FOSL1 promotes proneural-to-mesenchymal transition of glioblastoma stem cells via UBC9/CYLD/NF-κB axis.

Proneural (PN) to mesenchymal (MES) transition (PMT) is a crucial phenotypic shift in glioblastoma stem cells (GSCs). However, the mechanisms driving this process remain poorly understood. Here, we report that Fos-like antigen 1 (FOSL1), a component of AP1 transcription factor complexes, is a key player in regulating PMT. FOSL1 is predominantly expressed in the MES subtype, but not PN subtype, of GSCs. Knocking down FOSL1 expression in MES GSCs leads to the loss of MES features and tumor-initiating ability, whereas ectopic expression of FOSL1 in PN GSCs is able to induce PMT and maintain MES features. Moreover, FOSL1 facilitates ionizing radiation (IR)-induced PMT and radioresistance of PN GSCs. Inhibition of FOSL1 enhances the anti-tumor effects of IR by preventing IR-induced PMT. Mechanistically, we find that FOSL1 promotes UBC9-dependent CYLD SUMOylation, thereby inducing K63-linked polyubiquitination of major nuclear factor κB (NF-κB) intermediaries and subsequent NF-κB activation, which results in PMT induction in GSCs. Our study underscores the importance of FOSL1 in the regulation of PMT and suggests that therapeutic targeting of FOSL1 holds promise to attenuate molecular subtype switching in patients with glioblastomas.

[Modern research progress in external application of traditional Chinese medicine to acupoints].

Traditional Chinese medicine(TCM) has a long history and abundant experience in external therapy, which marks human wisdom. In the early history of human, people found that fumigation, coating, and sticking of some tree branches and herb stems can help alleviate scabies and remove parasites in productive labor, which indicates the emergence of external therapy. Pathogen usually enters the body through the surface, so external therapy can be used to treat the disease. External therapy is among the major characteristic of surgery of TCM. As one of the external therapies in TCM, external application to acupoints smooths the zang-fu organs through meridians and collaterals, thereby harmonizing yin and yang. This therapy emerged in the early society, formed the Spring and Autumn Period and the Warring States Period, improved in the Song and Ming dynasties, and matured in the Qing dynasty. With the efforts of experts in history, it has had a mature theory. According to modern research, it can avoid the first-pass effect of liver and the gastrointestinal irritation and improve the bioavailability of Chinese medicine. Based on the effect of Chinese medicine and the theory of meridian and collateral, it can stimulate the acupoints, exert regulatory effect on acupoints, and give full play to the efficacy of TCM and the interaction of the two. Thereby, it can regulate qi and blood and balance yin and yang, thus being widely used in the treatment of diseases. In this paper, the use of external application to acupoints, the effect on skin immunity, the regulation of neuro-inflammatory mechanism, the relationship between acupoint application and human circulation network, and the development of its dosage form were summarized through literature review. On this basis, this study is expected to lay a foundation for further research.

[Intrinsic "self-consistent" phenomenon based on holistic view of traditional Chinese medicine].

The fundamental principle of traditional Chinese medicine(TCM) is holism, and it is crucial for TCM to address the key issue of the "holistic view" of Chinese herbal medicine. While the overall regulatory effects of Chinese herbal medicine have been widely recognized, the holistic internal logic of individual ingredients of Chinese herbal medicines require further clarification. In order to comprehensively understand the mechanism of action of Chinese herbal medicine, this paper combined the holistic view of Chinese herbal medicine with differentiation thinking to explore the intrinsic logical relationships within Chinese herbal medicine. Starting from the perspective of the coexistence of multiple components in Chinese herbal medicine, this paper systematically examined the "self-consistent" phenomenon within single Chinese herbal medicine. This phenomenon refers to the consistent or opposing actions of various components in terms of their physical and chemical properties, pharmacokinetic effects, biological effects, flavors and properties, and TCM efficacy. The paper summarized various logical relationships of syndrome differentiation exhibited by the same Chinese herbal medicine, analyzed the underlying reasons, and focused on analyzing external factors affecting the "self-consistent" phenomenon in the efficacy of Chinese herbal medicine, aiming to better elucidate the theoretical basis of the pharmacological effects of Chinese herbal medicine, further enrich the scientific connotation of the holistic view of Chinese herbal medicine, and provide theoretical guidance for the preparation process, compatibility patterns, and formulation design of Chinese herbal medicine.

[Pharmacokinetics, pharmacodynamics, and tissue distribution of oral co-loaded puerarin/daidzein mixed micelles in rats].

