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Inhibitor of apoptosis proteins (IAPs) are crucial components of apoptosis that perform vital roles in the regulation of caspase activity in organisms. In this study, two IAPs genes were identified from Cotesia chilonis, the dominant parasitic wasp of Chilo suppressalis. CcIAP1 gene is a typical IAP and contains two BIR domains and a RING domain, whereas CcIAP gene is an atypical IAP1 only containing two BIR domains. Phylogenetic analysis indicated that CcIAP1 and CcIAP were grouped with other Hymenopteran IAPs and IAP1 in C. suppressalis. Real-time quantitative PCR revealed that CcIAP1 and CcIAP genes were both highly induced at −6°C and 30°C, and expression was highest at the third instar stage. The expression of CcIAP1 and CcIAP genes were significantly induced during parasitism of C. suppressalis, and the 7-d time point resulted in the highest expression levels for both genes, in which was an advanced stage of larval development of C. chilonis. RNAi experiments showed that CcIAP1 gene was the key IAP in the regulation of apoptosis of C. chilonis and its host. In conclusion, CcIAP1 and CcIAP correlate with the development of C. chilonis and their responses to temperature stress.

Background: Tumor antigenicity and efficiency of antigen presentation jointly influence tumor immunogenicity, which largely determines the effectiveness of immune checkpoint blockade (ICB). However, the role of altered antigen processing and presentation machinery (APM) in breast cancer (BRCA) has not been fully elucidated. Methods: A series of bioinformatic analyses and machine learning strategies were performed to construct APM-related gene signatures to guide personalized treatment for BRCA patients. A single-sample gene set enrichment analysis (ssGSEA) algorithm and weighted gene co-expression network analysis (WGCNA) were combined to screen for BRCA-specific APM-related genes. The non-negative matrix factorization (NMF) algorithm was used to divide the cohort into different clusters and the fgsea algorithm was applied to investigate the altered signaling pathways. Random survival forest (RSF) and the least absolute shrinkage and selection operator (Lasso) Cox regression analysis were combined to construct an APM-related risk score (APMrs) signature to predict overall survival. Furthermore, a nomogram and decision tree were generated to improve predictive accuracy and risk stratification for individual patients. Based on Tumor Immune Dysfunction and Exclusion (TIDE) method, random forest (RF) and Lasso logistic regression model were combined to establish an APM-related immunotherapeutic response score (APMis). Finally, immune infiltration, immunomodulators, mutational patterns, and potentially applicable drugs were comprehensively analyzed in different APM-related risk groups. IHC staining was used to assess the expression of APM-related genes in clinical samples. Results: In this study, APMrs and APMis showed favorable performances in risk stratification and therapeutic prediction for BRCA patients. APMrs exhibited more powerful prognostic capacity and accurate survival prediction compared to conventional clinicopathological features. APMrs was closely associated with distinct mutational patterns, immune cell infiltration and immunomodulators expression. Furthermore, the two APM-related gene signatures were independently validated in external cohorts with prognosis or immunotherapeutic responses. Potential applicable drugs and targets were mined in the APMrs-high group. APM-related genes were further validated in our in-house samples. Conclusion: The APM-related gene signatures established in our study could improve the personalized assessment of survival risk and guide ICB decision-making for BRCA patients.

Abstract Background The metastasis of breast cancer (BC) is a complex multi-step pathological process, strictly dependent on the intrinsic characteristics of BC cells and promoted by a predisposing microenvironment. Although immunotherapy has made important progress in metastasis BC, the heterogeneity of PD-L1 in tumor associated macrophages (TAMs) in BC and the underlying mechanisms in the metastasis development of BC are still not completely elucidated. Small extracellular vesicles (sEVs) represent essential interaction mediators between BC cells and TAMs. It is worth noting to explore the underlying mechanisms typical of sEVs and their role in the metastasis development of BC. Methods The structure of sEVs was identified by TEM, while the particle size and amounts of sEVs were detected by BCA and NTA analysis. The specific PD-L1 + CD163 + TAM subpopulation in metastasis BC was identified by scRNA-seq data of GEO datasets and verified by IHC and IF. The function of TAMs and sEVs in metastasis BC was explored by RT-qPCR, WB, IF, flow cytometry and in vivo experiment. The expression profiles of plasma sEVs-miRNA in relation to BC metastasis was analyzed using next-generation sequencing. Further detailed mechanisms of sEVs in the metastasis development of BC were explored by bioinformatics analysis, RT-qPCR, WB and luciferase reporter assay. Results In this study, we identified that the immunosuppressive molecule PD-L1 was more abundant in TAMs than in BC cells, and a specific PD-L1 + CD163 + TAM subpopulation was found to be associated with metastasis BC. Additionally, we found that BC cells-derived sEVs can upregulate the PD-L1 expression and induce the M2 polarization, enhancing the metastasis development both in vitro and in vivo. Also, Clinical data showed that sEV-miR-106b-5p and sEV-miR-18a-5p was in relation to BC metastasis development and poor prognosis of BC patients. Further mechanistic experiments revealed that BC-derived sEV-miR-106b-5p and sEV-miR-18a-5p could synergistically promoted the PD-L1 expression in M2 TAMs by modulating the PTEN/AKT and PIAS3/STAT3 pathways, resulting in the enhancement of the BC cells invasion and metastasis. Conclusions Our study demonstrated that BC-derived sEVs can induce metastasis in BC through miR-106b-5p/PTEN/AKT/PD-L1 and miR-18a-5p/PIAS3/STAT3/PD-L1 pathways in TAMs. Therefore, the inhibition of these specific interactions of signaling pathways would represent a promising target for future therapeutic strategies for treatment of BC.

