The prognostic significance of ubiquitination-related genes in multiple myeloma by bioinformatics analysis.

BACKGROUND: Immunoregulatory drugs regulate the ubiquitin-proteasome system, which is the main treatment for multiple myeloma (MM) at present. In this study, bioinformatics analysis was used to construct the risk model and evaluate the prognostic value of ubiquitination-related genes in MM. METHODS AND RESULTS: The data on ubiquitination-related genes and MM samples were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The consistent cluster analysis and ESTIMATE algorithm were used to create distinct clusters. The MM prognostic risk model was constructed through single-factor and multiple-factor analysis. The ROC curve was plotted to compare the survival difference between high- and low-risk groups. The nomogram was used to validate the predictive capability of the risk model. A total of 87 ubiquitination-related genes were obtained, with 47 genes showing high expression in the MM group. According to the consistent cluster analysis, 4 clusters were determined. The immune infiltration, survival, and prognosis differed significantly among the 4 clusters. The tumor purity was higher in clusters 1 and 3 than in clusters 2 and 4, while the immune score and stromal score were lower in clusters 1 and 3. The proportion of B cells memory, plasma cells, and T cells CD4 naïve was the lowest in cluster 4. The model genes KLHL24, HERC6, USP3, TNIP1, and CISH were highly expressed in the high-risk group. AICAr and BMS.754,807 exhibited higher drug sensitivity in the low-risk group, whereas Bleomycin showed higher drug sensitivity in the high-risk group. The nomogram of the risk model demonstrated good efficacy in predicting the survival of MM patients using TCGA and GEO datasets. CONCLUSIONS: The risk model constructed by ubiquitination-related genes can be effectively used to predict the prognosis of MM patients. KLHL24, HERC6, USP3, TNIP1, and CISH genes in MM warrant further investigation as therapeutic targets and to combat drug resistance.

Br, O-Modified Cu(111) Interface Promotes CO2 Reduction to Multicarbon Products.

Electrochemical reduction of CO2 to multicarbon (C2+) products with added value represents a promising strategy for achieving a carbon-neutral economy. Precise manipulation of the catalytic interface is imperative to control the catalytic selectivity, particularly toward C2+ products. In this study, a unique Cu/UIO-Br interface is designed, wherein the Cu(111) plane is co-modified simultaneously by Br and O from UIO-66-Br support. Such Cu/UIO-Br catalytic interface demonstrates a superior Faradaic efficiency of ≈53% for C2+ products (ethanol/ethylene) and the C2+ partial current density reached 24.3 mA cm-2 in an H-cell electrolyzer. The kinetic isotopic effect test, in situ attenuated total reflection Fourier transform infrared spectroscopy and density functional theory calculations have been conducted to elucidate the catalytic mechanism. The Br, O co-modification on the Cu(111) interface enhanced the adsorption of CO2 species. The hydrogen-bond effect from the doped Br atom regulated the kinetic processes of *H species in CO2RR and promoted the formation of *COH intermediate. The formed *COH facilitates the *CO-*COH coupling and promotes the C2+ selectivity finally. This comprehensive investigation not only provides an in-depth study and understanding of the catalytic process but also offers a promising strategy for designing efficient Cu-based catalysts with exceptional C2+ products.

Comparative efficacy and safety of CDK4/6 inhibitors combined with endocrine therapies for HR+/HER2-breast cancer: Systematic review and network meta-analysis.

