Spatiotemporal lineage tracing reveals the dynamic spatial architecture of tumor growth and metastasis.

Tumor progression is driven by dynamic interactions between cancer cells and their surrounding microenvironment. Investigating the spatiotemporal evolution of tumors can provide crucial insights into how intrinsic changes within cancer cells and extrinsic alterations in the microenvironment cooperate to drive different stages of tumor progression. Here, we integrate high-resolution spatial transcriptomics and evolving lineage tracing technologies to elucidate how tumor expansion, plasticity, and metastasis co-evolve with microenvironmental remodeling in a Kras;p53 -driven mouse model of lung adenocarcinoma. We find that rapid tumor expansion contributes to a hypoxic, immunosuppressive, and fibrotic microenvironment that is associated with the emergence of pro-metastatic cancer cell states. Furthermore, metastases arise from spatially-confined subclones of primary tumors and remodel the distant metastatic niche into a fibrotic, collagen-rich microenvironment. Together, we present a comprehensive dataset integrating spatial assays and lineage tracing to elucidate how sequential changes in cancer cell state and microenvironmental structures cooperate to promote tumor progression.

Prognostic value of multi-PLD ASL-based cerebral perfusion ASPECTS in acute ischemic stroke.

Introduction: We aimed to verify the application value of the Alberta Stroke Program Early CT Score (ASPECTS) based on multiple post-labeling delay (multi-PLD) arterial spin labeling (ASL) for outcome assessment in acute ischemic stroke (AIS) patients. Method: The endpoint was modified Rankin scale score at 90 days (90-day mRS). Patients were divided into the good outcome (0-2) and poor outcome (3-6) groups. The independent samples t-test, Mann-Whitney U-test, and χ2-test were used to compare clinical and imaging parameters between groups. We used partial correlation analysis to evaluate the relationships between ASPECTS and outcomes. Multivariate logistic regression analysis was used to examine potential independent prognostic indicators. The receiver operating characteristic (ROC) curve analysis was used to evaluate the performance of the independent prognostic indicators in predicting outcomes. Results: Fifty-five AIS patients were included. The good outcome group had a lower baseline National Institutes of Health Stroke Scale (NIHSS; Z = -3.413, P < 0.001) and infarct core volume (ICV; Z = -3.114, P = 0.002) as well as higher cerebral blood flow (CBF)-ASPECTS (Z = -3.835, P < 0.001) and cerebral blood volume (CBV)-ASPECTS (Z = -4.099, P < 0.001). Higher CBF-ASPECTS (r = -0.459, P = 0.001), and CBV-ASPECTS (r = -0.502, P < 0.001) were associated with a lower 90-day mRS. The baseline NIHSS, CBF-ASPECTS, and CBV-ASPECTS were identified as independent prognostic indicators. The AUCs of the baseline NIHSS, CBF-ASPECTS, and CBV-ASPECTS were 83.3, 87.4, and 89.9%, respectively. Combining NIHSS with CBF-ASPECTS and CBV-ASPECTS, the AUC significantly improved to 96.3%. The combined three factors showed a significant difference compared to the baseline NIHSS (Z = 2.039, P = 0.041) and CBF-ASPECTS (Z = 2.099, P = 0.036), but no difference with CBV-ASPECTS (Z = 1.176, P = 0.239). Conclusions: The ASPECTS based on multi-PLD ASL is a valuable tool for identifying independent prognostic indicators and assessing clinical outcomes in AIS patients. The baseline NIHSS, combined with CBF-ASPECTS and CBV-ASPECTS, enhances the predictive efficacy of clinical outcomes in AIS patients. The CBV-ASPECTS alone can offer comparable predictive efficacy to the combination.

Concurrent activation of CO2 and H2O on sulfur-doped CNT-supported nickel phthalocyanine for electrochemical CO2 reduction to CO.

