Relationship between benefit finding and volunteer motivation among nursing students: The mediating role of perceived social support.

BACKGROUND: Volunteer motivation is essential to advancing community service, education, and career development of nursing students. However, few studies have been conducted on nursing students' volunteer motivation. OBJECTIVES: To investigate the relationship between social support benefit finding and volunteer motivation among nursing students and the role of social support in these relationships. METHOD: This study adopted a descriptive cross-sectional design. A total of 2166 nursing students were recruited from eighteen medical schools in Henan Province, China. Participants completed a sociodemographic questionnaire, the Social Support Scale, the Benefit Finding Scale, and the Volunteer Motivation Scale online between March and May 2022. Correlation and mediation analyses were used to explore the mediating role of social support in the relationships among social support, benefit finding, and volunteer motivation. RESULTS: A total of 2166 valid questionnaires were collected in this study. Benefit finding positively affected volunteer motivation (ß = 0.422, p < 0.01), and perceived social support positively affected volunteer motivation (ß = 0.407, p < 0.01). Perceived social support played a mediating role between benefit finding and volunteer motivation (ß = 0.112, 95 % confidence interval 0.076, 0.148). CONCLUSIONS: The study provides evidence on the mechanisms of action between benefit finding and volunteer motivation among nursing students. Professionals in schools and voluntary organizations should prioritize guiding nursing students to explore the motivations behind volunteering while also fostering a supportive environment for student volunteers in nursing.

Ru-catalyzed asymmetric hydrogenation of α,ß-unsaturated ketones via a hydrogenation/isomerization cascade.

Ru-catalyzed asymmetric hydrogenation of α-substituted α,ß-unsaturated ketones has been developed for the enantioselective synthesis of chiral α-substituted secondary alcohols with high diastereo- and enantioselectivities (up to >99 : 1 dr, 98% ee). Mechanistic experiments suggest that the reaction proceeds via a Ru-catalyzed asymmetric hydrogenation of the CO bond in concert with a base-promoted allylic alcohol isomerization, and the final stereoselectivities were controlled by a DKR process during the asymmetric hydrogenation of the ketone intermediate.

Pan-cancer analysis of NUP155 and validation of its role in breast cancer cell proliferation, migration, and apoptosis.

NUP155 is reported to be correlated with tumor development. However, the role of NUP155 in tumor physiology and the tumor immune microenvironment (TIME) has not been previously examined. This study comprehensively investigated the expression, immunological function, and prognostic significance of NUP155 in different cancer types. Bioinformatics analysis revealed that NUP155 was upregulated in 26 types of cancer. Additionally, NUP155 upregulation was strongly correlated with advanced pathological or clinical stages and poor prognosis in several cancers. Furthermore, NUP155 was significantly and positively correlated with DNA methylation, tumor mutational burden, microsatellite instability, and stemness score in most cancers. Additionally, NUP155 was also found to be involved in TIME and closely associated with tumor infiltrating immune cells and immunoregulation-related genes. Functional enrichment analysis revealed a strong correlation between NUP155 and immunomodulatory pathways, especially antigen processing and presentation. The role of NUP155 in breast cancer has not been examined. This study, for the first time, demonstrated that NUP155 was upregulated in breast invasive carcinoma (BRCA) cells and revealed its oncogenic role in BRCA using molecular biology experiments. Thus, our study highlights the potential value of NUP155 as a biomarker in the assessment of prognostic prediction, tumor microenvironment and immunotherapeutic response in pan-cancer.

A Fast and Efficient Approach to Strength Prediction for Carbon/Epoxy Composites with Resin-Missing Defects.

A novel method is proposed to quickly predict the tensile strength of carbon/epoxy composites with resin-missing defects. The univariate Chebyshev prediction model (UCPM) was developed using the dimension reduction method and Chebyshev polynomials. To enhance the computational efficiency and reduce the manual modeling workload, a parameterization script for the finite element model was established using Python during the model construction process. To validate the model, specimens with different defect sizes were prepared using the vacuum assistant resin infusion (VARI) process, the mechanical properties of the specimens were tested, and the model predictions were analyzed in comparison with the experimental results. Additionally, the impact of the order (second-ninth) on the predictive accuracy of the UCPM was examined, and the performance of the model was evaluated using statistical errors. The results demonstrate that the prediction model has a high prediction accuracy, with a maximum prediction error of 5.20% compared to the experimental results. A low order resulted in underfitting, while increasing the order can improve the prediction accuracy of the UCPM. However, if the order is too high, overfitting may occur, leading to a decrease in the prediction accuracy.

