Defect compensation and intervalence charge transfer state-based Pr3+-doped niobate antithermal quenching phosphors.

Herein, a scheme of Sr2+/Ca2+ ion substitution was employed to simultaneously regulate the defect and intervalence charge transfer (IVCT) state of Sr2-xCaxNb2O7:Pr3+ phosphors, resulting in a dual-modulation strategy for enhancing phosphor thermal stability.

Nuclear Factor Erythroid 2-Related Factor 2 as a Potential Therapeutic Target in Neonatal Hypoxic-Ischemic Encephalopathy.

Hypoxic-ischemic encephalopathy (HIE) is a prominent cause of neonatal mortality and neurodevelopmental disorders; however, effective therapeutic interventions remain limited. During neonatal hypoxic-ischemic injury events, increased reactive oxygen species (ROS) production and decreased antioxidant levels lead to the induction of oxidative stress, which plays a pivotal role in the pathological process of neonatal HIE. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key endogenous antioxidant transcription factor that protects against oxidative stress by promoting the transcription of various antioxidant genes. It has been demonstrated that Nrf2 signaling pathway activation by different compounds may protect against neonatal HIE. This review outlines the role of oxidative stress in neonatal HIE and summarizes the impact of antioxidants on neonatal HIE via activation of the Nrf2 signaling pathway. In conclusion, Nrf2 signaling pathway potentially exerts antioxidant, anti-inflammatory, antiapoptotic and antiferroptotic effects, thereby emerging as a focal point for future neonatal HIE treatment strategies.

Oxygen concentration titration guided by oxygen reserve index during pediatric laryngeal surgery with high-flow nasal cannula oxygen: a randomized controlled trial.

PURPOSE: The objective of this study was to evaluate whether adjusting the oxygen concentration guided by the Oxygen Reserve Index (ORI) during pediatric laryngeal surgery with High Flow Nasal Cannula Oxygen (HFNO) could achieve postoperative PaO2 close to physiological levels while ensuring adequate oxygenation in surgery. METHODS: Sixty pediatric patients undergoing laryngeal surgery or examination were randomly assigned to two groups. The ORI group received oxygen concentration adjustments every 5 min to maintain a target ORI value of 0.21, whereas the control group did not undergo any adjustments. Postoperative PaO2, time weighted average fraction of inspired oxygen (FiO2), and mean Peripheral Oxygen Saturation (SpO2) were compared between groups. Finally, some analyses were conducted to examine the relationship of ORI with PaO2. RESULTS: In general, the postoperative PaO2 was 164.9 ± 48.8 mmHg in ORI group and 323.0 ± 87.7 mmHg in control group (P < 0.01). The time weighted average FiO2 in the ORI group was 85.9 [81.8-92.7] %. There was no significant difference in mean SpO2 between the two groups (ORI vs. control: 98.4 [97.7-99.2] vs. 98.8 [97.7-99.5]; P = 0.36). According to the analyses, the optimal cut value for ORI was determined to be 0.195 when PaO2 was 150 mmHg. CONCLUSIONS: In pediatric laryngeal surgery with HFNO, reducing oxygen concentration guided by ORI helped achieve postoperative PaO2 levels closer to physiological norms without compromising intra-operative oxygenation.

Cost-Effective and Scalable Solar Interface Evaporators Derived from Industry Waste for Efficient Solar Steam Generation.

Interfacial solar steam generation for sustainable and eco-friendly desalination and wastewater treatment has attracted much attention. However, costly raw materials and complex preparation processes pose constant challenges to its wide promotion. Herein, a novel, cost-effective, and scalable strategy is presented for preparing solar interface evaporators using industrial waste as a raw material. Modified polyethylene foam evaporators (M-EPEs) are simply prepared by drilling and then hydrophilic modification of industrial waste (EPE-1). M-EPEs not only retain the strong mechanical properties and thermal insulating properties (0.047 W·m-1·K-1) of EPE-1 but also exhibit superhydrophilicity and strong light absorption (over 90%). M-EPEs achieve a high evaporation rate of 1.497 kg·m-2·h-1 and photothermal efficiency of up to 93.8% under 1 kW·m-2 solar illumination. Moreover, it has excellent stability and salt tolerance. Our work addresses the environmental issues of recycling polyethylene waste and provides a facile and efficient strategy for designing low-cost, large-scale solar interface evaporators for desalination.