Concurrent activation of CO2 and H2O is essential for CO2 electroreduction reaction, but challenging. A sulfur-doped carbon nanotubes-supported nickel phthalocyanine (NiPc/S-CNTs) can concurrently activate CO2 and H2O, promoting CO2 protonation to *COOH. The NiPc/S-CNTs achieves CO Faraday efficiency of >96% at current density from -20 to -140 mA cm-2.

Expansion in situ genome sequencing links nuclear abnormalities to hotspots of aberrant euchromatin repression.

Microscopy and genomics are both used to characterize cell function, but approaches to connect the two types of information are lacking, particularly at subnuclear resolution. While emerging multiplexed imaging methods can simultaneously localize genomic regions and nuclear proteins, their ability to accurately measure DNA-protein interactions is constrained by the diffraction limit of optical microscopy. Here, we describe expansion in situ genome sequencing (ExIGS), a technology that enables sequencing of genomic DNA and superresolution localization of nuclear proteins in single cells. We applied ExIGS to fibroblast cells derived from an individual with Hutchinson-Gilford progeria syndrome to characterize how variation in nuclear morphology affects spatial chromatin organization. Using this data, we discovered that lamin abnormalities are linked to hotspots of aberrant euchromatin repression that may erode cell identity. Further, we show that lamin abnormalities heterogeneously increase the repressive environment of the nucleus in tissues and aged cells. These results demonstrate that ExIGS may serve as a generalizable platform for connecting nuclear abnormalities to changes in gene regulation across disease contexts.

Causal relationship between oral microbiota and epilepsy risk: Evidence from Mendelian randomization analysis in East Asians.

OBJECTIVE: Gut microbiota can traverse into the brain, activate the vagus nerve, and modulate immune responses and inflammatory processes, thereby influencing the onset of epileptic seizures. However, research on oral microbiota and epilepsy remains limited, and observational studies have been inconsistent. We aim to estimate the potential links between oral microbiota and epilepsy and elucidate which specific oral microbes may directly influence the pathogenesis of epilepsy. METHODS: A two-sample MR analysis was conducted using genome-wide association study (GWAS) data specific to OM and epilepsy in East Asian individuals. Single nucleotide polymorphisms (SNPs) independent of confounders served as instrumental variables (IVs) to deduce causality. MR methodologies, including inverse variance weighted (IVW), MR-Egger, weighted median, and weighed mode methods, were utilized. Sensitivity analysis, including Cochrane's Q test, MR-Egger intercept test, and leave-one-out analysis, was applied to confirm the robustness of results. RESULTS: Among the 3117 bacterial taxa examined, we observed that 14 OM, like s_Streptococcus_mitis, s_Streptococcus_pneumoniae, and s_Haemophilus, were positively associated with epilepsy, while 7 OM, like g_Fusobacterium and g_Aggregatibacter, were negatively related to epilepsy. The MR-Egger intercept suggested that no evidence of horizontal pleiotropy was observed (p > 0.05). The leave-one-out analysis validated the robustness of the results. SIGNIFICANCE: This study underscores the effect of OM on epilepsy, suggesting potential mechanisms between the OM and epilepsy. Further investigation into the potential role of the OM is needed to enhance our in-depth understanding of the pathogenesis of epilepsy. PLAIN LANGUAGE SUMMARY: Previous research has demonstrated that the microbiota may influence the onset of epileptic seizures. We applied 3117 oral microbiota from the newest publicly available database of East Asian populations. Mendelian randomization analysis was utilized to estimate the causal relationship between oral microbiota and epilepsy. Our results showed that a causal effect exists between 21 oral microbiota and epilepsy. We provided genetic evidence for risk assessment and early intervention in epilepsy.

AI-driven precision subcellular navigation with fluorescent probes.

Precise navigation within intricate biological systems is pivotal for comprehending cellular functions and diagnosing diseases. Fluorescent molecular probes, designed to target specific biological molecules, are indispensable tools for this endeavor. This paper delves into the revolutionary potential of artificial intelligence (AI) in crafting highly precise and effective fluorescent probes. We will discuss how AI can be employed to: design new subcellular dyes by optimizing physicochemical properties; design prospective subcellular targeting probes based on specific receptors; quantitatively explore the potential chemical laws of fluorescent molecules to optimize the optical properties of fluorescent probes; optimize the comprehensive properties of the probe and guide the construction of multifunctional targeting probes. Additionally, we showcase recent AI-driven advancements in probe development and their successful biomedical applications, while addressing challenges and outlining future directions towards transforming subcellular research, diagnostics, and drug discovery.

