Investigating the relationship between postoperative radiotherapy and intestinal flora in rectal cancer patients: a study on efficacy and radiation enteritis.

Objective: This study aimed to investigate the impact of radiation therapy and radiation enteritis on intestinal flora, providing insights for treatment and prevention. Methods: Fecal samples were collected from 16 patients undergoing pelvic radiotherapy at Qingdao Hiser Hospital Affiliated of Qingdao University (Qingdao Traditional Chinese Medicine Hospital). Samples were collected before and after radiotherapy (27-30Gy), and analyzed using DNA sequencing and biostatistical methods. Results: Patients with radiation enteritis showed increased α-diversity and ß-diversity of intestinal flora compared to those without radiation enteritis. Differences in flora composition were observed, with higher abundance of secondary pathways such as amino acid metabolism, carbohydrate metabolism, cofactors and vitamins metabolism, and lipid metabolism. Conclusion: The study revealed that patients developing radiation enteritis during pelvic radiation therapy had increased diversity and abundance of intestinal flora compared to those who did not develop radiation enteritis. Additionally, patients without radiation enteritis showed significantly higher diversity and abundance of intestinal flora post-radiation compared to pre-radiation.

The Difference between Plasmon Excitations in Chemically Heterogeneous Gold and Silver Atomic Clusters.

Weak doping can broaden, shift, and quench plasmon peaks in nanoparticles, but the mechanistic intricacies of the diverse responses to doping remain unclear. In this study, we used the time-dependent density functional theory (TD-DFT) to compute the excitation properties of transition-metal Pd- or Pt-doped gold and silver atomic arrays and investigate the evolution characteristics and response mechanisms of their plasmon peaks. The results demonstrated that the Pd or Pt doping of the off-centered 10 × 2 atomic arrays broadened or shifted the plasmon peaks to varying degrees. In particular, for Pd-doped 10 × 2 Au atomic arrays, the broadened plasmon peak significantly blueshifted, whereas a slight red shift was observed for Pt-doped arrays. For the 10 × 2 Ag atomic arrays, Pd doping caused almost no shift in the plasmon peak, whereas Pt doping caused a substantial red shift in the broadened plasmon peak. The analysis revealed that the diversity in these doping responses was related to the energy positions of the d electrons in the gold and silver atomic clusters and the positions of the doping atomic orbitals in the energy bands. The introduction of doping atoms altered the symmetry and gap size of the occupied and unoccupied orbitals, so multiple modes of single-particle transitions were involved in the excitation. An electron transfer analysis indicated a close correlation between excitation energy and the electron transfer of doping atoms. Finally, the differences in the symmetrically centered 11 × 2 doped atomic array were discussed using electron transfer analysis to validate the reliability of this analytical method. These findings elucidate the microscopic mechanisms of the evolution of plasmon peaks in doped atomic clusters and provide new insights into the rational control and application of plasmons in low-dimensional nanostructures.

Quercetin protects against hypertensive renal injury by attenuating apoptosis: an integrated approach using network pharmacology and RNA-Seq.

Quercetin is kown for its antihypertensive effects. However, its role on hypertensive renal injury has not been fully eucidated. In this study, hematoxylin and eosin staining, terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL) staining, and Annexin V staining were used to assess the pathological changes and cells apoptosis in the renal tissues of Ang II-infused mice and Ang II- stimulated renal tubular epithelial cell line (NRK-52E). A variety of technologies, including network pharmacology, RNA-sequencing, immunohistochemistry, and Western blotting were performed to investigate its underlying mechanisms. Network pharmacology analysis identified multiple potential candidate targets (including TP53, Bcl-2 and Bax) and enriched signaling pathways (including apoptosis and p53 signaling pathway). Quercetin treatment significantly alleviated the pathological changes in renal tissues of Ang II-infused mice and reversed 464 differentially expressed transcripts (DETs), as well as enriched several signaling pathways, including those related apoptosis and p53 pathway. Furthermore, quercetin treatment significantly inhibited the cell apoptosis in renal tissues of Ang II-infused mice and Ang II-stimulated NRK-52E cells. Additionally, quercetin treatment inhibited the upregulation of p53, Bax, cleaved-caspase-9, and cleaved-caspase-3 protein expression and the downregulation of Bcl-2 protein expression in both renal tissue of Ang II-infused mice and Ang II-stimulated NRK-52E cells. Moreover, the molecular docking results indicated a potential binding interaction between quercetin and TP53. Quercetin treatment significantly attenuated hypertensive renal injury and cell apoptosis in renal tissues of Ang II-infused mice and Ang II-stimulated NRK-52E cells, and by targeting p53 may be one of the potential underlying mechanisms.