This study investigated the drug delivery performance of oral co-loaded puerarin(PUE) and daidzein(DAZ) mixed micelles(PUE/DAZ-FS/PMMs) from the perspectives of pharmacokinetics, pharmacodynamics, and tissue distribution. The changes in PUE plasma concentration in rats were evaluated based on PUE suspension, single drug-loaded micelles(PUE-FS/PMMs), and co-loaded micelles(PUE/DAZ-FS/PMMs). Spontaneously hypertensive rats(SHR) were used to monitor systolic blood pressure, diastolic blood pressure, and mean arterial pressure for 10 weeks after administration by tail volume manometry. The content of PUE in the heart, liver, spleen, lung, kidney, brain, and testes was determined using LC-MS/MS. The results showed that compared with PUE suspension and PUE-FS/PMMs, PUE/DAZ-FS/PMMs significantly increased C_(max) in rats(P<0.01) and had a relative bioavailability of 122%. The C_(max), AUC_(0-t), AUC_(0-∞), t_(1/2), and MRT of PUE/DAZ-FS/PMMs were 1.77, 1.22, 1.22, 1.17, and 1.13 times higher than those of PUE suspension, and 1.76, 1.16, 1.08, 0.84, and 0.78 times higher than those of PUE-FS/PMMs, respectively. Compared with the model control group, PUE/DAZ-FS/PMMs significantly reduced systolic blood pressure, diastolic blood pressure, and mean arterial pressure in SHR rats(P<0.05). The antihypertensive effect of PUE/DAZ-FS/PMMs was greater than that of PUE suspension, and even greater than that of PUE-FS/PMMs at high doses. Additionally, the distribution of PMMs in various tissues showed dose dependency. The distribution of PMMs in the kidney and liver, which are metabolically related tissues, was lower than that in the suspension group, while the distribution in the brain was higher than that in the conventional dose group. In conclusion, PUE/DAZ-FS/PMMs not only improved the bioavailability of PUE and synergistically enhanced its therapeutic effect but also prolonged the elimination of the drug to some extent. Furthermore, the micelles facilitated drug penetration through the blood-brain barrier. This study provides a foundation for the development of co-loaded mixed micelles containing homologous components.

Sulfone-Decorated Conjugated Organic Polymers Activate Oxygen for Photocatalytic Methane Conversion.

Oxidizing CH4 into liquid products with O2 under mild conditions still mainly relies on metal catalysis. We prepared a series of sulfone-modified conjugated organic polymers and found that the catalyst with proper SVI content (0.10) could drive O2 →H2 O2 →⋅OH to oxidize CH4 into CH3 OH and HCOOH directly and efficiently at room temperature under light irradiation. Experimental results showed that after 4 h reaction, decomposition rate and residual amounts of H2 O2 were 81.21 % and 4.83 mmol gcat -1 respectively, and CH4 conversion rate was 22.81 %. Mechanism studies revealed that illumination could induce the homolytic dissociation of S=O bonds on catalyst to produce oxygen and sulfur radicals, where the ⋅O could adsorb and activate CH4 , and the ⋅S could supply electrons for 1 O2 to generate H2 O2 and then for decomposing the H2 O2 into ⋅OH timely to oxidize CH4 . This research provided a novel organic catalysis approach for oxygen activation and utilization.

[Research advances in chemical constituents and pharmacological activities of Pueraria genus].

Kudzu plants in the subfamily sphenoideae of Leguminosae are commonly used herbs in China, Japan, Korea, India and Thailand, with a long history of medicinal use. They are recorded in Chinese Pharmacopoeia, Japanese Pharmacopeia, Korea Pharmacopeia, Ayurveda Pharmacopoeia of India and Flora of Thailand. There are 15-20 species of Pueraria in the world, including 7 species and 2 varieties in China. At present, there are 6 species with medicinal value, such as Pueraria lobata and P. thomsonii. The main chemical components of the genus are isoflavones, flavonoids, terpenes, steroids, coumarins, puerarin glycosides and benzopyrans. A total of 240 compounds have been isolated and identified from this genus, and their pharmacological effects mainly include improvement of the cardiovascular system, antioxidant, hypoglycemic, antipyretic, anti-inflammatory, anti-alcoholic and estrogen-like effects. In this study, chemical constituents and pharmacological activities of Pueraria at home and abroad were systematically summarized, in order to provide references for the material basis, quality control and further development of Pueraria genus.

[Pharmaceutics research advances in oral administration of puerarin].