Efficacy of Sevoflurane and Propofol Anesthesia on Perioperative Adverse Cardiovascular Events and Hemodynamics in Elderly Patients With Diabetes.

PURPOSE: This study was undertaken to compare the effects of sevoflurane and propofol anesthesia on perioperative hemodynamics and perioperative adverse cardiovascular events (PACE) in elderly patients with diabetes undergoing general anesthesia for noncardiac surgery. METHODS: According to the random number table (n = 40), 80 patients with diabetes undergoing noncardiac general anesthesia were divided into a control group and an observation group. In the control group, the patients were given propofol 4 to 6 mg/(kg·h), continuously pumped to maintain anesthesia. In the observation group, the patients were given maintained concentration of sevoflurane for 1 to 1.5 minimum alveolar concentration (MAC) for continuous inhalation, while remifentanil with volume fraction of 0.05 to 1 µg/(kg·min) was given for continuous pumping in both groups. The heart rate (HR) and mean arterial pressure (MAP) of the patients were recorded, and the serum creatine kinase-MB (CK-MB) and cardiac troponin I (cTnI) contents before anesthesia (T0), immediately after surgery (T3), and 24 hours later (T4) as well as the blood glucose levels at T0 and T3 were compared between the two groups. The occurrence of PACE in the two groups was compared during the perioperative period. FINDINGS: The HR and MAP 5 minutes after intubation (T1), 1 hour after skin incision (T2), and at T3 in the two groups were significantly lower than those of T0 (P < 0.05), whereas the MAP and HR of T1, T2, and T3 in the observation group were significantly higher than those of the control group (P < 0.05). The T3 blood glucose levels were significantly higher in the two groups than that in T0 (P < 0.05), and the T3 blood glucose levels in the observation group were significantly lower than that in the control group (P < 0.05). CK-MB and cTnI in the two groups were significantly higher at T3 and T4 than T0 (P < 0.05), whereas CK-MB and cTnI in the observation group were significantly lower than in the control group at T3 and T4 (P < 0.05). The incidence of hypotension and PACE was significantly lower in the observation group than in the control group (P < 0.05). IMPLICATIONS: Compared with propofol IV general anesthesia, sevoflurane inhalation anesthesia can improve perioperative hemodynamics stability and reduce the incidence of PACE in elderly patients with diabetes undergoing noncardiac surgery.

Exfoliation of Metal-Organic Frameworks to Give 2D MOF Nanosheets for the Electrocatalytic Oxygen Evolution Reaction.

The structure and properties of materials are determined by a diverse range of chemical bond formation and breaking mechanisms, which greatly motivates the development of selectively controlling the chemical bonds in order to achieve materials with specific characteristics. Here, an orientational intervening bond-breaking strategy is demonstrated for synthesizing ultrathin metal-organic framework (MOF) nanosheets through balancing the process of thermal decomposition and liquid nitrogen exfoliation. In such approach, proper thermal treatment can weaken the interlayer bond while maintaining the stability of the intralayer bond in the layered MOFs. And the following liquid nitrogen treatment results in significant deformation and stress in the layered MOFs' structure due to the instant temperature drop and drastic expansion of liquid N2, leading to the curling, detachment, and separation of the MOF layers. The produced MOF nanosheets with five cycles of treatment are primarily composed of nanosheets that are less than 10 nm in thickness. The MOF nanosheets exhibit enhanced catalytic performance in oxygen evolution reactions owing to the ultrathin thickness without capping agents which provide improved charge transfer efficiency and dense exposed active sites. This strategy underscores the significance of orientational intervention in chemical bonds to engineer innovative materials.

Effect of Resin-Missing Defects on Tensile Behavior of Carbon Fiber/Epoxy Composites.