Correlation analysis of secondary metabolites and disease resistance activity of different varieties of Congou black tea based on LC-MS/MS and TCMSP.

To investigate the correlation between the difference of secondary metabolites and the disease-resistance activity of different varieties of Congou black tea. Among a total of 657 secondary metabolites identified, 183 metabolites had anti-disease activity, 113 were key active ingredients in traditional Chinese medicine (TCM), 73.22% had multiple anti-disease activities, and all were mainly flavonoids and phenolic acids. The main enriched metabolic pathways were phenylpropanoid biosynthesis, biosynthesis of secondary metabolites, flavonoid biosynthesis, and metabolic pathways. Flavonoid and phenolic acid secondary metabolites were more correlated with anti-disease activity and key active TCM ingredients. Conclusion: The types of JGY and Q601 Congou black tea of the relative contents show large differences in secondary metabolites. Flavonoid and phenolic acid secondary metabolites were identified as the primary factors contributing to the variation in secondary metabolites among different varieties of Congou black tea. These compounds also exhibited a stronger correlation with disease resistance activity.

N-Salicyloyl Tryptamine Derivatives as Potent Neuroinflammation Inhibitors by Constraining Microglia Activation via a STAT3 Pathway.

Neuroinflammation is an important factor that exacerbates neuronal death and abnormal synaptic function in neurodegenerative diseases (NDDs). Due to the complex pathogenesis and the presence of blood-brain barrier (BBB), no effective clinical drugs are currently available. Previous results showed that N-salicyloyl tryptamine derivatives had the potential to constrain the neuroinflammatory process. In this study, 30 new N-salicyloyl tryptamine derivatives were designed and synthesized to investigate a structure-activity relationship (SAR) for the indole ring of tryptamine in order to enhance their antineuroinflammatory effects. Among them, both in vitro and in vivo compound 18 exerted the best antineuroinflammatory effects by suppressing the activation of microglia, which is the culprit of neuroinflammation. The underlying mechanism of its antineuroinflammatory effect may be related to the inhibition of transcription, expression and phosphorylation of signal transducer and activator of transcription 3 (STAT3) that subsequently regulated downstream cyclooxygenase-2 (COX-2) expression and activity. With its excellent BBB permeability and pharmacokinetic properties, compound 18 exhibited significant neuroprotective effects in the hippocampal region of lipopolysaccharides (LPS)-induced mice than former N-salicyloyl tryptamine derivative L7. In conclusion, compound 18 has provided a new approach for the development of highly effective antineuroinflammatory therapeutic drugs targeting microglia activation.