Identification of oxylipins and lipid mediators in pulmonary embolism.

BACKGROUND: This study aimed to investigate the role of oxylipins and lipid mediators in Pulmonary Embolism (PE), a serious cardiovascular condition associated with high morbidity and mortality rates. METHODS: A total of 6,365 hospitalized patients with thrombosis and 200 healthy individuals were recruited as the control group from 2015 to 2023. Thrombus type, coagulation, and lipid-related parameters were statistically analysed. Additionally, lipidomic characteristics of serum samples from the PE and control groups were examined via LC-MS/MS for the first time. RESULTS: Among the 6,365 hospitalized patients with thrombosis, 72.1% (4,587/6,365) had venous thromboembolism (VTE). Within the VTE group, the incidence of PE was 12.1% (555/4,587). In comparison to the healthy control (HC) group, the PE group exhibited significant elevations in coagulation-related parameters, such as factor VIII (F VIII) and von Willebrand factor (vWF) activities, while antithrombin III (AT III) and factor XII (F XII) activities were notably reduced. Lipid-related parameters, including serum cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A (apoA), were significant reductions in PE patients (P < 0.0001), with areas under the curve (AUCs) exceeding 0.9. LC-MS/MS analysis of serum samples revealed 118 oxidized lipid metabolites. Compared to the HC group, the PE group exhibited 10 upregulated oxidized lipid metabolites, with the most significant difference observed in 20-hydroxyPGF2α derived from arachidonic acid (ARA). The study identified upregulated oxidized lipid metabolites primarily linked to the ARA metabolism signalling pathway. CONCLUSION: This research indicates a notable correlation between lipid metabolism and the occurrence and development of PE. Specifically, upregulation of the arachidonic acid metabolism signalling pathway may be an important pathogenic factor for PE, and 20-hydroxyPGF2α derived from ARA has potential as a biomarker for PE disease.

Assessing the feasibility of ChatGPT-4o and Claude 3-Opus in thyroid nodule classification based on ultrasound images.

PURPOSE: Large language models (LLMs) are pivotal in artificial intelligence, demonstrating advanced capabilities in natural language understanding and multimodal interactions, with significant potential in medical applications. This study explores the feasibility and efficacy of LLMs, specifically ChatGPT-4o and Claude 3-Opus, in classifying thyroid nodules using ultrasound images. METHODS: This study included 112 patients with a total of 116 thyroid nodules, comprising 75 benign and 41 malignant cases. Ultrasound images of these nodules were analyzed using ChatGPT-4o and Claude 3-Opus to diagnose the benign or malignant nature of the nodules. An independent evaluation by a junior radiologist was also conducted. Diagnostic performance was assessed using Cohen's Kappa and receiver operating characteristic (ROC) curve analysis, referencing pathological diagnoses. RESULTS: ChatGPT-4o demonstrated poor agreement with pathological results (Kappa = 0.116), while Claude 3-Opus showed even lower agreement (Kappa = 0.034). The junior radiologist exhibited moderate agreement (Kappa = 0.450). ChatGPT-4o achieved an area under the ROC curve (AUC) of 57.0% (95% CI: 48.6-65.5%), slightly outperforming Claude 3-Opus (AUC of 52.0%, 95% CI: 43.2-60.9%). In contrast, the junior radiologist achieved a significantly higher AUC of 72.4% (95% CI: 63.7-81.1%). The unnecessary biopsy rates were 41.4% for ChatGPT-4o, 43.1% for Claude 3-Opus, and 12.1% for the junior radiologist. CONCLUSION: While LLMs such as ChatGPT-4o and Claude 3-Opus show promise for future applications in medical imaging, their current use in clinical diagnostics should be approached cautiously due to their limited accuracy.