Abstract Colorectal cancer (CRC) is a common gastrointestinal malignancy with high morbidity and fatality. Chemotherapy, as traditional therapy for CRC, has exerted well antitumor effect and greatly improved the survival of CRC patients. Nevertheless, chemoresistance is one of the major problems during chemotherapy for CRC and significantly limits the efficacy of the treatment and influences the prognosis of patients. To overcome chemoresistance in CRC, many strategies are being investigated. Here, we review the common and novel measures to combat the resistance, including drug repurposing (nonsteroidal anti‐inflammatory drugs, metformin, dichloroacetate, enalapril, ivermectin, bazedoxifene, melatonin, and S‐adenosylmethionine), gene therapy (ribozymes, RNAi, CRISPR/Cas9, epigenetic therapy, antisense oligonucleotides, and noncoding RNAs), protein inhibitor (EFGR inhibitor, S1PR2 inhibitor, and DNA methyltransferase inhibitor), natural herbal compounds (polyphenols, terpenoids, quinones, alkaloids, and sterols), new drug delivery system (nanocarriers, liposomes, exosomes, and hydrogels), and combination therapy. These common or novel strategies for the reversal of chemoresistance promise to improve the treatment of CRC.

Abstract Purpose To investigate the mechanism underlying the modulation of M1 macrophage polarization by exosomes released from hyperthermia-treated triple-negative breast cancer (TNBC) cells. Materials and methods In this study, the effects of hyperthermia on TNBC cells were examined using cell counting kit-8, apoptosis, and cell cycle assays. Transmission electron microscopy was used to identify the structure of exosomes, while bicinchoninic acid and nanoparticle tracking analysis were used to detect particle size and amounts of exosomes released after hyperthermia. The polarization of macrophages incubated with exosomes derived by hyperthermia-pretreated TNBC cells were assessed by RT-qPCR and flow cytometry analysis. Next, RNA sequencing was performed to determine the targeting molecules changed in hyperthermia-treated TNBC cells in vitro. Finally, the mechanism underlying the modulation of macrophage polarization by exosomes derived from hyperthermia-treated TNBC cells was examined by using RT-qPCR, immunofluorescence and flow cytometry analysis. Results Hyperthermia markedly reduced cell viability in TNBC cells and promoted the secretion of TNBC cell-derived exosomes. The hub genes of hyperthermia-treated TNBC cells were significantly correlated with macrophage infiltration. Additionally, hyperthermia-treated TNBC cell-derived exosomes promoted M1 macrophage polarization. Furthermore, the expression levels of heat shock proteins, including HSPA1A, HSPA1B, HSPA6, and HSPB8, were significantly upregulated upon hyperthermia treatment, with HSPB8 exhibiting the highest upregulation. Moreover, hyperthermia can induce M1 macrophage polarization by promoting exosome-mediated HSPB8 transfer. Conclusion This study demonstrated a novel mechanism that hyperthermia can induce M1 polarization of macrophages via exosome-mediated HSPB8 transfer. These results will help with future development of an optimized hyperthermia treatment regime for clinical application, especially for combination treatment with immunotherapy.