Potential therapeutic targets of the JAK2/STAT3 signaling pathway in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) poses a significant clinical challenge due to its propensity for metastasis and poor prognosis. TNBC evades the body's immune system recognition and attack through various mechanisms, including the Janus Kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway. This pathway, characterized by heightened activity in numerous solid tumors, exhibits pronounced activation in specific TNBC subtypes. Consequently, targeting the JAK2/STAT3 signaling pathway emerges as a promising and precise therapeutic strategy for TNBC. The signal transduction cascade of the JAK2/STAT3 pathway predominantly involves receptor tyrosine kinases, the tyrosine kinase JAK2, and the transcription factor STAT3. Ongoing preclinical studies and clinical research are actively investigating this pathway as a potential therapeutic target for TNBC treatment. This article comprehensively reviews preclinical and clinical investigations into TNBC treatment by targeting the JAK2/STAT3 signaling pathway using small molecule compounds. The review explores the role of the JAK2/STAT3 pathway in TNBC therapeutics, evaluating the benefits and limitations of active inhibitors and proteolysis-targeting chimeras in TNBC treatment. The aim is to facilitate the development of novel small-molecule compounds that target TNBC effectively. Ultimately, this work seeks to contribute to enhancing therapeutic efficacy for patients with TNBC.

Discovery of novel small molecules targeting the USP21/JAK2/STAT3 axis for the treatment of triple-negative breast cancer.

The deficiency in available targeted agents and frequency of chemoresistance are primary challenges in clinical management of triple-negative breast cancer (TNBC). The aberrant expression of USP21 and JAK2 represents a characterized mechanism of TNBC progression and resistance to paclitaxel (PTX). Despite its clear that high expression of USP21-mediated de-ubiquitination leads to increased levels of JAK2 protein, we lack regulator molecules to dissect the mechanisms that the interaction between USP21 and JAK2 contributes to the phenotype and resistance of TNBC. Here, we report a USP21/JAK2/STAT3 axis-targeting regulator 13c featuring a N-anthraniloyl tryptamine scaffold that showed excellent anti-TNBC potency and promising safety profile. Importantly, the therapeutic potential of using 13c in combination with PTX in PTX-resistant TNBC was demonstrated. This study showcases N-anthraniloyl tryptamine derivatives as a novel anti-TNBC chemotype with a pharmacological mode of action targeting the USP21/JAK2/STAT3 axis and provides a potential therapeutic target for the treatment of TNBC.

Splicing factor hnRNPA1 regulates alternative splicing of LOXL2 to enhance the production of LOXL2Δ13.

Lysyl oxidase-like 2 (LOXL2) is a member of the lysyl oxidase family and has the ability to catalyze the cross-linking of extracellular matrix collagen and elastin. High expression of LOXL2 is related to tumor cell proliferation, invasion, and metastasis. LOXL2 contains 14 exons. Previous studies have found that LOXL2 has abnormal alternative splicing and exon skipping in a variety of tissues and cells, resulting in a new alternatively spliced isoform denoted LOXL2Δ13. LOXL2Δ13 lacks LOXL2WT exon 13, but its encoded protein has greater ability to induce tumor cell proliferation, invasion, and metastasis. However, the molecular events that produce LOXL2Δ13 are still unclear. In this study, we found that overexpression of the splicing factor hnRNPA1 in cells can regulate the alternative splicing of LOXL2 and increase the expression of LOXL2Δ13. The exonic splicing silencer exists at the 3' splice site and 5' splice site of LOXL2 exon 13. HnRNPA1 can bind to the exonic splicing silencer and inhibit the inclusion of exon 13. The RRM domain of hnRNPA1 and phosphorylation of hnRNPA1 at S91 and S95 are important for the regulation of LOXL2 alternative splicing. These results show that hnRNPA1 is a splicing factor that enhances the production of LOXL2Δ13.

Implications of intestinal microecology and immune function alterations for immunotherapy outcomes in advanced unresectable lung adenocarcinoma.