Construction of thermally stable Tb3+-activated green-emitting phosphors: dual driving strategy of doping concentration and excitation wavelength.

The realization of thermally stable Tb3+-doped green emission at high temperatures in solid-state lighting is still a crucial challenge. Nevertheless, the study on modulating the thermally stable luminescence at high temperatures is seldom reported. The position of the intervalence charge transfer (IVCT) energy level is used to systematically investigate the thermal quenching performance of Tb3+-activated green-emitting phosphors with varying concentration gradients of Gd1-xTaO4:xTb3+ (x = 0.1%, 0.5%, and 2%) in this study. The IVCT energy levels were determined according to the empirical formula to show a decreasing trend, consistent with the position of the IVCT energy levels measured in the excitation and diffuse reflectance spectra. Moreover, the thermal quenching performance of different wavelength excitation positions (host absorption, 4f-5d of Tb3+, and Tb3+-Ta5+ IVCT band) is quite different. The modulation of thermal quenching performance among distinct phosphors when subjected to host excitation or IVCT excitation can be elucidated through optimal positions within the energy levels associated with IVCT. The diverse concentration gradient samples exhibit varying degrees of thermal quenching performance in the variable-temperature spectra. The fluorescence lifetimes of the samples are generally comparable but slightly lower. The quantum efficiency rapidly improves as the Tb concentration increases. The underlying mechanism governing this phenomenon is elucidated by constructing a model that encapsulates the interplay between the compensating and quenching channels, in addition to the energy conversion of Tb3+ into Gd3+. The abovementioned results indicate that the dual driving scheme of the doping concentration and excitation wavelength is an effective means to regulate the thermal quenching performance of Tb-activated green-emitting tantalate phosphors.

Enhanced thermally stable performance of Pr3+-doped vanadate phosphor by inhibiting the intervalence charge transfer quenching channel.

Praseodymium (Pr3+) ion and the transition metal vanadium (V5+) ion with d0 electronic configuration can form an intervalence charge transfer (IVCT) band, which can function both as a compensatory channel for its red emission and as a quenching channel, thus affecting the luminescence thermal stability of the phosphors. Research studies reveal that the emission of Pr3+ in the YVO4 matrix can be quenched by the IVCT mechanism, thereby limiting the application of phosphors. As such, the present contribution is based on the solid solution replacement strategy to inhibit the constitutent of the IVCT quenching channel and thus improve thermal stability. Therefore, phosphonium (P5+) with a valence state matching V5+ and a similar ion radius was selected for the V/P substitution. It lacks a d0 electron configuration, preventing the formation of an IVCT band with Pr3+ and thereby inhibiting the construction of the quenching channels to enhance thermal stability. While the empirical formula of IVCT indicates a decrease in the IVCT energy level from 3.32438 to 3.06251 eV upon the introduction of P5+, the PLE spectra demonstrate a sharp reduction in IVCT intensity, i.e., weakening of the quenching channel. The thermal stability of the phosphors at different excitation locations was enhanced with the rise of P5+ concentration. When excited at the 3P2 level, the Y0.995PO4:0.5%Pr3+ phosphor demonstrated highly stable red emission from 303 to 523 K, with a luminescence integrated intensity ranging from 95.5% to 105.3% compared to that at 303 K. This research provides a novel approach for inhibiting the IVCT quenching channel and broadens the commercial value of YVO4:Pr3+ phosphor for various applications.

Airway management with Hi-flow nasal cannula oxygen in children with severe laryngeal obstruction.