Puerarin is a naturally occurring isoflavone C-glycoside,isolated from the root of Pueraria lobata,which has attracted extensive attention in the medical circles because of its various pharmacological effects,such as vasodilation,cardioprotection,neuroprotection,antioxidant,anticancer,anti-inflammation,alleviating pain,promoting bone formation,inhibiting alcohol intake,and attenuating insulin resistance. However,its low oral bioavailability has limited its clinical application. This review gives a comprehensive summary of the researches on physicochemical properties,pharmacokinetics( absorption,distribution,metabolism and excretion,pharmacokinetic parameters) in oral administration,and pharmaceutics research strategies of puerarin in recent years,and the in vivo behavior difference between multicomponent and single component environment was also summarized. The reasons( low water solubility,poor membrane permeability,short half-life,inhibition of P-gp efflux and first-pass metabolic effects of intestinal enzymes,etc.) for low bioavailability were concluded and the idea that multicomponent enviroment would affect the bioavailability was clarified. The aim of this review is to provide literature basis for the development of new dosage forms and new technologies for multivariate compound drug delivery system to improve the bioavailability of oral puerarin,and to propose ways to improve the bioavailability of BCS Ⅳ drugs derived from traditional Chinese medicine by fully enlarging the synergistic effect of multi-components or reasonably using the inhibitory effect between components.

Catalytic asymmetric dearomatization (CADA) reactions of phenol and aniline derivatives.

Phenols are widely used as starting materials in both industrial and academic society. Dearomatization reactions of phenols provide an efficient way to construct highly functionalized cyclohexadienones. The main challenge to make them asymmetric by catalytic methods is to control the selectivity while overcoming the loss of aromaticity. In this tutorial review, an up to date summary of recent progress in CADA reactions of phenol and aniline derivatives is presented.

Platinum-Catalyzed Allylation of 2,3-Disubstituted Indoles with Allylic Acetates.

Given the importance of heterocycle indole derivatives, much effort has been directed toward the development of methods for functionalization of the indole nucleus at N1 and C3 sites. Moreover, the platinum-catalyzed allyation of nucleophiles was an established and efficient way, which has been applied to medicinal and organic chemistry. In our research, the platinum-catalyzed 2,3-disubstitued indoles with allylic acetates was investigated under different conditions. Herein, we established a simple, convenient, and efficient method, which afforded high yield of allylated indoles.

Construction of erythrinane skeleton via Pd(0)-catalyzed intramolecular dearomatization of para-aminophenols.

A novel Pd(0)-catalyzed intramolecular arylative dearomatization of para-aminophenol derivatives is described. In the presence of 1.25 mol % [Pd(C3H5)Cl]2 and 3.75 mol % RuPhos, the arylative dearomatization reaction proceeds smoothly for a broad range of substrates, offering an efficient synthetic route to erythrinane derivatives in excellent yields.

Autoimmune encephalitis following treatment with durvalumab for small-cell lung cancer.

The traditional treatment for small-cell lung cancer (SCLC) has been traditional systemic platinum-containing chemotherapy because the response rate is 50-90%. Durvalumab is an immune checkpoint inhibitor that blocks the binding of programmed cell death protein 1 and programmed cell death 1 ligand 1. Durvalumab combined with traditional chemotherapy agents has been recommended as the first-line treatment for extensive-stage SCLC, but its use may cause immune-related adverse events. Autoimmune encephalitis is a rare and potentially fatal neurological adverse event. This current case report describes a male patient in his late 50s with ES-SCLC who developed autoimmune encephalitis associated with durvalumab treatment after three cycles of combination chemotherapy. This current case furthers the understanding of autoimmune encephalitis caused by durvalumab treatment.

Augmented fluoroscopy-guided dye localization for small pulmonary nodules in hybrid operating room: intrathoracic stamping versus transbronchial marking.