This study explores the impact of resin-missing defects on the mechanical properties of composite laminates through experimental and finite element methods. Specimens with varying defect contents (5.3%, 8.0%, 10.7%, 13.3%, and 16.7%) were prepared via Vacuum Assistant Resin Infusion process. Experimental tests were conducted with the assistance of Digital Image Correlation measurements to illustrate the impact of resin-missing defects on failure characteristics. The experimental results indicate that the existence of resin-missing defects altered the stress distribution, increased the local stress, and reduced the tensile strength of the composite laminate. The DIC results indicate that the presence of defects weakens the matrix, leading to premature damage and deterioration. Numerical modeling with a progressive damage analysis method was developed to simulate the failure process and the influence of the resin-missing defects. The simulation results agree well with the experimental results, and the maximum error was 3.06%. The failure modes obtained from finite elements are consistent with the experimental and DIC results. Furthermore, a study was conducted on how the location of resin-missing defects affects the mechanical properties of composite laminates. The findings suggest that defects situated at the edges or on the surface of the material have a more significant impact on the tensile strength.

Quantitative analysis of molecular transport in the extracellular space using physics-informed neural network.

The brain extracellular space (ECS), an irregular, extremely tortuous nanoscale space located between cells or between cells and blood vessels, is crucial for nerve cell survival. It plays a pivotal role in high-level brain functions such as memory, emotion, and sensation. However, the specific form of molecular transport within the ECS remain elusive. To address this challenge, this paper proposes a novel approach to quantitatively analyze the molecular transport within the ECS by solving an inverse problem derived from the advection-diffusion equation (ADE) using a physics-informed neural network (PINN). PINN provides a streamlined solution to the ADE without the need for intricate mathematical formulations or grid settings. Additionally, the optimization of PINN facilitates the automatic computation of the diffusion coefficient governing long-term molecule transport and the velocity of molecules driven by advection. Consequently, the proposed method allows for the quantitative analysis and identification of the specific pattern of molecular transport within the ECS through the calculation of the Péclet number. Experimental validation on two datasets of magnetic resonance images (MRIs) captured at different time points showcases the effectiveness of the proposed method. Notably, our simulations reveal identical molecular transport patterns between datasets representing rats with tracer injected into the same brain region. These findings highlight the potential of PINN as a promising tool for comprehensively exploring molecular transport within the ECS.

Prognostic value analysis of cholesterol and cholesterol homeostasis related genes in breast cancer by Mendelian randomization and multi-omics machine learning.

Introduction: The high incidence of breast cancer (BC) prompted us to explore more factors that might affect its occurrence, development, treatment, and also recurrence. Dysregulation of cholesterol metabolism has been widely observed in BC; however, the detailed role of how cholesterol metabolism affects chemo-sensitivity, and immune response, as well as the clinical outcome of BC is unknown. Methods: With Mendelian randomization (MR) analysis, the potential causal relationship between genetic variants of cholesterol and BC risk was assessed first. Then we analyzed 73 cholesterol homeostasis-related genes (CHGs) in BC samples and their expression patterns in the TCGA cohort with consensus clustering analysis, aiming to figure out the relationship between cholesterol homeostasis and BC prognosis. Based on the CHG analysis, we established a CAG_score used for predicting therapeutic response and overall survival (OS) of BC patients. Furthermore, a machine learning method was adopted to accurately predict the prognosis of BC patients by comparing multi-omics differences of different risk groups. Results: We observed that the alterations in plasma cholesterol appear to be correlative with the venture of BC (MR Egger, OR: 0.54, 95% CI: 0.35-0.84, p<0.006). The expression patterns of CHGs were classified into two distinct groups(C1 and C2). Notably, the C1 group exhibited a favorable prognosis characterized by a suppressed immune response and enhanced cholesterol metabolism in comparison to the C2 group. In addition, high CHG score were accompanied by high performance of tumor angiogenesis genes. Interestingly, the expression of vascular genes (CDH5, CLDN5, TIE1, JAM2, TEK) is lower in patients with high expression of CHGs, which means that these patients have poorer vascular stability. The CAG_score exhibits robust predictive capability for the immune microenvironment characteristics and prognosis of patients(AUC=0.79). It can also optimize the administration of various first-line drugs, including AKT inhibitors VIII Imatinib, Crizotinib, Saracatinib, Erlotinib, Dasatinib, Rapamycin, Roscovitine and Shikonin in BC patients. Finally, we employed machine learning techniques to construct a multi-omics prediction model(Risklight),with an area under the feature curve (AUC) of up to 0.89. Conclusion: With the help of CAG_score and Risklight, we reveal the signature of cholesterol homeostasis-related genes for angiogenesis, immune responses, and the therapeutic response in breast cancer, which contributes to precision medicine and improved prognosis of BC.