OBJECTIVE: This investigation aims to explore alterations in intestinal microecology and immune function among patients with advanced, unresectable lung adenocarcinoma undergoing different outcomes from immunotherapy. METHODS: A cohort of 30 patients diagnosed with advanced unresectable lung adenocarcinoma received sintilimab immunotherapy as a monotherapy. Post four treatment cycles, efficacy was assessed, leading to the segregation of patients into two distinct cohorts: those responsive to treatment and those nonresponsive. Analysis involved observing variations in the abundance, distribution, and composition of fecal intestinal microorganisms pretreatment and posttreatment via 16S rRNA gene sequencing. RESULTS: In this study involving 30 advanced lung adenocarcinoma patients, significant observations were made regarding the impact of immunotherapy on immune function and the gut microbiome composition. Patients were divided into treatment and control groups, revealing that immunotherapy led to a significant increase in CD4+ T cells and a decrease in CD8+ T cells among the treatment-responsive individuals, indicating an enhanced immune response. Furthermore, an in-depth analysis of the gut microbiome showed an increase in diversity and abundance of beneficial bacteria such as Faecalibacterium and Subdoligranulum in the treatment group. These findings highlight the dual effect of immunotherapy on modulating immune function and altering gut microbiome diversity, suggesting its potential therapeutic benefits in improving the health status of patients with advanced lung adenocarcinoma. CONCLUSION: The structuring of gut flora plays a pivotal role in augmenting the efficacy of anti-tumor immunotherapy, underscoring the interplay between intestinal microecology and immune response in cancer treatment outcomes.

Inhibitory effect of benzocaine from Schisandra chinensis on Alternaria alternata.

The clinical effects of Schisandra chinensis against human disease are well-documented; however, studies on its application in controlling plant pathogens are limited. Here, we investigated its inhibitory effect on the growth of Alternaria alternata, a fungus which causes significant post-harvest losses on apples, known as black spot disease. S. chinensis fruit extract exhibited strong inhibitory effects on the growth of A. alternata with an EC50 of 1882.00 mg/L. There were 157 compounds identified in the extract by high performance liquid chromatography-mass spectrometry, where benzocaine constituted 14.19% of the extract. Antifungal experiments showed that the inhibitory activity of benzocaine on A. alternata was 43.77-fold higher than the crude extract. The application of benzocaine before and after A. alternata inoculation on apples prevented the pathogen infection and led to mycelial distortion according to scanning electron microscopy. Transcriptome analysis revealed that there were 4226 genes differentially expressed between treated and untreated A. alternata-infected apples with benzocaine. Metabolomics analysis led to the identification of 155 metabolites. Correlation analysis between the transcriptome and metabolome revealed that benzocaine may inhibit A. alternata growth via the beta-alanine metabolic pathway. Overall, S. chinensis extract and benzocaine are environmentally friendly plant-based fungicides with potential to control A. alternata.

Antibody-Protein-Aptamer Electrochemical Biosensor based on Highly Efficient Proximity-Induced DNA Hybridization on Tetrahedral DNA Nanostructure for Sensitive Detection of Insulin-like Growth Factor-1.

Herein, an antibody-protein-aptamer electrochemical biosensor was designed by highly efficient proximity-induced DNA hybridization on a tetrahedral DNA nanostructure (TDN) for ultrasensitive detection of human insulin-like growth factor-1 (IGF-1). Impressively, the IGF-1 antibody immobilized on the top vertex of the TDN could effectively capture the target protein with less steric effect, and the ferrocene-labeled signal probe (SP) bound on the bottom vertex of the TDN was close to the electrode surface for generating a strong initial signal. In the presence of target protein IGF-1 and an aptamer strand, an antibody-protein-aptamer sandwich could be formed on the top vertex of TDN, which would trigger proximity-induced DNA hybridization to release the SP on the bottom vertex of TDN; therefore, the signal response would decrease dramatically, enhancing the sensitivity of the biosensor. As a result, the linear range of the proposed biosensor for target IGF-1 was 1 fM to 1 nM with the limit of detection down to 0.47 fM, which was much lower than that of the traditional TDN designs on electrochemical biosensors. Surprisingly, the use of this approach offered an innovative approach for the sensitive detection of biomarkers and illness diagnosis.

Analysis of the chain-mediated effects of nurses' sense of professional gain and sense of professional mission between psychological resilience and work engagement in 10 general hospitals in Sichuan province.