BACKGROUND: The aim of this study was to report our initial experience in airway management in young children with severe laryngeal obstruction. Hi-flow nasal cannula oxygen (HFNO) with spontaneous respiration was used as a new airway management strategy in young children undergoing suspension laryngoscopic surgery. METHODS: Children aged between 1 day and 24 months scheduled for suspension laryngoscopy were retrospectively studied. The data collected included the patients' age, gender, American Society of Anaesthesiologists physical status classification, comorbidities, preoperative physiological status, methods of induction and maintenance of anesthesia, course of the disease and surgical options, lowest oxygen saturation recorded, transcutaneous CO2, duration of operation, and patients' need for rescue methods. RESULTS: A total of 38 patients successfully underwent suspension laryngoscopy under HFNO with spontaneous respiration. 19 patients were less than 1 year old (7 neonates), while the other half were less than or equal to 2 years old. The median [IQR (range)] lowest oxygen saturation recorded during the operation was 98 [93-99 (91-99)] %. The median [IQR (range)] duration of HFNO with spontaneous respiration was 65 [45-100 (30-200)] minutes. The median [IQR (range)] PCO2/PtcCO2 at the end of the spontaneous ventilation period was 54 [48-63 (39-70)] mmHg, which was the same as the preoperative PCO2 despite a long operation time. CONCLUSIONS: HFNO with spontaneous respiration emerged as a new airway management strategy in young children with severe laryngeal obstruction that was beneficial in maintaining oxygenation and was superior to transnasal humidified rapid insufflation ventilatory exchange (THRIVE) in terms of the rising rate of PCO2 in these patients, thereby prolonging the safety time of the operation.

Single-cell transcriptome analysis indicates fatty acid metabolism-mediated metastasis and immunosuppression in male breast cancer.

Male breast cancer (MBC) is a rare but aggressive malignancy with cellular and immunological characteristics that remain unclear. Here, we perform transcriptomic analysis for 111,038 single cells from tumor tissues of six MBC and thirteen female breast cancer (FBC) patients. We find that that MBC has significantly lower infiltration of T cells relative to FBC. Metastasis-related programs are more active in cancer cells from MBC. The activated fatty acid metabolism involved with FASN is related to cancer cell metastasis and low immune infiltration of MBC. T cells in MBC show activation of p38 MAPK and lipid oxidation pathways, indicating a dysfunctional state. In contrast, T cells in FBC exhibit higher expression of cytotoxic markers and immune activation pathways mediated by immune-modulatory cytokines. Moreover, we identify the inhibitory interactions between cancer cells and T cells in MBC. Our study provides important information for understanding the tumor immunology and metabolism of MBC.

To Assess the Role of Immune Infiltrating Immune Cells of Patients With Chronic Heart Failure With Atrial Fibrillation and Nursing Care in These Patients.

This research aimed to assess the role of immune infiltrating immune cells of patients with chronic heart failure with atrial fibrillation and nursing care in these patients. For this aim, 400 patients from 22 centres across our nations were recruited in the index cohort based on worsening signs/symptoms and poor management of HF. The validation cohort consisted of patients who had previously participated in the index cohort. The primary goal was to reduce all-cause mortality as well as unscheduled hospitalisations due to heart failure. Hospitalizations for heart failure (HF), total mortality, and death attributable to cardiovascular disease were secondary objectives. Results showed that interleukin-6 (IL-6) levels in patients ranged from 3.1 to 11.21 pg/mL on average, with 228 patients (or 57% of the total) having IL-6 levels that were higher than the 95th percentile of normal values (> 4.45 pg/mL). The average age of the group was 69.85±9.68 years, and there were 295 males in the group (73.75 percent). 17 Patients who had higher levels of IL-6 tended to be older, more frequently suffered from heart failure with preserved ejection fraction (HFpEF), and more frequently suffered from anaemia, diabetes, and atrial fibrillation. Patients who had higher levels of IL-6 also had a greater likelihood of suffering from these conditions. Patients who had higher levels of IL-6 also had a shorter distance travelled during the 6MWT and had a lower chance of completing the test. Both test completion [OR (95% CI) per doubling of IL-6: 0.81 (0.71 - 0.91), P< 0.001] and total distance covered [B (95% CI) per doubling of IL-6: 28.11 (32.58 to-21.98), P< 0.001] were negatively associated with increasing levels of IL-6, Patients who had high levels of IL-6 had higher median hepcidin levels than patients who had low levels of IL-6. This was discovered by comparing the two groups' hepcidin levels. There was a correlation between increased levels of IL-6 and increased levels of NT-proBNP and CRP, as well as a reduction in eGFR. In conclusion, independent predictors of IL-6 were younger age, high-flow partial ejection fraction (HFpEF), atrial fibrillation (AF), iron insufficiency, and higher levels of NT-proBNP, PCT, hepcidin, and TNF-/IL-1 related biomarkers. Last but not least, IL-6 levels in the plasma were able to predict death and/or hospitalisation due to HF on their own, although they did not contribute to differentiation in prior models.