Efficient conversion of hemicellulose into high-value product and electric power by enzyme-engineered bacterial consortia.

As an abundant agricultural and forestry biomass resource, hemicelluloses are hard to be effectively degraded and utilized by microorganisms due to the constraints of membrane and metabolic regulations. Herein, we report a synthetic extracellular metabolic pathway with hemicellulose-degrading-enzymes controllably displayed on Escherichia coli surface as engineered bacterial consortia members for efficient utilization of xylan, the most abundant component in hemicellulose. Further, we develop a hemicellulose/O2 microbial fuel cell (MFC) configuring of enzyme-engineered bacterial consortia based bioanode and bacterial-displayed laccase based biocathode. The optimized MFC exhibited an open-circuit voltage of 0.71 V and a maximum power density (Pmax) of 174.33 ± 4.56 µW cm-2. Meanwhile, 46.6% (w/w) α-ketoglutarate was produced in this hemicellulose fed-MFC. Besides, the MFC retained over 95% of the Pmax during 6 days' operation. Therefore, this work establishes an effective and sustainable one-pot process for catalyzing renewable biomass into high-value products and electricity in an environmentally-friendly way.

Inflammatory cytokines and carpal tunnel syndrome: A causal relationship revealed.

OBJECTIVES: Carpal tunnel syndrome (CTS) and certain inflammatory cytokines have been linked in observational studies; however, the exact causative linkages remain unknown. The purpose of this study is to investigate any possible link between the onset of CTS and 91 inflammatory cytokines. METHODS: A two-sample bidirectional Mendelian randomization (MR) approach was used in this investigation. 91 circulating inflammatory cytokines' genetic variants were retrieved from the European ancestry genome-wide association study (GWAS) database. From germline GWAS, summary data for 24,766 CTS patients and 360,538 controls were gathered. The instrumental variables were single nucleotide polymorphisms (SNPs) that were highly correlated with the 91 inflammatory cytokines. The random-effects inverse-variance weighted (IVW) approach was employed in the primary analysis, and multiple comparisons were subjected to the Bonferroni correction. Sensitivity analysis was performed to evaluate the validity of the causal relationship. RESULTS: Our findings showed a negative correlation between CCL19, FGF-19, IL-5, TGF-alpha, TRAIL, and the risk of CTS. Specifically, CCL19 (odds ratio [OR]: 0.944, 95 % confidence interval [CI]: 0.894-0.996, p = 0.0349), FGF-19 (OR: 0.940, 95 % CI: 0.894-0.987, p = 0.0133), IL-5 (OR: 0.936, 95 % CI: 0.885-0.990, p = 0.0212), TGF-alpha (OR: 0.902, 95 % CI: 0.838-0.970, p = 0.0057), and TRAIL (OR: 0.926, 95 % CI: 0.881-0.974, p = 0.0026) were inversely related to CTS risk. Conversely, CCL20, IL-2RB, and IL-6 were positively associated with an increased risk of CTS. Specifically, CCL20 (OR: 1.072, 95 % CI: 1.005-1.142, p = 0.0334), IL-2RB (OR: 1.067, 95 % CI: 1.001-1.137, p = 0.0463), and IL-6 (OR: 1.088, 95 % CI: 1.005-1.177, p = 0.0365) were positively correlated with CTS risk. Reverse Mendelian randomization analyses indicated no evidence of a reverse causal relationship between CTS and inflammatory cytokines. CONCLUSION: According to this study, there is a causal link between CTS and certain inflammatory cytokines, which suggests that these cytokines may be important in the pathophysiology of CTS. To confirm these results and investigate the specific function of these cytokines in the beginning and development of CTS, more investigation is necessary.

Helicase-assisted continuous editing for programmable mutagenesis of endogenous genomes.