Background: This study aimed to assess the clinical significance of generating a volumetric stent expansion index for tapering lesions through intravascular ultrasound (IVUS). Previous IVUS studies have used minimal stent area (MSA) to predict adverse outcomes. Methods: A total of 251 tapering lesions were treated in this study via IVUS guidance in 232 patients. Eight stent expansion indices were evaluated to determine the association of these indices with device-oriented clinical endpoints (DoCEs) after two-year follow-ups. These were the ILUMIEN III and IV standards, the ULTIMATE (Intravascular Ultrasound Guided Drug Eluting Stents Implantation in “All-Comers” Coronary Lesions) standard, the IVUS-XPL (Impact of Intravascular Ultrasound Guidance on the Outcomes of Xience Prime Stents in Long Lesions) standard, the minimal volumetric expansion index (MVEI) using the Huo-Kassab or linear model, the MSA/vessel area at the MSA cross-section, the traditional stent expansion (MSA/mean proximal and distal reference lumen cross-sectional area), and MSA. Results: The MVEI was the only stent expansion index that correlated significantly with the two-year DoCEs (hazard ratio [HR], 1.91; 95% confidence interval [CI]: 1.16–3.96; p = 0.028). In the ROC analysis, the area under the curve for the MVEI was 0.71 (p = 0.002), with an optimal cut-off value of 62.2 for predicting the DoCEs. Conclusions: This is the first study to use IVUS for tapering lesions and demonstrate that the MVEI is an independent predictor of two-year DoCEs.

Abstract Objective To explore the influence and the underlying mechanism of vaspin (visceral adipose tissue‐derived serpin) on the development of triple‐negative breast malignancy. Methods First, we analyzed medical records and screened out 22 breast cancer patients with different BMI according to inclusion and exclusion criterion, and measured serum vaspin of those patients. Then we studied the effects of vaspin on TNBC cell lines by using EdU assay, colony formation, transwell and wound‐healing assay. Later, we used bioinformatics analysis to identify downstream effectors and verify with qRT‐PCR, luciferase assay, western blot, etc. Results We found the vaspin level was positively correlated with BMI in breast malignant patients and vaspin could significantly enhance the proliferation, infiltration and transferring of triple‐negative breast cancer cells by restraining the expression of miR‐33a‐5p. By using bioinformatic analysis and luciferase assay, we identified miR‐33a‐5p directly regulating ABHD2. Conclusion Vaspin, as a cancer‐promoting cytokine, may inhibit miR‐33a‐5p thus increasing the level of ABHD2 to promote the development of the triple‐negative breast cancer.

IoT device market has grown rapidly in recent years, with many researches have been done to investigate the IoT devices’ adoption factors. However, it is crucial to understand how to maintain the users’ continuance intention. This study, based on the post-acceptance model of the Expectation Confirmation Model (ECM), investigates the impact of early-stage users’ personal traits (personal innovativeness), social influence (normative and informational), and familiarity, on the social diffusion of IoT devices (in particular, smart speakers) measured by the continuation intention of smart speakers. We tested the research model and hypotheses using data from 364 smart speaker users, analyzed with partial least square technique using Smart-PLS. The data analysis results revealed that satisfaction has a very strong and positive impact on continuance intention. Perceived usefulness, confirmation, and personal innovativeness are positively associated with continuance intention via satisfaction. Social influence, represented by normative and informational social influence, showed a significant positive impact on continuance intention, a high degree of familiarity weakens the influence of normative social influence on continuance intention; however, familiarity has no impact on the relationship between informational social influence and continuance intention.

This paper mainly focuses on the impact of inclined static air gap eccentricity (ISAGE) on the electromagnetic characteristics and mechanical performances (vibration, deformation, strain and stress). Considering different ISAGE fault types in the theoretical and finite element analysis (FEA) model of synchronous generators, the effects of intersection position of the rotor center axis and stator center axis, rotor inclined angle, and the combination of the previous two fault types on MFD, phase current and radial magnetic pulling per unit area (MPPUA) are analyzed and compared. Then, based on the stator model used uniformly in three physical fields, the harmonic response and mechanical response are investigated with loads imported by the electromagnetic field. Finally, the stator radial vibration measurement experiments are carried out to verify the results obtained by theoretical analysis and FEA. It is shown that ISAGE will considerably enlarge the fluctuation of MPPUA and intensify the radial vibration of the stator, especially at the 2nd harmonic. The probability of failure at tooth tip and inner slot wall of the stator will increase.