Diagnosing sentinel lymph node metastasis of T1/T2 breast cancer with conventional ultrasound combined with double contrast-enhanced ultrasound: a preliminary study.

Background: In patients with T1/T2 breast cancer (BC), sentinel lymph node (SLN) status is essential for prognosis and treatment. This study investigated the value of conventional ultrasound combined with double contrast-enhanced ultrasound in diagnosing the metastasis of SLNs in patients with T1/T2 BC. Methods: This study employed a prospective design (this diagnostic study was not registered on a clinical trial platform), and the participants formed a convenience series. Based on the inclusion and exclusion criteria, 163 patients with BC who received treatment in the First Affiliated Hospital of Soochow University from July 2017 to December 2021 were included in this study. A total of 165 SLNs from 163 patients with T1/T2 BC were analyzed. All patients underwent percutaneous contrast-enhanced ultrasound (PCEUS) to trace SLNs before the operation. Subsequently, all patients underwent conventional ultrasound and intravenous contrast-enhanced ultrasound (ICEUS) examinations to observe the SLNs. The results of the conventional ultrasound, ICEUS, and PCEUS of the SLNs were analyzed. The associations between the risk of SLN metastasis and imaging features were evaluated via a nomogram based on the pathological results. Results: Overall, 54 metastatic SLNs and 111 nonmetastatic SLNs were evaluated. Metastatic SLNs displayed a greater cortical thickness, area ratio, eccentric fatty hilum, and hybrid blood flow on conventional ultrasound compared with nonmetastatic SLNs (P<0.001). According to PCEUS, 75.93% of metastatic SLNs showed heterogeneous enhancement (type II and III), and 73.88% of nonmetastatic SLNs showed homogeneous enhancement (type I; P<0.001). According to ICEUS, heterogeneous enhancement (type B/C, 20.37% vs. 11.71%) and overall enhancement (55.56% vs. 23.42%) were more common in metastatic SLNs than in nonmetastatic SLNs (P<0.001). Logistic regression analysis showed that the cortical thickness and enhancement type of PCEUS were independent predictors of SLN metastasis. Moreover, a nomogram combining these factors showed a high diagnostic ability for SLN metastasis (unadjusted concordance index 0.860, 95% CI: 0.730-0.990; bootstrap-corrected concordance index 0.853). Conclusions: The nomogram of cortical thickness and enhancement type of PCEUS could effectively diagnose SLN metastasis in patients with T1/T2 BC.

Comparison of the application of high-flow nasal oxygen with two different oxygen concentrations in infant and child laryngotracheal surgery.

Background: This study aimed to compare the use of the STRIVE Hi technique with 70 and 100% oxygen concentrations in children with 1st or 2nd degree laryngeal obstruction undergoing suspension laryngoscopic surgery. Methods: Children aged 1 month to 6 years scheduled for suspension laryngoscopic surgery with spontaneous respiration were randomly divided into the 70% oxygen concentration group (HFNO70% group) and the 100% oxygen concentration group (HFNO100% group). The data recorded for all the patients included age and sex, comorbidities, preoperative physiological status, methods of induction and maintenance of anesthesia, course of the disease and surgical options, and duration of operation. The primary endpoint was the lowest oxygen saturations during the surgery. The secondary endpoints included the partial pressure of oxygen PaO2, the arterial pressure of carbon dioxide PaCO2, the peak transcutaneous carbon dioxide PtcCO2, and the incidence of desaturation (defined as SpO2 < 90%) or hypercarbia (PtcCO2 > 65 mmHg). Results: A total of 80 children with 1st or 2nd degree laryngeal obstruction were included in the analysis. The median [IQR (range)] duration of spontaneous ventilation using STRIVE Hi was 52.5 [40-60 (30-170)]min and 62.5 [45-81 (20-200)]min in the HFNO 70% and HFNO 100% groups, respectively (p = 0.99); the lowest oxygen saturation recorded during the operation was 97.8 ± 2.1% and 96.8 ± 2.5%, respectively (p = 0.053); the mean PaO2 at the end of surgery was 184.6 ± 56.3 mmHg and 315.2 ± 101.3 mmHg, respectively (p < 0.001); and the peak transcutaneous CO2 was 58.0 ± 13.0 mmHg and 60.4 ± 10.9 mmHg, respectively (p = 0.373), despite a long operation time. Conclusion: STRIVE Hi had a positive effect on children undergoing tubeless laryngeal surgery with spontaneous ventilation, and for children with 1st or 2nd degree laryngeal obstruction, there was no significant difference in maintaining the intraoperative oxygenation between the 70 and 100% oxygen concentration groups. The 100% oxygen concentration group showed significant hyperoxia, which has been proven to be associated with multiple organ damage. Using a relatively lower oxygen concentration of 70% can effectively reduce the hazards associated with hyperoxia compared to 100% oxygen concentration. Clinical trial registration: [www.chictr.org.cn], identifier [CHICTR2200064500].