Deciphering the context-specific relationship between sequence and function is a major challenge in genomics. Existing tools for inducing locus-specific hypermutation and evolution in the native genome context are limited. Here we present a programmable platform for long-range, locus-specific hypermutation called helicase-assisted continuous editing (HACE). HACE leverages CRISPR-Cas9 to target a processive helicase-deaminase fusion that incurs mutations across large (>1000-base pair) genomic intervals. We applied HACE to identify mutations in mitogen-activated protein kinase kinase 1 (MEK1) that confer kinase inhibitor resistance, to dissect the impact of individual variants in splicing factor 3B subunit 1 (SF3B1)-dependent missplicing, and to evaluate noncoding variants in a stimulation-dependent immune enhancer of CD69. HACE provides a powerful tool for investigating coding and noncoding variants, uncovering combinatorial sequence-to-function relationships, and evolving new biological functions.

PXDN as a pan-cancer biomarker and promotes tumor progress via immune inhibition in nasopharyngeal carcinoma.

Background: Investigating oncogenes and the mechanisms driving oncogenic processes in human tumors is imperative for the development of efficient therapies. Peroxidasin (PXDN) has been reported to play a critical role in tissue development and homeostasis. However, the role of PXDN in the occurrence and development of Nasopharyngeal Carcinoma (NPC) remains unknown. Methods: Data from multiple databases, including GEO and TCGA, were used to analyze the expression levels of PXDN. Taking nasopharyngeal carcinoma as an example, in vitro experiments were conducted to explore the biological functions of PXDN. Overexpression of stable cell lines was achieved through lentiviral infection, cell proliferation was examined using CCK8 and BrdU incorporation assays, and clone formation experiments were performed to assess cell growth. Transwell and wound healing assays were employed to evaluate cell invasion and migration abilities. Additionally, immunofluorescence staining with multiple targets was used to analyze the immune microenvironment of the tumor tissues. Co-culture experiments, followed by clone formation and CFSE incorporation assays, were conducted to observe the impact of NPC stable cell lines on T cells. Flow cytometry was performed to detect surface markers and cytokines in T cells after co-culture to assess T cell function. Results: PXDN was highly expressed in multiple tumors, and its high expression and mutation profile were correlated with poor survival. Functionally, PXDN plays a crucial role in promoting oncogenic processes by enhancing NPC cell proliferation and metastasis. Mechanistically, PXDN activates extracellular matrix (ECM) signaling pathways while simultaneously inhibiting T-cell infiltration and activation, thereby facilitating cancer progression. Conclusion: We characterized PXDN as a valuable biomarker for pan-cancer diagnosis and prognosis. We also uncovered new oncogenic roles for PXDN in promoting cancer progression and regulating T-cell immunosuppressive function in NPC.

Monoterpene indole glycoalkaloids from the hook-bearing branches of Uncaria rhynchophylla.

Twelve monoterpene indole glycoalkaloids, comprising of three new ones, 19-epi-rhynchophylloside A (1), 7-epi-rhynchophylloside A (2), and 7-epi-anthocephalusine A (3), were isolated from the hook-bearing branches of Uncaria rhynchophylla. The structures and absolute configurations of 1-3 were elucidated by analysis of MS, NMR, ECD, and single-crystal X-ray diffraction or TDDFT-ECD calculations. Glycoalkaloids 1 and 3 showed significant immunosuppressive activity against the proliferation of B lymphocyte induced by LPS with broad selective index.

Biomechanical effects of mandibular deviation on the temporomandibular joint in patients with mandibular prognathism under incisal occlusion.