Abstract To minimize surgical complications and staged procedures halo-traction is often used during deformity corrections. But the use of halo-traction in the treatment of refractory cervical kyphosis secondary to infections has never been reported. This study investigated the role of halo-traction in the treatment of cervical infection patients associated with refractory kyphosis. We retrospectively reviewed 48 patients with cervical infection associated with refractory kyphosis who were treated in our spine department. Patients were divided into two groups, the traction group (A) and the non-traction group (B). Group A underwent preoperative halo-traction followed by surgery, while group B underwent surgery alone. Between the two groups, we analyzed the kyphosis deformity correction, level of fusions, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), functional improvement by Neck disability index (NDI) score, and complications. Group A had a better correction of kyphosis deformity compared to group B (27.01 ± 11.54)0 versus (18.08 ± 10.04)0 (P = 0.01, Z = − 2.44). No statistically significant differences between the two groups in terms of functional improvement, level of fusions, ESR and CRP. Group B had 3 revision surgery cases. Preoperative halo-traction followed by surgery is superior in kyphosis correction in the treatment of patients with cervical infections with refractory kyphosis.

For the problem that how the grouting reinforcement of a single penetrated structural plane affects the bearing capacity of surrounding rock, an approach of rock samples preparation with single penetrated fracture surface is proposed firstly, and the rock samples are injected with ultrafine cement and epoxy resin, respectively. Then, the strength and deformation characteristics of the consolidated body under uniaxial (triaxial) compression are investigated with the RMT-150C experimental system. Finally, the micro consolidation mechanism of structural plane grouting is revealed using theoretical analysis and electron microscope scanning. It is found that the fracture surface generated under the triaxial loading-unloading condition is closer to the engineering practice and meets the experimental requirements. The stress−strain characteristic curves of the specimens injected with ultrafine cement show phased deformation characteristics, and the curves of the specimens injected with epoxy resin are relatively smooth. For the strength characteristics, the influence of confining pressure is significantly larger than that of grouting material selection. Grouting reinforcement can improve the residual strength of rock mass. With the increase of confining pressure, the increase of improvement coefficient of residual strength is less obvious, and the peak strength of the consolidated body is closer to that of intact rock. For the failure characteristics, the main fracture surface of the specimen injected with ultrafine cement shears and slips along the original fracture surface, and the main fracture surface of the specimen injected with epoxy resin is a new penetrated fracture surface. Finally, based on the Mohr-Coulomb criterion, the relationship between the bonding force of grouting materials and the strength improvement coefficient of structural plane is established. It is found that the strength improvement coefficient of structural plane has a linear relationship with the bonding force of grout. The comparison between the calculation and test results shows that the formula is reasonable and can provide a reference for the optimization of deep surrounding rock support.

AIM: To prepare a folic acid-magnetic dual target, adriamycin(ADM)-loaded phase change liposome nanoparticles(FA-PFH-Fe3O4@ADM), and observe its ability to target retinoblastoma Y79 cells and its three-mode imaging ability of in vitro ultrasound/photoacoustic/magnetic resonance.METHODS: FA-PFH-Fe3O4@ADM was prepared by the double emulsification method, and its basic characteristics were tested. Test the cellular safety of nanoparticles. Observe the heating phenomenon and phase transition of nanoparticles under 808nm laser. Y79 cells in logarithmic growth phase were divided into four groups. The non-targeted group and the single magnetic target group were added with PFH-Fe3O4@ADM nanoparticles(0.625mg/mL). The single folic acid target group and folic acid-magnetic dual target group were added with FA-PFH-Fe3O4@ADM nanoparticles(0.625mg/mL). A 4T magnet was placed at the side of the orifice plate of the single magnetic target group and the folic acid-magnetic double target group to evaluate the targeting ability of nanoparticles on Y79 cells. In addition, the ability of FA-PFH-Fe3O4@ADM nanoparticles ultrasound/photoacoustic/magnetic resonance three-mode imaging in vitro was observed.RESULT: FA-PFH-Fe3O4@ADM nanoparticles were successfully prepared with uniform distribution and uniform spherical structure. The average particle size of nanoparticles was 338.6±2.20 nm. ADM and Fe3O4 were successfully loaded, with an encapsulation efficiency of(41.76±4.12)% and(59.06±13.63)%, respectively. Nanoparticles had good paramagnetic properties and showed no obvious toxicity to Y79 cells. The phagocytic rate of the folic acid-magnetic dual target group(86.19±0.55)% was significantly higher than that of the single folate target group(43.36±5.91)% and single magnetic target group [(28.58±3.23)%, P

