracancerous tissues (p < 0.001). Overexpression of CT45A1 was closely associated with poor prognosis in cervical cancer patients. CT45A1 promoted cervical cancer cell tumor growth, invasion, neovascularization, and drug resistance. Mechanistically, CT45A1 promoted the expression of 128 pro-tumorigenic genes and concurrently activated key signaling pathways, including the oncogenic SRC, ERK, CREB, and YAP/TAZ signaling pathways. Furthermore, CT45A1-mediated tumorigenesis and drug resistance were markedly inhibited by the small molecule lycorine. CONCLUSION: CT45A1 promotes cervical cancer cell tumorigenesis, neovascularization, and drug resistance by activating oncogenic SRC and downstream tumorigenic signaling pathways. These findings provide new insight into the pathogenesis of cervical cancer and offer a new platform for the development of novel therapeutics against cervical cancer.

Protocol for transcriptome assembly by the TransBorrow algorithm.

High-throughput RNA-seq enables comprehensive analysis of the transcriptome for various purposes. However, this technology generally generates massive amounts of sequencing reads with a shorter read length. Consequently, fast, accurate, and flexible tools are needed for assembling raw RNA-seq data into full-length transcripts and quantifying their expression levels. In this protocol, we report TransBorrow, a novel transcriptome assembly software specifically designed for short RNA-seq reads. TransBorrow is employed in conjunction with a splice-aware alignment tool (e.g. Hisat2 and Star) and some other transcriptome assembly tools (e.g. StringTie, Cufflinks, and Scallop). The protocol encompasses all necessary steps, starting from downloading and processing raw sequencing data to assembling the full-length transcripts and quantifying their expressed abundances. The execution time of the protocol may vary depending on the sizes of processed datasets and computational platforms.

Recent advances and research progress on microsystems and bioeffects of terahertz neuromodulation.

Terahertz waves can interact with the nervous system of organisms under certain conditions. Compared to common optical modulation methods, terahertz waves have the advantages of low photon energy and low risk; therefore, the use of terahertz waves to regulate the nervous system is a promising new method of neuromodulation. However, most of the research has focused on the use of terahertz technology for biodetection, while relatively little research has been carried out on the biological effects of terahertz radiation on the nervous system, and there are almost no review papers on this topic. In the present article, we begin by reviewing principles and objects of research regarding the biological effects of terahertz radiation and summarizing the current state of related research from a variety of aspects, including the bioeffects of terahertz radiation on neurons in vivo and in vitro, novel regulation and detection methods with terahertz radiation devices and neural microelectrode arrays, and theoretical simulations of neural information encoding and decoding. In addition, we discuss the main problems and their possible causes and give some recommendations on possible future breakthroughs. This paper will provide insight and assistance to researchers in the fields of neuroscience, terahertz technology and biomedicine.

Nonreducing Ambient Atmosphere: Pulsed Electric Current Treatment of Co/Ni Doped Perovskite Oxides to Achieve Exsolution Enhanced Electrochemical Performance.

Exsolution of metal nanoparticles (NPs) on the surface of perovskite oxides is a promising approach for developing advanced catalytic materials through a "bottom-up" design strategy. Under a nonreducing ambient atmosphere utilizing pulsed electric current (PEC) treatment to promote the exsolution of perovskite oxides effectively overcomes the limitations inherent in conventional high-temperature vapor phase reduction (HTVPR) in situ exsolution methods. This paper presents the successful synthesis of (La0.7Sr0.3)0.8Ti0.93Ni0.07O3 (LSTN) perovskite oxide and (La0.7Sr0.3)0.8Ti0.93Co0.07O3 (LSTC) perovskite oxide using the sol-gel method, followed by PEC treatment at 600 V, 3 Hz, and 90 s. Utilizing various characterization techniques to confirm that PEC treatment can promote the exsolution of Co and Ni NPs under a nonreducing ambient atmosphere, the results indicated that the exsolved perovskite oxides exhibited significantly improved electrochemical properties. Furthermore, compared to the LSTN-PEC, LSTC-PEC demonstrates a lower onset potential of 1.504 V, a Tafel slope of 87.16 mV dec-1, lower impedance, higher capacitance, superior catalytic activity, and long-term stability.