PURPOSE: The aim of this study was to investigate the biomechanical effects of mandibular deviation on the TMJ in patients with mandibular prognathism before and after orthognathic surgery using three-dimensional finite element analysis. METHODS: Eight patients with mandibular prognathism without deviation, eight patients with mandibular prognathism with deviation and sixteen normal subjects were recruited. Three-dimensional models of the maxillofacial were reconstructed using MIMICS. Nine muscle forces were used to simulate incisal occlusion and contact was used to simulate fossa-disc-condyle interactions. RESULTS: Before surgery, the stress in the TMJ was generally greater in the Pre-MD&MP group than in the Pre-MD group; it was much greater in both groups than in the control group, ranging from about 2 to 12 times as great in the Pre-MD group and from about 5 to 64 times as great in the Pre-MD&MP group. After orthognathic surgeries, the stresses in the Post-MP&MD were significantly reduced by approximately 21.7 % to 93.4 %. And in the Post-MP group, the stresses were reduced by approximately 1.4 % to 51.1 %. CONCLUSION: Mandibular deviation exacerbated the abnormal stress distribution in the TMJ of patients with mandibular prognathism. Orthognathic surgeries could improve the stress distribution in patients with mandibular prognathism (with and without deviation). TMD was closely related to the stress levels of the TMJ.

Interaction between the oxidative balance score and serum per- and poly-fluoroalkyl substances (PFASs) on liver health: analysis of the NHANES 2007-2018 dataset.

BACKGROUND: Per- and poly-fluoroalkyl substances (PFASs) are pervasive synthetic compounds, prompting investigations into their intricate interactions with lifestyle factors and health indicators because of their enduring environmental presence and bioaccumulation. This study aimed to explore the effects of the oxidative balance score (OBS) and PFAS on liver-related indices. METHODS: Twenty dietary and lifestyle factors were used to calculate the OBS. The serum concentrations of PFASs were measured, and their sum was calculated for analysis. The levels of liver markers were also evaluated. Linear regression models and interaction analyses were used to assess the associations between OBS, PFAS concentrations, and liver indices. RESULTS: The results revealed an inverse association between high OBS and perfluorooctane sulfonic acid concentration, as well as the sum of PFAS concentrations. OBS was positively associated with liver markers. The PFAS concentrations were positively associated with total bilirubin, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) levels. Interaction analyses revealed significant interactions between OBS and specific PFASs for alkaline phosphatase (interaction P < 0.05). Possible interactions were also found between OBS and specific PFASs for ALT, and AST levels (interaction P < 0.10). CONCLUSIONS: This study clarified the association between total PFAS and OBS. This association was significant mainly for diet-related OBS. PFAS and OBS are associated with liver-related indicators in the blood.

A time series algorithm to predict surgery in neonatal necrotizing enterocolitis.

BACKGROUND: Determining the optimal timing of surgical intervention for Neonatal necrotizing enterocolitis (NEC) poses significant challenges. This study develops a predictive model using the long short-term memory network (LSTM) with a focal loss (FL) to identify infants at risk of developing Bell IIB + NEC early and issue timely surgical warnings. METHODS: Data from 791 neonates diagnosed with NEC are gathered from the Neonatal Intensive Care Unit (NICU), encompassing 35 selected features. Infants are categorized into those requiring surgical intervention (n = 257) and those managed medically (n = 534) based on the Mod-Bell criteria. A fivefold cross-validation approach is employed for training and testing. The LSTM algorithm is utilized to capture and utilize temporal relationships in the dataset, with FL employed as a loss function to address class imbalance. Model performance metrics include precision, recall, F1 score, and average precision (AP). RESULTS: The model tested on a real dataset demonstrated high performance. Predicting surgical risk 1 day in advance achieved precision (0.913 ± 0.034), recall (0.841 ± 0.053), F1 score (0.874 ± 0.029), and AP (0.917 ± 0.025). The 2-days-in-advance predictions yielded (0.905 ± 0.036), recall (0.815 ± 0.057), F1 score (0.857 ± 0.035), and AP (0.905 ± 0.029). CONCLUSION: The LSTM model with FL exhibits high precision and recall in forecasting the need for surgical intervention 1 or 2 days ahead. This predictive capability holds promise for enhancing infants' outcomes by facilitating timely clinical decisions.

AURKA inhibition shows promise as a therapeutic strategy for ARID1A-mutant colorectal cancer.