Purpose To investigate the mechanism through which hyperthermia promotes exosome secretion and drug sensitivity in adriamycin-resistant breast cancer. Materials and Methods We first evaluated the effect of hyperthermia on adriamycin-resistant breast cancer viability and used transmission electron microscopy, nanoparticle tracking analysis, and a bicinchoninic acid kit to validate the effect of hyperthermia on exosome secretion. The effective targeting molecules and pathways changed by hyperthermia were explored by RNA microarray and verified in vitro. The adriamycin-resistant MCF-7/ADR cells co-incubated with the exosomes produced by MCF-7/ADR cells after hyperthermia were assessed. The uptake of exosomes by MCF-7/ADR cells after hyperthermia treatment was evaluated by confocal microscopy. Finally, the mechanism through which hyperthermia promotes exosome secretion by hyperthermia was determined. Results Hyperthermia significantly suppressed the growth of adriamycin-resistant breast cancer cells and increased drug sensitivity by upregulating FOS and CREB5, genes related to longer overall survival in breast cancer patients. Moreover, hyperthermia promoted exosome secretion through Rab7b, a small GTPase that controls endosome transport. The upregulated FOS and CREB5 antioncogenes can be transferred to MCF-7/ADR cells by hyperthermia-treated MCF-7/ADR cell-secreted exosomes. Conclusions Our results demonstrated a novel function of hyperthermia in promoting exosome secretion in adriamycin-resistant breast cancer cells and revealed the effects of hyperthermia on tumor cell biology. These hyperthermia-triggered exosomes can carry antitumor genes to the residual tumor and tumor microenvironment, which may be more beneficial to the effects of hyperthermia. These results represent an exploration of the relationship between therapeutic strategies and exosome biology.

Abstract Background More initial clinical node‐positive breast cancer patients achieve axillary pathological complete response (ax‐pCR) after neoadjuvant systemic therapy (NST). Restaging axillary status and performing de‐escalated surgical procedures to replace routine axillary lymph nodes dissection (ALND) is urgently needed. Targeted axillary lymph node biopsy (TLNB) is a novel de‐escalated surgical strategy marking metastatic axillary nodes before NST and targeted dissection and biopsy intraoperatively to tailor individual axillary management. Methods This study provided a systematic review and meta‐analysis to evaluate the feasibility and diagnosis accuracy of TLNB. Prospective and retrospective clinical trials on TLNB were searched from Pubmed, Embase, and Cochrane. Identification rate (IFR), false‐negative rate (FNR), negative predictive value (NPV), and rate of ax‐pCR were the outcomes of this meta‐analysis. Results One thousand nine hundred and twenty patients attempted TLNB, with an overall IFR of 93.5% (95% confidence interval [CI] 90.1%–96.2%). IFR of three nodal marking methods, namely iodine seeds, clips, and carbon dye, was 95.6% (95% CI 91.2%–98.7%), 91.7% (95% CI 87.3%–95.4%), and 97.1% (95% CI 89.1%–100.0%), respectively. Of them, 847 patients received ALND, with an overall FNR of 5.5% (95% CI 3.3%–8.0%), and NPV ranged from 90.1% to 96.1%. Regression analysis showed that the overlap of targeted and sentinel biopsied nodes might associate with IFRs and FNRs. Conclusion TLNB is a novel, less invasive surgical approach to distinguish initial node‐positive breast cancer that achieves negative axillary conversion after NST. It yields an excellent IFR with a low FNR and a high NPV. A combination of preoperative imaging, intraoperative TLNB with SLNB, and postoperative nodal radiotherapy might affect the future treatment paradigm of primary breast cancer with nodal metastases.

Purpose: Venous thromboembolism (VTE) is a major health issue among hip fracture patients. This study aimed to develop an information platform based on a mobile application and then evaluate whether information platform-based nursing could improve patient's drug compliance and reduce the incidence of VTE in hip fracture patients. Methods: This study retrospectively analyzed hip fracture patients who were treated with conventional prevention and intervention methods for VTE (control group) between January 2008 and November 2012, and prospectively analyzed hip fracture patients who were treated with nursing intervention based on the information platform (study group) between January 2016 and September 2017. All the patients included in the both groups were hip fracture patients who had an age over 50 years, treated with surgery, and hospitalized ≥ 48 h. Patients were excluded if they admitted to hospital due to old fractures, had a severe bleeding after 72 h of admission, diagnosed with any type of VTE, or refused to participate in the study. The information platform was divided into medical, nursing, and patient interface. Based on the information platform, medical practitioners and nurses could perform risk assessments, monitoring management and early warnings, preventions and treatments, health educations, follow-up, and other aspects of nursing interventions for patients. This study compared essential characteristics, drug compliance, VTE occurrence, and mean length of hospitalization between the two groups. Besides, a subgroup analysis was performed in the study group according to different drug compliances. SPSS 18.0 software (IBM Corp., NY, and USA) was used for statistical analysis. Results: Altogether 1177 patients were included in the control group, and 491 patients in the study group. Regarding baseline data, patients in the study group had more morbidities than those in the control group (p