Discovery of novel potent PI3K/mTOR dual-target inhibitors based on scaffold hopping: Design, synthesis, and antiproliferative activity.

The PI3K/AKT/mTOR pathway is one of the most common dysregulated signaling cascade responses in human cancers, playing a crucial role in cell proliferation and angiogenesis. Therefore, the development of anticancer drugs targeting the PI3K and mTOR pathways has become a research hotspot in cancer treatment. In this study, the PI3K selective inhibitor GDC-0941 was selected as a lead compound, and 28 thiophenyl-triazine derivatives with aromatic urea structures were synthesized based on scaffold hopping, serving as a novel class of PI3K/mTOR dual inhibitors. The most promising compound Y-2 was obtained through antiproliferative activity evaluation, kinase inhibition, and toxicity assays. The results showed that Y-2 demonstrated potential inhibitory effects on both PI3K kinase and mTOR kinase, with IC50 values of 171.4 and 10.2 nM, respectively. The inhibitory effect of Y-2 on mTOR kinase was 52 times greater than that of the positive drug GDC-0941. Subsequently, the antitumor activity of Y-2 was verified through pharmacological experiments such as AO staining, cell apoptosis, scratch assays, and cell colony formation. The antitumor mechanism of Y-2 was further investigated through JC-1 experiments, real-time quantitative PCR, and Western blot analysis. Based on the above experiments, Y-2 can be identified as a potent PI3K/mTOR dual inhibitor for cancer treatment.

Optical microscopic study on a novel morphological classification method of multiple diagnostic features of Sarcoptes scabiei var. hominis.

Optical microscopy is the gold standard technique used to confirm the diagnosis of scabies. Multiple diagnostic features of the pathogen Sarcoptes scabiei var. hominis (S. scabiei) can be identified under a microscope and classified into 3 categories: mites, eggs and fecal pellets. However, mite and eggshell fragments can also be observed, which have been ignored in the 2020 International Alliance for the Control of Scabies (IACS) Criteria and by most researchers. In this study, we propose a novel morphological classification method that classifies multiple diagnostic features into 5 categories and 7 subcategories. Our results revealed that 65.2% (1893 of 2896) of the positive cases were confirmed through the identification of mites, eggs or fecal pellets, whereas up to 34.6% (1003 of 2896) of the positive cases were confirmed through the identification of mite or eggshell fragments. Therefore, the important diagnostic values of mite and eggshell fragments should be emphasized. Importantly, for the first time, mite and eggshell fragments were classified into 7 subcategories, some of which are easily ignored or confused with contaminating artefacts. We believe that this novel morphological classification method will be beneficial for operator training in interpreting slides and in improving the 2020 IACS Criteria.

Depression score mediate the association between a body shape index and infertility in overweight and obesity females, NHANES 2013-2018.

BACKGROUND: Overweight and obese females demonstrate a significantly increased risk of anovulatory infertility. This study aims to investigate whether depression score could mediate the association between a body shape index (ABSI) and infertility, especially in overweight and obese population. METHODS: We included 5431 adult female Americans from the National Health and Nutrition Examination Survey (NHANES, 2013-2018) database. ABSI manifested the body shape using waist circumference, weight, and height. Infertility or fertility status was defined by interviewing female participants aged ≥ 18 through the reproductive health questionnaires. Depression symptoms were assessed using the Patient Health Questionnaire-9 (PHQ-9) with total scores between 0 and 27. To investigate the association of infertility with ABSI and other individual components, survey-weighted multivariable logistic regression was performed. Mediation analysis of PHQ-9 score was conducted to disentangle the pathways that link ABSI to infertility among the NHANES participants. RESULTS: 596 (10.97%) females were categorized with having infertility among 5431 participants. Participants with infertility showed higher ABSI and PHQ-9 score, appearing greater population proportion with depression symptoms. In the multivariable logistic regression model, ABSI (adjusted odds ratio = 0.14, 95% CI: 0.04 to 0.50) and PHQ-9 (adjusted odds ratio = 1.04, 95% CI: 1.01 to 1.07) were positively associated with infertility. PHQ-9 score was estimated to mediate 0.2% (P = 0.03) of the link between ABSI and infertility in all individuals, but to mediate 13.5% (P < 0.01) of the ABSI-infertility association in overweight and obese adult females. CONCLUSION: The association between ABSI and infertility seems to be mediated by depression symptoms scored by PHQ-9, especially in those adult females with overweigh and obesity. Future studies should be implemented to further explore this mediator in ABSI-infertility link.