Echinocystic acid alleviated hypoxic-ischemic brain damage in neonatal mice by activating the PI3K/Akt/Nrf2 signaling pathway.

Neonatal hypoxic-ischemic encephalopathy (HIE) is considered a major cause of death and long-term neurological injury in newborns. Studies have demonstrated that oxidative stress and apoptosis play a major role in the progression of neonatal HIE. Echinocystic acid (EA), a natural plant extract, shows great antioxidant and antiapoptotic activities in various diseases. However, it has not yet been reported whether EA exerts a neuroprotective effect against neonatal HIE. Therefore, this study was undertaken to explore the neuroprotective effects and potential mechanisms of EA in neonatal HIE using in vivo and in vitro experiments. In the in vivo study, a hypoxic-ischemic brain damage (HIBD) model was established in neonatal mice, and EA was administered immediately after HIBD. Cerebral infarction, brain atrophy and long-term neurobehavioral deficits were measured. Hematoxylin and eosin (H&E), terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and dihydroethidium (DHE) staining were performed, and the contents of malondialdehyde (MDA) and glutathione (GSH) were detected. In the in vitro study, an oxygen-glucose deprivation/reperfusion (OGD/R) model was employed in primary cortical neurons, and EA was introduced during OGD/R. Cell death and cellular ROS levels were determined. To illustrate the mechanism, the PI3K inhibitor LY294002 and Nrf2 inhibitor ML385 were used. The protein expression levels of p-PI3K, PI3K, p-Akt, Akt, Nrf2, NQO1, and HO-1 were measured by western blotting. The results showed that EA treatment significantly reduced cerebral infarction, attenuated neuronal injury, and improved brain atrophy and long-term neurobehavioral deficits in neonatal mice subjected to HIBD. Meanwhile, EA effectively increased the survival rate in neurons exposed to OGD/R and inhibited oxidative stress and apoptosis in both in vivo and in vitro studies. Moreover, EA activated the PI3K/Akt/Nrf2 pathway in neonatal mice following HIBD and in neurons after OGD/R. In conclusion, these results suggested that EA alleviated HIBD by ameliorating oxidative stress and apoptosis via activation of the PI3K/Akt/Nrf2 signaling pathway.

Expression and Prognostic Value of PIK3CA, VEGF, IL-8, IL-10, and RIP2 in Diffuse Large B-Cell Lymphoma.

Background: To explore clinical features and prognostic value of vascular endothelial growth factor (VEGF), interleukin (IL) 8, IL-10, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), and receptor-interacting protein-2 (RIP2) in diffuse large B-cell lymphoma (DLBCL). Methods: A total of 68 DLBCL patients admitted to the Affiliated Hospital of Hebei Engineering University from January 2017 to June 2021 were included in this retrospective analysis. Serum VEGF was detected by enzyme-linked immunosorbent assay, serum IL-8 and IL-10 were detected by chemiluminescent enzyme immunoassay, and expression of PIK3CA and RIP2 in tumors was detected by immunohistochemistry. The correlation between clinical features of DLBCL and tumor-related index were analyzed. Cox regression was conducted to explore risk factors and hazard ratio. Results: The serum level or expressions of VEGF, IL-8, IL-10, and RIP2 were significantly elevated with the increase of Ann Arbor Stage, International Prognostic Index (IPI) scores, Eastern Cooperative Oncology Group (ECOG) scores, serum lactate dehydrogenase (LDH) level, and the number of extranodal sites (all P < 0.05). Beside, these serum indexes were significantly higher in patients with the presence of extranodal involvement and germinal center B-cell (GCB), but significantly lower in patients with the presence of bone marrow involvement (all P < 0.05). Cox regression analysis for overall survival revealed that high expression of VEGF, high level of serum IL-8, serum IL-10, and RIP2, Ann Arbor Stage (III-IV), number of extranodal sites (>1), serum LDH level (≥245 U/L), IPI scores (3-5), ECOG scores (≥2), and bone marrow involvement were independent risk factors for the prognosis of DLBCL patients (all P < 0.05). Conclusion: The serum levels of VEGF, IL-8, and IL-10, as well as the expression of RIP2 and PIK3CA in tumor tissues, were highly correlated to clinical features of DLBCL, and high expression level of these indexes may have adverse effects for the prognosis of DLBCL patients.