2022 Chinese guideline for the management of pregnancy and reproduction in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE), a prevalent autoimmune disease predominantly affecting women of childbearing age, presents ongoing challenges despite notable advances in diagnosis and treatment. Although survival rates for SLE patients have significantly improved, pregnancy continues to pose a considerable obstacle. Addressing this critical need for enhanced reproductive and prenatal care, there is a pressing imperative to establish standardized protocols for peri-gestational monitoring and treatment in SLE patients. This guideline is jointly sponsored by the National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), the Chinese Systemic Lupus Erythematosus Treatment and Research Group (CSTAR), and the Chinese Research Committee of Pregnancy and Reproduction in Autoimmune Rheumatic Diseases (CHOPARD). Thirteen pertinent clinical questions have been generated through several rounds of rigorous clinical and methodological expert discussions and selections for a comprehensive understanding of key aspects in this domain. Guided by thorough examination of research evidence and expert perspectives, the formulated recommendations aim to optimize pregnancy success rates, reduce maternal and infant mortality rates, and ultimately enhance the overall well-being of SLE patients.

Spatom: a graph neural network for structure-based protein-protein interaction site prediction.

Accurate identification of protein-protein interaction (PPI) sites remains a computational challenge. We propose Spatom, a novel framework for PPI site prediction. This framework first defines a weighted digraph for a protein structure to precisely characterize the spatial contacts of residues, then performs a weighted digraph convolution to aggregate both spatial local and global information and finally adds an improved graph attention layer to drive the predicted sites to form more continuous region(s). Spatom was tested on a diverse set of challenging protein-protein complexes and demonstrated the best performance among all the compared methods. Furthermore, when tested on multiple popular proteins in a case study, Spatom clearly identifies the interaction interfaces and captures the majority of hotspots. Spatom is expected to contribute to the understanding of protein interactions and drug designs targeting protein binding.

Cluster analysis of antiphospholipid antibodies-associated adverse pregnancy outcome patients: based on a 13-years cohort study.

Antiphospholipid antibodies (aPLs) are the leading causes of adverse pregnancy outcomes (APOs). We conducted cluster analysis to identify distinct phenotypes among aPLs-associated APOs patients. This approach aims to facilitate risk stratification and improve pregnancy outcomes for obstetric APS. This was a retrospective study of persistent aPLs positive women cohort in Peking Union Medical College Hospital. Baseline demographic characteristics, clinical manifestation, previous APOs and antibodies profiles were included for hierarchical cluster analysis. Placentae from portions of patients were collected and performed the histopathologic diagnoses. Four clusters among 209 patients with 477 pregnancies were identified. Cluster 1 comprised patients with triple aPLs positivity and demonstrates a high incidence of gestational hypertension (34.92%, P < 0.05) and preterm delivery (20.63%, P < 0.05). Patients in cluster 2 were characterized by lupus anticoagulant (LA) positivity, with high risk of whole gestational APOs. Cluster 3 included patients with isolated aPLs-IgM isotype combined with early miscarriage (60.92%, P = 0.016). Patients in cluster 4 majorly presented aPLs-IgG isotype combined with placenta insufficiency (22.73%). During the follow-up, the live birth rate in cluster 1 and 2 was only 69.20%. Placenta pathology revealed the most severe impairment within cluster 1, whereas clusters 3 and 4 exhibited relatively milder damage. By cluster analysis, we identified four clinical subtypes of aPLs-associated APOs patients. Patients with triple antibodies or high-risk lupus characteristics were prone to occurred gestational hypertension and premature delivery. Isolated LA or aCL/aß2GPI positivity were found to be more frequently associated with early-stage fetal loss.

Protocol for predicting peptides with anticancer and antimicrobial properties by a tri-fusion neural network.

Here, we describe the use of TriNet to predict peptides with anticancer and antimicrobial properties by a tri-fusion neural network. We detail the use of TriNet for both the offline Python script version and the online service, thereby demonstrating its convenience for users. In addition, we provide a detailed explanation of the training process of TriNet to enhance the understanding of researchers seeking to leverage deep learning techniques for peptide classification. For complete details on the use and execution of this protocol, please refer to Zhou et al.1.

Impaired Spatial Firing Representations of Neurons in the Medial Entorhinal Cortex of the Epileptic Rat Using Microelectrode Arrays.