Objective: To explore the chain-mediated role of sense of career benefit and sense of career mission in the mechanism of psychological flexibility's effect on nurses' work engagement. Methods: Adopting the convenience sampling method, 1032 nurses in 10 general hospitals in Sichuan Province were surveyed by questionnaires using the General Information Questionnaire, Sense of Occupational Benefit Scale, Sense of Occupational Mission Scale, Psychological Flexibility Scale, and work engagement Scale in August-October 2022, and the model of the chained-mediated effect was constructed and validated. Results: The total psychological resilience score of nurses in 10 general hospitals in Sichuan Province was (91.29 ± 17.38), the total score of sense of occupational benefit was (137.85 ± 21.02), the total score of sense of occupational mission was (40.27 ± 7.37), and the total score of work engagement was (34.99 ± 9.80). The total score of nurses' work engagement was positively correlated with the total scores of psychological elasticity, sense of professional benefit, and sense of professional mission (all P < 0.05). The direct effect of psychological elasticity on nurses' work engagement was significant, with an effect value of 0.321; the chain mediation effects of occupational benefit and occupational mission as separate mediators and the chain mediation effects of the two were 0.039, 0.032, and 0.062, respectively. Conclusion: Nurses' work engagement in 10 general hospitals in Sichuan province is at a medium level, and occupational benefit and occupational mission play a significant role in the mechanism of the psychological elasticity's effects on nurses' work commitment, and the chain mediation effect of occupational mission in the mechanism of psychological elasticity is established. The chain mediation effect in the mechanism was established. Managers should pay attention to nurses with low psychological elasticity, improve their sense of occupational benefit, and enhance their sense of occupational mission in order to further promote the enhancement of work engagement.

T2WI-based MRI radiomics for the prediction of preoperative extranodal extension and prognosis in resectable rectal cancer.

OBJECTIVE: To investigate whether T2-weighted imaging (T2WI)-based intratumoral and peritumoral radiomics can predict extranodal extension (ENE) and prognosis in patients with resectable rectal cancer. METHODS: One hundred sixty-seven patients with resectable rectal cancer including T3T4N + cases were prospectively included. Radiomics features were extracted from intratumoral, peritumoral 3 mm, and peritumoral-mesorectal fat on T2WI images. Least absolute shrinkage and selection operator regression were used for feature selection. A radiomics signature score (Radscore) was built with logistic regression analysis. The area under the receiver operating characteristic curve (AUC) was used to evaluate the performance of each Radscore. A clinical-radiomics nomogram was constructed by the most predictive radiomics signature and clinical risk factors. A prognostic model was constructed by Cox regression analysis to identify 3-year recurrence-free survival (RFS). RESULTS: Age, cT stage, and lymph node-irregular border and/or adjacent fat invasion were identified as independent clinical risk factors to construct a clinical model. The nomogram incorporating intratumoral and peritumoral 3 mm Radscore and independent clinical risk factors achieved a better AUC than the clinical model in the training (0.799 vs. 0.736) and validation cohorts (0.723 vs. 0.667). Nomogram-based ENE (hazard ratio [HR] = 2.625, 95% CI = 1.233-5.586, p = 0.012) and extramural vascular invasion (EMVI) (HR = 2.523, 95% CI = 1.247-5.106, p = 0.010) were independent risk factors for predicting 3-year RFS. The prognostic model constructed by these two indicators showed good performance for predicting 3-year RFS in the training (AUC = 0.761) and validation cohorts (AUC = 0.710). CONCLUSION: The nomogram incorporating intratumoral and peritumoral 3 mm Radscore and clinical risk factors could predict preoperative ENE. Combining nomogram-based ENE and MRI-reported EMVI may be useful in predicting 3-year RFS. CRITICAL RELEVANCE STATEMENT: A clinical-radiomics nomogram could help preoperative predict ENE, and a prognostic model constructed by the nomogram-based ENE and MRI-reported EMVI could predict 3-year RFS in patients with resectable rectal cancer. KEY POINTS: • Intratumoral and peritumoral 3 mm Radscore showed the most capability for predicting ENE. • Clinical-radiomics nomogram achieved the best predictive performance for predicting ENE. • Combining clinical-radiomics based-ENE and EMVI showed good performance for 3-year RFS.