Brain-derived neurotrophic factor and nerve growth factor expression in endometriosis: A systematic review and meta-analysis.

Endometriosis is diagnosed by laparoscopic surgery. The availability of biomarkers can help understand the pathophysiology and aid in the diagnosis of the condition. In this context, this review aimed to examine levels of expression of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) are increased amongst patients with endometriosis and if they can serve as a potential biomarker. PubMed, CENTRAL, Scopus, Web of Science, and Embase databases were searched for studies comparing BDNF or NGF levels amongst endometriosis patients and controls. Data were pooled for serum and tissue levels of BDNF and NGF. Ten fulfilled the inclusion criteria. On comparing BDNF levels, it was noted that endometrial tissue had significantly higher expression of BDNF levels as compared to controls (SMD: 1.73 95% CI: 0.64, 2.82 I2 = 89%). Similarly, the meta-analysis found significantly higher serum levels of BDNF in endometriosis patients as compared to controls (SMD: 1.66 95% CI: 0.73, 2.59 I2 = 95%). Pooled analysis showed significantly increased levels of NGF in endometrial tissue as compared to controls (SMD: 4.15 95% CI: 0.11, 8.18 I2 = 98%) but with unstable results on sensitivity analysis. Only one study showed higher levels of NGF in serum amongst endometriosis patients. Limited data shows higher expression of BDNF in endometrial lesions and increased serum levels of BDNF in endometriosis patients. Similar results were noted for NGF but with very scarce data. Further research is needed to establish BDNF and NGF as suitable biomarkers for the disease.

Rapid Crystallization and Fluorescence of Poly(ethylene terephthalate) Using Graphene Quantum Dots as Nucleating Agents.

In this study, graphene quantum dots (GQDs) with a diameter of ~3 nm were successfully synthesized and incorporated into a poly(ethylene terephthalate) (PET) matrix to fabricate PET/GQDs nanocomposites. The impact of GQDs on the crystallization and thermal stability of the PET/GQDs nanocomposites was investigated. It was observed that the addition of only 0.5 wt% GQDs into the nanocomposites resulted in a significant increase in the crystallization temperature (peak temperature) of PET, from 194.3 °C to 206.0 °C during the cooling scan process. This suggested that an optimal concentration of GQDs could function as a nucleating agent and effectively enhance the crystallization temperature of PET. The isothermal crystallization method was employed to analyze the crystallization kinetics of the PET/GQDs nanocomposites, and the data showed that 0.5 wt% GQDs significantly accelerated the crystallization rate. Furthermore, the incorporation of GQDs into the PET matrix imparted photoluminescent properties to the resulting PET/GQDs nanocomposites. The PET crystals with GQDs as crystal nuclei and the crazes caused by defects played a vital role in isolating and suppressing the concentration quenching of GQDs. This effect facilitated the detection of defects in PET.

Identifying and ranking causal microbial biomarkers for colorectal cancer at different cancer subsites and stages: a Mendelian randomization study.

Introduction: The gut microbiome is directly involved in colorectal carcinogenesis, but much of the epidemiological evidence for the effect of the gut microbiome on colorectal cancer (CRC) risk comes from observational studies, and it is unclear whether identified microbial alterations are the cause or consequence of CRC development. Methods: Univariate Mendelian randomization (MR) analysis and multivariate MR analysis based on Bayesian model averaging were performed to comprehensively explore the microbial risk factors associated with CRC. The Network Module Structure Shift method was used to identify microbial biomarkers associated with CRC. Mediation analysis was used to explore the dietary habits-microbiota-CRC pathway. Results: The results of the four methods showed that 9 bacteria had a robust causal relationship with the development of CRC. Among them, Streptococcus thermophilus reduced the risk of CRC; Eubacterium ventriosum and Streptococcus were beneficial bacteria of malignant tumors of colon (CC); Erysipelotrichaceae was a protective factor for malignant tumors of rectal (CR); Bacteroides ovatus was a risk factor for benign tumors. Finally, the mediation analysis revealed 10 pathways by which dietary regulation bacteria affected the risk of CRC, including alcohol consumption increased the risk of CC by reducing the abundance of Eubacterium ventriosum (mediated proportion: 43.044%), and the mediated proportion of other pathways was 7.026%-34.22%. Discussion: These findings will contribute to the understanding of the different carcinogenic mechanisms of intestinal flora in the colon and rectum and the risk of tumor transformation, thereby aiding CRC prevention, early screening, and the development of future strategies to reduce CRC risk.