Genome-wide identification, molecular evolution and expression analysis of the non-specific lipid transfer protein (nsLTP) family in Setaria italica.

BACKGROUND: Foxtail millet (Setaria italica L.) is a millet species with high tolerance to stressful environments. Plant non-specific lipid transfer proteins (nsLTPs) are a kind of small, basic proteins involved in many biological processes. So far, the genome of S. italica has been fully sequenced, and a comprehensive understanding of the evolution and expression of the nsLTP family is still lacking in foxtail millet. RESULTS: Forty-five nsLTP genes were identified in S. italica and clustered into 5 subfamilies except three single genes (SinsLTP38, SinsLTP7, and SinsLTP44). The proportion of SinsLTPs was different in each subfamily, and members within the same subgroup shared conserved exon-intron structures. Besides, 5 SinsLTP duplication events were investigated. Both tandem and segmental duplication contributed to nsLTP expansion in S. italica, and the duplicated SinsLTPs had mainly undergone purifying selection pressure, which suggested that the function of the duplicated SinsLTPs might not diverge much. Moreover, we identified the nsLTP members in 5 other monocots, and 41, 13, 10, 4, and 1 orthologous gene pairs were identified between S. italica and S. viridis, S. bicolor, Z. mays, O. sativa, and B. distachyon, respectively. The functional divergence within the nsLTP orthologous genes might be limited. In addition, the tissue-specific expression patterns of the SinsLTPs were investigated, and the expression profiles of the SinsLTPs in response to abiotic stress were analyzed, all the 10 selected SinsLTPs were responsive to drought, salt, and cold stress. Among the selected SinsLTPs, 2 paired duplicated genes shared almost equivalent expression profiles, suggesting that these duplicated genes might retain some essential functions during subsequent evolution. CONCLUSIONS: The present study provided the first systematic analysis for the phylogenetic classification, conserved domain and gene structure, expansion pattern, and expression profile of the nsLTP family in S. italica. These findings could pave a way for further comparative genomic and evolution analysis of nsLTP family in foxtail millet and related monocots, and lay the foundation for the functional analysis of the nsLTPs in S. italica.

Photonic passbands induced by optical fractal effect in Cantor dielectric multilayers.

We investigate the splitting and incorporation of optical fractal states in one-dimensional photonic quasi-crystals. The aperiodic crystals which are composed of two different dielectrics submit to Cantor sequence. Defects in Cantor crystals can greatly enhance the localization of electric field, which induces the optical fractal effect. The number of optical fractal states increases exponentially with the generation number of Cantor sequence. Moreover, the optical fractal characteristics depend on the incident angle of light, of which the fractal states may split/incorporate by modulating the value of incident angle. This study could be utilized for band-pass filters and reflectors.

Long noncoding RNA plasmacytoma variant translocation 1 promotes progression of colorectal cancer by sponging microRNA-152-3p and regulating E2F3/MAPK8 signaling.