Efficacy and safety of Qingda granule versus valsartan capsule in Chinese grade 1 hypertensive patients with low-moderate risk: A randomized, double-blind, double dummy, non-inferiority, multi-center trial.

BACKGROUND: The efficacy and safety of Qingda granule (QDG) in managing blood pressure (BP) among grade 1 hypertensive patients with low-moderate risk remain uncertain. METHODS: In the randomized, double-blind, double dummy, non-inferiority and multicenter trial, 552 patients with grade 1 hypertension at low-moderate risk were assigned at a ratio of 1:1 to receive either QDG or valsartan for 4 weeks, followed up by a subsequent 4 weeks. RESULTS: Post-treatment, clinic systolic/diastolic BPs (SBP/DBP) were reduced by a mean change of 9.18/4.04 mm Hg in the QDG group and 9.85/5.05 mm Hg in the valsartan group (SBP P = 0.47, DBP P = 0.16). Similarly, 24-hour, daytime and nighttime BPs were proportional in both groups (P > 0.05) after 4 weeks treatment. After discontinuing medications for 4 weeks, the mean reduction of clinic SBP/DBP were 0.29/0.57 mm Hg in the QDG group compared to -1.59/-0.48 mm Hg in the valsartan group (SBP P = 0.04, DBP P = 0.04). Simultaneously, the 24-hour SBP/DBP were reduced by 0.9/0.31 mm Hg in the QDG group and -1.66/-1.08 mm Hg in the valsartan group (SBP P = 0.006, DBP P = 0.02). And similar results were observed regarding the outcomes of daytime and nighttime BPs. There was no difference in occurrence of adverse events between two groups (P > 0.05). CONCLUSION: QDG proves to be efficacious for grade 1 hypertension at a low-to-medium risk, even after discontinuation of the medication for 4 weeks. These findings provide a promising option for managing grade 1 hypertension and suggest the potential for maintaining stable BP through intermittent administration of QDG. TRIAL REGISTRATION: ChiCTR2000033890.

Prediction of the SF-6D utility score from Lung cancer FACT-L: a mapping study in China.

OBJECTIVE: To develop a mapping algorithm for generating the Short Form Six-Dimension (SF-6D) utility score based on the Functional Assessment of Cancer Therapy-Lung (FACT-L) of lung cancer patients. METHODS: Data were collected from 625 lung cancer patients in mainland China. The Spearman rank correlation coefficient and principal component analysis were used to evaluate the conceptual overlap between the FACT-L and SF-6D. Five model specifications and four statistical techniques were used to derive mapping algorithms, including ordinary least squares (OLS), Tobit and beta-mixture regression models, which were used to directly estimate health utility, and ordered probit regression was used to predict the response level. The prediction performance was evaluated using the correlations between the root mean square error (RMSE), mean absolute error (MAE), concordance correlation coefficient (CCC), Akaike information criterion (AIC) and Bayesian information criterion (BIC) and the observed and predicted SF-6D scores. A five-fold cross-validation method was used to test the universality of each model and select the best model. RESULTS: The average FACT-L score was 103.024. The average SF-6D score was 0.774. A strong correlation was found between FACT-L and SF-6D scores (ρ = 0.797). The ordered probit regression model with the total score of each dimension and its square term, as well as age and sex as covariates, was most suitable for mapping FACT-L to SF-6D scores (5-fold cross-validation: RMSE = 0.0854; MAE = 0.0655; CCC = 0.8197; AEs > 0.1 (%) = 53.44; AEs > 0.05 (%) = 21.76), followed by beta-mixture regression for direct mapping. The Bland‒Altman plots showed that the ordered probit regression M5 had the lowest proportion of prediction scores outside the 95% agreement limit (-0.166, 0.163) at 4.96%. CONCLUSIONS: The algorithm reported in this paper enables lung cancer data from the FACT-L to be mapped to the utility of the SF-6D. The algorithm allows the calculation of quality-adjusted life years for cost-utility analyses of lung cancer.