New Function of Metal-Organic Framework: Structurally Ordered Metal Promoter.

The remarkable roles of metal promoters have been known for nearly a century, but it is still a challenge to find a suitable structure model to reveal the action mechanism behind metal promoters. Herein, a new function of metal-organic frameworks (MOFs) is developed as an ideal model to construct structurally ordered metal promoters by a targeted post-modification strategy. MOFs as model not only favor clearing the real action mechanism behind metal promoters, but also can anchor one or multiple kinds of metal promoters especially noble metal promoters. Typically, the as-prepared Pd/bpy-UiO-Cu catalysts show high selectivity (>99%) toward 4-nitrophenylethane in 4-nitrostyrene hydrogenation, mainly due to the enhanced interaction between Pd nanoparticles and MOF carriers induced by Cu promoters, thus inhibiting the hydrogenation of 4-nitrophenylethane. This strategy with flexibility and universality will open up a new route to synthesize efficient catalysts with structurally ordered metal promoters.

EZH2 regulates pancreatic cancer cells through E2F1, GLI1, CDK3, and Mcm4.

Pancreatic cancer (PC) is one of the most common malignant tumors in digestive tract. To explore the role of epigenetic factor EZH2 in the malignant proliferation of PC, so as to provide effective medical help in PC. Sixty paraffin sections of PC were collected and the expression of EZH2 in PC tissues was detected by immunohistochemical assay. Three normal pancreas tissue samples were used as controls. The regulation of EZH2 gene on proliferation and migration of normal pancreatic cell and PC cell were determined by MTS, colony forming, Ki-67 antibody, scratch and Transwell assays. Through differential gene annotation and differential gene signaling pathway analysis, differentially expressed genes related to cell proliferation were selected and verified by RT-qPCR. EZH2 is mainly expressed in the nuclei of pancreatic tumor cells, but not in normal pancreatic cells. The results of cell function experiments showed that EZH2 overexpression could enhance the proliferation and migration ability of PC cell BXPC-3. Cell proliferation ability increased by 38% compared to the control group. EZH2 knockdown resulted in reduced proliferation and migration ability of cells. Compared with control, proliferation ability of cells reduced by 16%-40%. The results of bioinformatics analysis of transcriptome data and RT-qPCR demonstrated that EZH2 could regulate the expression of E2F1, GLI1, CDK3 and Mcm4 in normal and PC cells. The results revealed that EZH2 might regulate the proliferation of normal pancreatic cell and PC cell through E2F1, GLI1, CDK3 and Mcm4.

Epoxy-Modified Bismaleimide Structural Adhesive Film Toughened Synergistically with PEK-C and Core-Shell Polymers for Bonding CFRP.

Bismaleimide (BMI) resin-based structural adhesives have excellent heat resistance, with important applications demonstrated in the bonding of high-temperature BMI composites. In this paper, we report an epoxy-modified BMI structural adhesive with excellent properties for bonding BMI-based CFRP. We prepared the BMI adhesive using epoxy-modified BMI as the matrix and PEK-C and core-shell polymers as synergistic tougheners. We found that the epoxy resins improve the process and bonding properties of BMI resin but slightly reduce thermal stability. PEK-C and core-shell polymers synergistically improve the toughness and bonding performances of the modified BMI adhesive system and allow the maintenance of heat resistance. The optimized BMI adhesive exhibits excellent heat resistance, with a high glass transition temperature of 208.6 °C and a high thermal degradation temperature of 425.4 °C. Most importantly, the optimized BMI adhesive exhibits satisfactory intrinsic bonding and thermal stability. It has a high shear strength of 32.0 MPa at room temperature and up to 17.9 MPa at 200 °C. The BMI adhesive-bonded composite joint has a high shear strength of 38.6 and 17.3 MPa at room temperature and 200 °C, respectively, indicating effective bonding and excellent heat resistance.

ß, ß-Dimethylacrylshikonin potentiates paclitaxel activity, suppresses immune evasion and triple negative breast cancer progression via STAT3Y705 phosphorylation inhibition based on network pharmacology and transcriptomics analysis.