The purpose of this study was to investigate the pathogenesis of colorectal cancer (CRC) and the effects of the long noncoding RNA plasmacytoma variant translocation 1 (PVT1) on CRC progression. Bioinformatics analysis verified PVT1 expression in tumor and normal tissues. Quantitative PCR and western blotting were used to measure mRNA and protein levels, respectively. The MTT, Transwell, colony formation, and in vivo assays were used to assess the effects of PVT1 on proliferation, migration, and invasion by CRC cells. Both PVT1 and microRNA (miR)-152-3p were shown to be colocalized in CRC cells using FISH assay. The target genes of miR-152-3p were predicted and verified by bioinformatics analysis, luciferase assay, and RNA pull-down assay. The ChIP assay revealed that E2F3 binds with the promoter of MAPK8. We found that PVT1 was overexpressed in CRC specimens, and its expression was higher in CRC cells than normal intestinal cells. Overexpression of PVT1 enhanced the proliferation, migration, and invasion of CRC cells, whereas PVT1 knockdown inhibited these processes. MicroRNA-152-3p was a target of PVT1, and E2F3 was a target of miR-152-3p. Rescue experiments confirmed the interaction between miR-152-3p and PVT1 and between miR-152-3p and E2F3. Luciferase and ChIP assay results confirmed that E2F3 modulates the transcriptional activation of MAPK8. Long noncoding RNA PVT1 activated E2F3 signaling by sponging miR-152-3p. The PVT1/miR-152-3p/E2F3/MAPK8 axis promoted CRC progression.

Profiling Receptor Tyrosine Kinase Fusions in Chinese Breast Cancers.

BACKGROUND: Receptor tyrosine kinases (RTKs) are a class of tyrosine kinases that regulate cell-to-cell communication and control a variety of complex biological functions. Dysregulation of RTK signaling partly due to chromosomal rearrangements leads to novel tyrosine kinase fusion oncoproteins that are possibly driver alterations to cancers. Targeting some RTK fusions with specific tyrosine kinases inhibitors (TKIs) is an effective therapeutic strategy across a spectrum of RTK fusion-related cancers. However, there is still a paucity of extensive RTK fusion investigations in breast cancer. This study aims to characterize RTK fusions in Chinese breast cancer patients. METHODS: An in-house DNA sequencing database of 1440 Chinese breast cancer patients with a capture-based panel (520 gene or 108 gene-panel) was thoroughly reviewed. A total of 2,229 samples including 1,045 tissues and 1,184 plasmas were analyzed. RTK fusion was defined as an in-frame fusion with the tyrosine kinase domain of the RTK completely retained. Concomitant mutations were also analyzed and tumor mutational burden (TMB) was calculated. Patients' clinical characteristics were retrieved from case records. RESULTS: A total of 30 RTK fusion events were identified from 27 breast cancer patients with a prevalence of 1.875%%. FGFR2 fusions were seen the most commonly (n=7), followed by RET (n=5), ROS1 (n=3), NTRK3 (n=3), BRAF (n=2), and NTRK1 (n=2). Other RTK fusions including ALK, EGFR, FGFR1, FGFR3, MET, and NTRK2 were identified in one patient each. A total of 27 unique resultant fusion proteins (22 with a novel partner) were discovered including 19 intrachromosomal rearrangements and 8 interchromosomal ones. Twenty-one fusions had the tyrosine kinase domain in-frame fused with a partner gene and six were juxtaposed with an intergenic space. Among the 27 fusions, FGFR2-WDR11 (E17: intergenic) (n=3) and ETV6-NTRK3 (E5:E15) (n=2) occurred recurrently. Of note, the normalized abundance of RTK fusion (fusion AF/max AF) correlated negatively with TMB (r=-0.48, P=0.017). Patients with TMB < 8 (Mutations/Mb) displayed a higher fusion abundance than those with TMB ≥ 8 (Mutations/Mb) (P=0.025). Moreover, CREBBP mutation only co-occurred with FGFR2 fusion (P=0.012), while NTRK3 fusion and TP53 mutation were mutually exclusive (P=0.019). CONCLUSION: This is the first study comprehensively delineating the prevalence and spectrum of RTK fusions in Chinese breast cancers. Further study is ongoing to identify the enriched subpopulation who may benefit from RTK fusion inhibitors.

Platinum-Based Chemotherapy and Immunotherapy in Early Triple-Negative Breast Cancer: A Meta-Analysis and Indirect Treatment Comparison.