Effect of hyperthermia on intestinal microecology, immune function, and progression-free survival in patients with advanced unresectable lung adenocarcinoma.

This study aims to investigate the effects of hyperthermia on intestinal microecology, immune function, and progression-free survival of patients with advanced unresectable lung adenocarcinoma. A total of twenty patients with lung adenocarcinoma in the study group received the advanced standard first-line treatment protocol, which included pemetrexed + cisplatin combined with sintilimab immunotherapy and hyperthermia. Additionally, twenty patients with lung adenocarcinoma in the control group received the advanced standard first-line treatment protocol, which included pemetrexed + cisplatin combined with sintilimab immunotherapy. The T-lymphocyte subpopulation and CD4/CD8 cell ratio of each sample were detected using flow cytometry. The intestinal flora was evaluated using 16S rRNA gene sequencing. The study observed the changes in the abundance, distribution, composition, and structure of fecal gut microorganisms before and after the treatment in both groups of patients. Significant differences were observed in the intestinal flora between the two groups. The patients in the study group showed improved immunity after treatment, whereas there was no significant change in the immunity of the control group before and after treatment. However, the difference in progression-free survival between the two groups was not statistically significant. Hyperthermia has a significant impact on improving the microecology of intestinal flora and the immunity of patients, but it does not have a significant effect on prolonging the progression-free survival of patients.

Optical bistability in a heterodimer composed of a quantum dot and a metallic nanoshell.

We theoretically explore the conditions for generating optical bistability (OB) in a heterodimer comprised of a semiconductor quantum dot (SQD) and a metallic nanoshell (MNS). The MNS is made of a metallic nanosphere as a core and a dielectric material as a shell. For the specific hybrid system considered, the bistable effect appears only if the frequency of the pump field is equal to (or slightly less than) the exciton frequency for a proper shell thickness. Bistability phase diagrams, when plotted, show that the dipole-induced bistable region can be greatly broadened by changing the shell thickness of the MNS in a strong exciton-plasmon coupling regime. In particular, we demonstrate that the multipole polarization not only narrows the bistable zone but also enlarges the corresponding thresholds for a given intermediate scaled pumping intensity. On the other hand, when the SQD couples strongly with the MNS, the multipole polarization can also significantly broaden the bistable region and induce a great suppression of the FWM (four-wave mixing) signal for a fixed shell thickness. These interesting findings offer a fresh understanding of the bistability conditions in an SQD/MNS heterodimer, and may be useful in the fabrication of high-performance and low-threshold optical bistable nanodevices.

Case Report: Long-term remission of malignant pleural and peritoneal effusion in a case of advanced lung adenocarcinoma treated with combined crizotinib and anlotinib therapy.

Malignant pleural and peritoneal effusion are common clinical manifestations in advanced malignant tumors, associated with a poor prognosis. This article presents a case of advanced lung adenocarcinoma with ROS1 rearrangement, characterized by persistent malignant pleural and peritoneal effusion. The patient received combined therapy of Crizotinib and Anlotinib, resulting in a significant reduction and even disappearance of the malignant effusion. Exploratory use of this treatment approach improved the patient's quality of life and holds potential for extending overall survival. However, given the single case report nature, the efficacy of this regimen in treating advanced ROS1-rearranged lung adenocarcinoma should be considered as a supplementary strategy, warranting further validation through multicenter clinical data.