BACKGOUND: Triple negative breast cancer (TNBC) is an extremely aggressive and rapidly progressing cancer, wherein existing therapies provide little benefit to patients. ß, ß-Dimethylacrylshikonin (DMAS), an active naphthoquinone derived from comfrey root, has potent anticancer activity. However, the antitumor function of DMAS against TNBC remains to be proved. PURPOSE: Explore effects of DMAS on TNBC and clarify the mechanism. STUDY DESIGN: Network pharmacology, transcriptomics and various cell functional experiments were applied to TNBC cells to explore the effects of DMAS on TNBC. The conclusions were further validated in xenograft animal models. METHODS: MTT, EdU, transwell, scratch tests, flow cytometry, immunofluorescence, and immunoblot were utilized to assess the activity of DMAS on three TNBC cell lines. The anti-TNBC mechanism of DMAS was clarified by overexpression and knockdown of STAT3 in BT-549 cells. In vivo efficacy of DMAS was analysed using a xenograft mouse model. RESULTS: In vitro analysis revealed that DMAS inhibited the G2/M phase transition and suppressed TNBC proliferation. Additionally, DMAS triggered mitochondrial-dependent apoptosis and reduced cell migration by antagonizing epithelial-mesenchymal transition. Mechanistically, DMAS exerted its antitumour effects by inhibiting STAT3Y705 phosphorylation. STAT3 overexpression abolished the inhibitory effect of DMAS. Further studies showed that treatment with DMAS inhibited TNBC growth in a xenograft model. Notably, DMAS potentiated the sensitivity of TNBC to paclitaxel and inhibited immune evasion by downregulating the immune checkpoint PD-L1. CONCLUSIONS: For the first time, our study revealed that DMAS potentiates paclitaxel activity, suppresses immune evasion and TNBC progression by inhibiting STAT3 pathway. It has the potential as a promising agent for TNBC.

The Interaction between Intratumoral Microbiome and Immunity Is Related to the Prognosis of Ovarian Cancer.

Microbiota can influence the occurrence, development, and therapeutic response of a wide variety of cancer types by modulating immune responses to tumors. Recent studies have demonstrated the existence of intratumor bacteria inside ovarian cancer (OV). However, whether intratumor microbes are associated with tumor microenvironment (TME) and prognosis of OV still remains unknown. The RNA-sequencing data and clinical and survival data of 373 patients with OV in The Cancer Genome Atlas (TCGA) were collected and downloaded. According to the knowledge-based functional gene expression signatures (Fges), OV was classified into two subtypes, termed immune-enriched and immune-deficient subtypes. The immune-enriched subtype, which had higher immune infiltration enriched with CD8+ T cells and the M1 type of macrophages (M1) and higher tumor mutational burden, exhibited a better prognosis. Based on the Kraken2 pipeline, the microbiome profiles were explored and found to be significantly different between the two subtypes. A prediction model consisting of 32 microbial signatures was constructed using the Cox proportional-hazard model and showed great prognostic value for OV patients. The prognostic microbial signatures were strongly associated with the hosts' immune factors. Especially, M1 was strongly associated with five species (Achromobacter deleyi and Microcella alkaliphila, Devosia sp. strain LEGU1, Ancylobacter pratisalsi, and Acinetobacter seifertii). Cell experiments demonstrated that Acinetobacter seifertii can inhibit macrophage migration. Our study demonstrated that OV could be classified into immune-enriched and immune-deficient subtypes and that the intratumoral microbiota profiles were different between the two subtypes. Furthermore, the intratumoral microbiome was closely associated with the tumor immune microenvironment and OV prognosis. IMPORTANCE Recent studies have demonstrated the existence of intratumoral microorganisms. However, the role of intratumoral microbes in the development of ovarian cancer and their interaction with the tumor microenvironment are largely unknown. Our study demonstrated that OV could be classified into immune-enriched and -deficient subtypes and that the immune enrichment subtype had a better prognosis. Microbiome analysis showed that intratumor microbiota profiles were different between the two subtypes. Furthermore, the intratumor microbiome was an independent predictor of OV prognosis that could interact with immune gene expression. Especially, M1 was closely associated with intratumoral microbes, and Acinetobacter seifertii could inhibit macrophage migration. Together, the findings of our study highlight the important roles of intratumoral microbes in the TME and prognosis of OV, paving the way for further investigation into its underlying mechanisms.