BACKGROUND: Triple-negative breast cancer (TNBC) comprises 15% of invasive breast cancers. Platinum-based chemotherapy and immune checkpoint inhibitors (ICIs) have been extensively researched in recent years as promising treatments in the neoadjuvant setting. However, clinical data is lacking in direct comparisons of these two treating regimens. METHODS: We conducted an online search on PubMed, Embase, Cochrane Online Library and key oncological meetings for available randomized controlled trials (RCTs) investigating ICIs or platinum drugs versus anthracyclines and taxane-based neoadjuvant chemotherapy (AT-based NACT). Conventional meta-analyses were conducted separately, and then indirect comparisons for clinical efficacy and safety profile were performed between ICIs and platinum drugs using AT-based NACT as a common comparator. RESULTS: Seven random controlled trials (RCTs) with 1,647 patients were included in the meta-analysis. The indirect comparison demonstrated that ICIs plus chemotherapy significantly improved pathological complete response (pCR) rate (p = 0.00445, OR, 1.78; 95%CI, 0.70-4.53), and decreased the adverse effect (AE) related discontinuance versus platinum-based chemotherapy (P = 0.00015; OR 0.46; 95%CI, 0.26-0.82). CONCLUSION: ICIs plus chemotherapy showed increased pCR rate and decreased adverse effects compared with platinum-based chemotherapy in early TNBC. However, subgroup analysis and survival data to explore the proper patients for each treatment remains scarce. Therefore, further studies with powered direct comparisons of these two treating regimens are required.

Pseudogene legumain promotes thyroid carcinoma progression via the microRNA-495/autophagy pathway.

The pseudogene legumain (LGMN) has been reported to regulate cancer cell biology. However, the role of LGMN in thyroid carcinoma remains unknown. Herein, Cell Counting Kit 8 and Transwell assays were performed to evaluate cellular proliferation and invasion capacity, respectively. In addition, a tube formation assay was performed to assess HUVEC angiogenesis. The results showed that LGMN depletion attenuated cellular proliferation, invasion and tube formation ability, and that LGMN expression was dysregulated in thyroid carcinoma tumors. Furthermore, patients with high LGMN expression levels exhibited a lower overall survival rate than those with low expression levels. LGMN and microRNA (miR)-495 modulated the expression levels of autophagy-related gene 3 (ATG3) and p62. Finally, ATG3 overexpression rescued the LGMN-regulated thyroid carcinoma phenotype. In conclusion, LGMN was found to promote thyroid carcinoma progression via the miR-495/autophagy axis, thus providing novel insights for understanding the pathogenesis of thyroid carcinoma.

Correlation between sonographic features and pathological findings of cervical lymph node metastasis of differentiated thyroid carcinoma.

BACKGROUND: The aim of this study is to evaluate the relationship between the sonographic features and pathological findings of cervical lymph node metastasis of differentiated thyroid carcinoma (DTC). METHODS: A total of 49 patients who had thyroid surgery and lateral or central cervical lymph node dissection from October to December 2019 in our hospital were selected. All the lymph nodes included in the dissection were examined by intraoperative ultrasound and were divided into 5 groups according to the sonographic characteristics (A: overall hyperechoic group; B: hypoechoic with punctate hyperechoic group; C: mass hyperechoic group; D: cystic degeneration group; E: hypoechoic group without punctate hyperecho). All samples were sent to the Pathology Department according to the area of origin and classified and numbered for comparative analysis of the microscopic pathology and the sonogram. RESULTS: A total of 120 suspicious metastatic lymph nodes were finally screened out by intraoperative ultrasound. The sonographic signs of these suspicious metastatic lymph nodes in the lateral and central regions of the neck were significantly different from the normal lymph nodes. Besides, the indicators including sensitivity, specificity, accuracy, positive predictive value and negative predictive value of intraoperative ultrasound for detecting lateral and central lymph nodes were 89.04% vs. 82.98%, 93.83% vs. 80.00%, 90.97% vs. 81.10%, 92.86% vs. 70.91%, and 90.48% vs. 88.89%, respectively. The pathological features of metastatic lymph nodes were shown as follows: group A, diffuse distribution of follicular structure; group C, focal distribution of follicular structure; group B and E, atypical follicular epithelial cells with or without papillary structure. Necrosis and liquefaction were observed in group D. CONCLUSIONS: The relationship between sonographic features and follicular structure of metastatic lymph nodes are firmly related. A correct understanding of these features is practical to improve the diagnostic rate of conventional ultrasonography and reduce the incidences of misdiagnosis.