PURPOSE: We developed a novel augmented fluoroscopy-guided intrathoracic stamping technique for localizing small pulmonary nodules in the hybrid operating room. We conducted an observational study to investigate the feasibility of this technique and retrospectively compared two augmented fluoroscopy-guided approaches: intrathoracic and transbronchial. METHODS: From August 2020 to March 2023, consecutive patients underwent single-stage augmented fluoroscopy-guided localization under general anaesthesia. This included intrathoracic stamping and bronchoscopic lung marking, followed by thoracoscopic resection in a hybrid operating room. Comparative analyses were performed between the two groups. RESULTS: The data of 50 patients in the intrathoracic stamping and 67 patients in the bronchoscopic lung marking groups were analysed. No significant difference was noted in demographic data between the groups, except a larger lesion depth in the bronchoscopic lung marking group (14.7 ± 11.7 vs 11.0 ± 5.8 mm, p = 0.029). Dye localization was successfully performed in 49 intrathoracic stamping group patients (98.0%) and 67 bronchoscopic lung marking group patients (100%). No major procedure-related complications occurred in either group; however, the time flow (total anaesthesia time/global operating room time) was longer, and the radiation exposure (fluoroscopy duration/total dose area product) was larger in the bronchoscopic lung marking group. CONCLUSIONS: Augmented fluoroscopic stamping localization under intubated general anaesthesia is feasible and safe, providing an alternative with less global operating room time and lower radiation exposure for image-guided thoracoscopic surgery in the hybrid operating room.

Rhizoma Atractylodis Macrocephalae-Assessing the influence of herbal processing methods and improved effects on functional dyspepsia.

Background: The unique pharmaceutical methods for the processing of botanical drugs according to the theory of traditional Chinese medicine (TCM) affect clinical syndrome differentiation and treatment. The objective of this study was to comprehensively elucidate the principles and mechanisms of an herbal processing method by investigating the alterations in the metabolites of Rhizoma Atractylodis Macrocephalae (AMR) processed by Aurantii Fructus Immaturus (AFI) decoction and to determine how these changes enhance the efficacy of aqueous extracts in treating functional dyspepsia (FD). Methods: A qualitative analysis of AMR before and after processing was conducted using UPLC-Q-TOF-MS/MS, and HPLC was employed for quantitative analysis. A predictive analysis was then conducted using a network analysis strategy to establish a botanical drug-metabolite-target-disease (BMTD) network and a protein-protein interaction (PPI) network, and the predictions were validated using an FD rat model. Results: A total of 127 metabolites were identified in the processed AMR (PAMR), and substantial changes were observed in 8 metabolites of PAMR after processing, as revealed by the quantitative analysis. The enhanced aqueous extracts of processed AMR (PAMR) demonstrate improved efficacy in treating FD, which indicates that this processing method enhances the anti-inflammatory properties and promotes gastric motility by modulating DRD2, SCF, and c-kit. However, this enhancement comes at the cost of attenuating the regulation of motilin (MTL), gastrin (GAS), acetylcholine (Ach), and acetylcholinesterase (AchE). Conclusion: Through this series of investigations, we aimed to unravel the factors influencing the efficacy of this herbal formulation in improving FD in clinical settings.

Novel Inflammasome-Based Risk Score for Predicting Survival and Efficacy to Immunotherapy in Early-Stage Non-Small Cell Lung Cancer.

Immune checkpoint inhibitors (ICI) for early-stage non-small cell lung cancer (NSCLC) have been approved to improve outcomes and reduce recurrence. Biomarkers for patient selection are needed. In this paper, we proposed an inflammasome-based risk score (IRS) system for prognosis and prediction of ICI response for early-stage NSCLC. Cox regression analysis was used to identify significant genes (from 141 core inflammasome genes) for overall survival (OS) in a microarray discovery cohort (n = 467). IRS was established and independently validated by other datasets (n = 1320). We evaluated the inflammasome signaling steps based on five gene sets, which were IL1B-, CASP-1-, IL18-, GSDMD-, and inflammasome-regulated genes. Gene set enrichment analysis, the Kaplan-Meier curve, receiver operator characteristic with area under curve (AUC) analysis, and advanced bioinformatic tools were used to confirm the ability of IRS in prognosis and classification of patients into ICI responders and non-responders. A 30-gene IRS was developed, and it indicated good risk stratification at 10-year OS (AUC = 0.726). Patients were stratified into high- and low-risk groups based on optimal cutoff points, and high-risk IRS had significantly poorer OS and relapse-free survival. In addition, the high-risk group was characterized by an inflamed immunophenotype and higher proportion of ICI responders. Furthermore, expression of SLAMF8 was the key gene in IRS and indicated good correlation with biomarkers associated with immunotherapy. It could serve as a therapeutic target in the clinical setting of immunotherapy.

The Novel Use of PVP K30 as Templating Agent in Production of Porous Lactose.