PURPOSE: Mutations in ARID1A frequently occur in colorectal cancer (CRC) cells. However, there are currently no clinical treatment options specifically addressing this aberration. The preliminary in vitro experiments revealed a synthetic lethal interaction between ARID1A and Aurora kinase A (AURKA) in colorectal cancer (CRC) cells. METHODS: We collected samples from 80 CRC patients and evaluated the efficacy of AURKA inhibitor (AURKAi) using the ATP-tumor chemosensitivity assay (ATP-TCA) on untreated ARID1A-proficient (ARID1A +) and ARID1A-deficient (ARID1A-) CRC patient samples. In addition, we validated this result by a clonogenic assay. Additionally, we examined the effects of AURKA inhibitors on cell cycle progression and apoptosis in ARID1A + and ARID1A- CRC patient samples using flow cytometry. RESULTS: The results showed that AURKAi selectively inhibited the growth of ARID1A- CRC cells. Furthermore, AURKA inhibitors significantly increased G2/M arrest and induced apoptosis in ARID1A- cells. CONCLUSION: We believe that AURKAi hold promise as potential therapeutics for ARID1A mutation colorectal cancer patients.

Three novel sesquiterpene polyol esters from the root bark of Celastrus angulatus Maxim and their nitric oxide inhibitory activity.

Three new sesquiterpene polyol ester compounds angulatin V [1ß,15-diacetoxy-2ß-(α-methyl)-butanoyloxy-4α,6α-dihydroxy-8α-isobutanoyloxy-9ß-benzoxy-ß-dihydroagarofuran], angulatin W [1ß,2ß-diacetoxy-4α,6α-dihydroxy-8-carbonyl-9ß-benzoxy-15-isobutanoyloxy-ß-dihydroagarofuran], angulatin X [1ß,2ß,8α-triacetoxy-4α, 6α-dihydroxy-9ß-benzoxy-15-nicotinyl-ß-dihydroagarofuran] (1-3), together with one known compound Putterine B (4), were isolated from the root bark of Celastrus angulatus Maxim. The structures of compounds 1-3 were elucidated by NMR, HRESIMS, IR data, and comparison with the literature data. The anti-inflammatory activity of all compounds was evaluated by measuring nitric oxide production in RAW264.7 macrophages. Compounds 1-4 showed no significant nitric oxide inhibitory activity at 2.5 and 5 µM concentrations.

Thoracic Radiotherapy Improves the Survival in Patients With EGFR-Mutated Oligo-Organ Metastatic Non-Small Cell Lung Cancer Treated With Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors: A Multicenter, Randomized, Controlled, Phase III Trial.

PURPOSE: This multicenter, randomized, phase III clinical trial (Northern Radiation Oncology Group of China-002) focused on patients with oligo-organ metastatic non-small cell lung cancer (NSCLC) who have epidermal growth factor receptor (EGFR) mutations. We aimed to investigate whether first-line concurrent thoracic radiotherapy (TRT) and EGFR-tyrosine kinase inhibitors (TKIs), compared with TKIs alone, could achieve better survival. MATERIALS AND METHODS: The patients in the TKI plus TRT group received 60 Gy to primary lung tumor and positive regional lymph nodes. Radiotherapy for metastases to other sites was determined by clinicians. The primary end point was the progression-free survival (PFS). Secondary end points included overall survival (OS) and treatment-related adverse events (TRAEs). The first and second interim analyses were performed in March 2021 and March 2022. RESULTS: Between April 14, 2016, and February 25, 2022, a total of 118 patients were enrolled. Compared with the TKI alone group, the TKI plus TRT group achieved significantly better PFS (hazard ratio [HR], 0.57; P = .004) and OS (HR, 0.62; P = .029). The median PFS was 10.6 months in the TKI alone group and 17.1 months in the TKI plus TRT group. The median OS was 26.2 months and 34.4 months in the TKI alone group and TKI plus TRT group, respectively. The TKI plus TRT group showed better local control but was associated with a higher incidence of severe TRAEs (11.9% v 5.1%). CONCLUSION: For patients with EGFR-mutated oligo-organ metastatic NSCLC treated with first-line EGFR-TKIs, concurrent TRT improves the PFS and OS, and TRAEs are acceptable and tolerable.