Epilepsy severely impairs the cognitive behavior of patients. It remains unclear whether epilepsy-induced cognitive impairment is associated with neuronal activities in the medial entorhinal cortex (MEC), a region known for its involvement in spatial cognition. To explore this neural mechanism, we recorded the spikes and local field potentials from MEC neurons in lithium-pilocarpine-induced epileptic rats using self-designed microelectrode arrays. Through the open field test, we identified spatial cells exhibiting spatially selective firing properties and assessed their spatial representations in relation to the progression of epilepsy. Meanwhile, we analyzed theta oscillations and theta modulation in both excitatory and inhibitory neurons. Furthermore, we used a novel object recognition test to evaluate changes in spatial cognitive ability of epileptic rats. After the epilepsy modeling, the spatial tuning of various types of spatial cells had suffered a rapid and pronounced damage during the latent period (1 to 5 d). Subsequently, the firing characteristics and theta oscillations were impaired. In the chronic period (>10 d), the performance in the novel object experiment deteriorated. In conclusion, our study demonstrates the detrimental effect on spatial representations and electrophysiological properties of MEC neurons in the epileptic latency, suggesting the potential use of these changes as a "functional biomarker" for predicting cognitive impairment caused by epilepsy.

Antibacterial Polyketides Isolated from the Marine-Derived Fungus Fusarium solani 8388.

Seven new polyketides named fusarisolins F-K (1-6) and fusarin I (7) were isolated from the marine-derived fungus Fusarium solani 8388, together with the known anhydrojavanicin (8), 5-deoxybostry coidin (9), and scytalol A (10). Their structures were established by comprehensive spectroscopic data analyses, and by comparison of the 1H and 13C NMR data with those reported in literature. Fusarisolin F (1) contained both a dichlorobenzene group and an ethylene oxide unit, which was rare in nature. In the bioassays, fusarisolin I (4), fusarisolin J (5), and 5-deoxybostry coidin (9) exhibited obvious antibacterial activities against methicillin-resistant Staphylococcus aureus n315 with MIC values of 3, 3, and 6 µg/mL, respectively. Fusarisolin H (3) and fusarisolin J (5) showed inhibitory effects against methicillin-resistant Staphylococcus aureus NCTC 10442 with the same MIC value of 6 µg/mL. With the exception of 5, all other compounds did not show or showed weak cytotoxicities against HeLa, A549, and KB cells; while fusarisolin J (5) demonstrated moderate cytotoxicities against the three human cancer cell lines with CC50 values between 9.21 and 14.02 µM.

Lycorine inhibits pancreatic cancer cell growth and neovascularization by inducing Notch1 degradation and downregulating key vasculogenic genes.

Pancreatic cancer is highly metastatic and lethal with an increasing incidence globally and a 5-year survival rate of only 8%. One of the factors contributing to the high mortality is the lack of effective drugs in the clinical setting. We speculated that effective compounds against pancreatic cancer exist in natural herbs and explored active small molecules among traditional Chinese medicinal herbs. The small molecule lycorine (MW: 323.77) derived from the herb Lycoris radiata inhibited pancreatic cancer cell growth with an IC50 value of 1 µM in a concentration-dependent manner. Lycorine markedly reduced pancreatic cancer cell viability, migration, invasion, neovascularization, and gemcitabine resistance. Additionally, lycorine effectively suppressed tumor growth in mouse xenograft models without obvious toxicity. Pharmacological studies revealed that the levels and half-life of Notch1 oncoprotein in the pancreatic cancer cells Panc-1 and Patu8988 were notably reduced. Moreover, the expression of the key vasculogenic genes Semaphorin 4D (Sema4D) and angiopoietin-2 (Ang-2) were also significantly inhibited by lycorine. Mechanistically, lycorine strongly triggered the degradation of Notch1 oncoprotein through the ubiquitin-proteasome system. In conclusion, lycorine effectively inhibits pancreatic cancer cell growth, migration, invasion, neovascularization, and gemcitabine resistance by inducing degradation of Notch1 oncoprotein and downregulating the key vasculogenic genes Sema4D and Ang-2. Our findings provide a new therapeutic candidate and treatment strategy against pancreatic cancer.