It is necessary to prepare porous lactose in order to improve the dissolution behavior of insoluble active ingredient. In this study, polyvinylpyrrolidone K30 (PVP K30) was firstly utilized as a templating agent with different use levels in preparing porous lactose. Then, the physical properties were profoundly characterized. Finally, the porous lactose was also employed as a health functional food/drug carrier to explore the effect on the dissolution behavior of curcumin. The results confirmed that (i) porous lactose was successfully prepared using PVP K30 as templating agent; (ii) PVP K30 significantly improved the yield of lactose in the spray drying; (iii) the improved powder properties of porous lactose were more conducive to the downstream operating process for the preparation of health functional food or drug; and (iv) the porous lactose significantly improved the dissolution behavior of curcumin. Therefore, the results obtained are beneficial to boosting the development of porous materials.

Noise suppressions in synchronized chaos lidars.

The noise suppressions in the chaos lidar (CLIDAR) and the synchronized chaos lidar (S-CLIDAR) systems with the optoelectronic feedback (OEF) and optical feedback (OF) schemes are studied numerically. Compared with the CLIDAR system, the S-CLIDAR system with the OEF scheme has better correlation coefficients in the large noise regime for SNR < 15 dB. For the S-CLIDAR system with the OF scheme, better detections are also achieved in wide ranges depending on the levels of the phase noise presented in the channel. To have the best synchronization and detection quality, the optimized conditions for the coupling and feedback strengths in the S-CLIDAR system are also discussed.

Analysis of genome expression in the response of Oryza granulata to Xanthomonas oryzae pv oryzae.

In order to understand the mechanism of the strong resistance of Oryza granulata to Xanthomonas oryzae pv oryzae (Xoo), cDNA microarrays containing 2,436 cDNA clones of Oryza granulata derived from Suppression subtractive library and cDNA library were constructed and genome expression patterns after inoculating Xoo were investigated. Three hundred and 83 clones were up-regulated, 836 clones were down-regulated after pathogen infection. Approximately 800 clones were sequenced and BLAST search were carried out. There are no homologous sequences for 35 clones of them. The functions of the homologous sequences for most clones are unknown. The known functions of the homologous sequences involved in photosynthesis, respiration, material transport, signal transduction, pathogenesis-related proteins, transcription factors, the active oxygen scavenging system and so on. The putative functions of them in responding to Xoo were discussed.

Protective Effect of Statins on Pulmonary Hypertension in Chronic Obstructive Pulmonary Disease Patients: A Nationwide Retrospective, Matched Cohort Study.

In Taiwan, patients with pulmonary hypertension (PH) related to chronic obstructive pulmonary disease (COPD) are most common PH population (group 3). However, efficacy of medical treatments and optimal prevention methods in this group remain uncertain. Statins such as indirect RhoA/Rho-kinase inhibitors influence one of key signalling pathways that promote PH onset. In this study, we explored protective effects of statins against PH in COPD patients using database from Taiwan National Health Insurance programme from 2002 to 2017. The main outcome was the risk of PH. The Cox proportional-hazards model and the Fine and Gray model were used to adjust covariate and competing risks to estimate the subdistribution hazard ratios (sHRs). 553,617 newly diagnosed COPD patients were stratified by statin users (n = 41,168) and statin nonusers (n = 512,449). After 1:1 propensity score matching of statin users (n = 41,163), and 41,163 statin nonusers were included for outcome analysis. Statin users had a 22% lower risk of PH than nonusers (sHR: 0.78, 95% confidence interval: 0.65-0.94). During subgroup analysis, taking higher daily doses and for a longer duration displayed a more significantly reduced risk of PH (both P for trend <0.001). Statins may have a protective effect against PH that is dose- and time-dependent.

Gold-Catalyzed Intramolecular Dearomatization Reactions of Indoles for the Synthesis of Spiroindolenines and Spiroindolines.

A gold-catalyzed dearomatization reaction of indole derivatives was realized in the presence of JohnPhosAuCl/AgOMs to afford a series of spiroindolenines in excellent yields (≤99%). In addition, when the Hantzsch ester was used as the hydrogen transfer reagent, various spiroindolines were obtained in a cascade fashion starting from readily available indole derivatives in modest to good yields (≤79%). Both reactions feature readily available substrates, mild conditions, and good functional group tolerance.

Construction of Spironaphthalenones via Gold-Catalyzed Intramolecular Dearomatization Reaction of ß-Naphthol Derivatives.

A gold-catalyzed dearomatization reaction of ß-naphthol derivatives via intramolecular hydroalkylation of alkynes is described. In the presence of 5 mol % Au complex, various spironaphthalenones were obtained from α-tethered alkyne ß-naphthols in good to excellent yields (76-99%) under open-flask conditions.