Background: In recent years, the combination of targeted drugs, such as Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors, with endocrine therapy (ET), has emerged as a new research focus in the treatment of hormone receptor-positive (HR+) human epidermal growth factor receptor 2 negative (HER2-) breast cancer. This network meta-analysis aimed to systematically evaluate the efficacy and safety of CDK4/6 inhibitors combined with ET for HR+/HER2-breast cancer. Methods: A systematic search was conducted across PubMed, Web of Science, Cochrane Library, and GeenMedical databases to identify randomized controlled trials investigating the use of CDK4/6 inhibitors in combination with endocrine therapy for the treatment of HR+/HER2-breast cancer. The search period spanned from the inception of each database up to February 29, 2024. Data analysis was conducted using Stata 14.0 and R 4.1.0 software. Results: A total of 20 randomized controlled trials (RCTs) were included in this study, investigating the effectiveness of four CDK4/6 inhibitors-Abemaciclib, Dalpiciclib, Ribociclib, and Palbociclib-when combined with ET for the treatment of HR+/HER2-breast cancer. The results indicated that Abemaciclib + ET, Dalpiciclib + ET, Palbociclib + ET, and Ribociclib + ET exhibited similar therapeutic effects in terms of improving objective response rate (ORR), disease control rate (DCR) and reducing the occurrence of fatigue, all of which were superior to ET alone. However, in terms of prolonging progression-free survival (PFS) and overall survival (OS), Dalpiciclib + ET significantly improved PFS compared to Ribociclib + ET, Palbociclib + ET, Abemaciclib and Palbociclib. Ribociclib + ET significantly improved OS compared to Palbociclib + ET. Regarding overall adverse reaction events (AREs), Dalpiciclib + ET had a higher incidence compared to Ribociclib + ET. The incidence of neutropenia caused by Dalpiciclib + ET was significantly higher compared to Palbociclib + ET, Ribociclib + ET, Abemaciclib, and Palbociclib. Abemaciclib + ET demonstrated the worst safety profile concerning diarrhea. Conclusion: Abemaciclib + ET likely represents the most effective option in terms of therapeutic effects, but it is prone to causing diarrhea and fatigue. On the other hand, Dalpiciclib + ET likely demonstrates the best efficacy in terms of PFS but exhibits the poorest safety profile, particularly in relation to neutropenia. Therefore, clinicians should exercise increased vigilance in monitoring and managing adverse effects when prescribing Abemaciclib + ET and Dalpiciclib + ET.

Record-High T_{c} and Dome-Shaped Superconductivity in a Medium-Entropy Alloy TaNbHfZr under Pressure up to 160 GPa.

Superconductivity has been one of the focal points in medium and high-entropy alloys (MEAs-HEAs) since the discovery of the body-centered cubic (bcc) HEA superconductor in 2014. Until now, the superconducting transition temperature (T_{c}) of most MEA and HEA superconductors has not exceeded 10 K. Here, we report a TaNbHfZr bulk MEA superconductor crystallized in the BCC structure with a T_{c} of 15.3 K which set a new record. During compression, T_{c} follows a dome-shaped curve. It reaches a broad maximum of roughly 15 K at around 70 GPa before decreasing to 9.3 K at 157.2 GPa. First-principles calculations attribute the dome-shaped curve to two competing effects, that is, the enhancement of the logarithmically averaged characteristic phonon frequency ω_{log} and the simultaneous suppression of the electron-phonon coupling constant λ. Thus, TaNbHfZr MEA may have a promising future for studying the underlying quantum physics, as well as developing new applications under extreme conditions.

The efficacy and safety of short-term and low-dose IL-2 combined with tocilizumab to treat rheumatoid arthritis.

Background: Immunotherapy targeting factors related to immune imbalance has been widely employed for RA treatment. This study aimed to evaluate the efficacy and safety of low-dose interleukin (IL)-2 combined with tocilizumab (TCZ), a biologics targeting IL-6, in RA patients. Methods: Fifty adults with active RA who met the criteria with complete clinical data were recruited, and divided into three groups: control group (n=15), IL-2 group (n=26), and IL-2+TCZ group (n=9). In addition to basic treatment, participants in the IL-2 group received IL-2 (0.5 MIU/day), while participants in the IL-2+TCZ group received IL-2 (0.5 MIU/day) along with one dose of TCZ (8 mg/kg, maximum dose: 800 mg). All subjects underwent condition assessment, laboratory indicators and safety indicators detection, and records before treatment and one week after treatment. Results: Compared with the baseline, all three groups showed significant improvement in disease conditions, as evidenced by significantly reduced disease activity indicators. The low-dose IL-2 and combination treatment groups demonstrated a violent proliferation of Tregs, while the absolute number of Th1, Th2, and Th17 cells in the latter group showed a decreasing trend. The decrease in the Th17/Treg ratio was more pronounced in the IL-2+TCZ groups. No significant adverse reactions were observed in any of the patients. Conclusion: Exogenous low doses of IL-2 combined TCZ were found to be safe and effective in reducing effector T cells and appropriately increasing Treg levels in RA patients with high effector T cell levels. This approach helps regulate immune homeostasis and contributes to the prevention of disease deterioration. Clinical trial registration: https://www.chictr.org.cn/showprojEN.html?proj=13909, identifier ChiCTR-INR-16009546.

Population genetic structure of Pomacea canaliculata in China based on the COI and ITS1 genes.

Comprehending the phylogeography of invasive organisms enhances our insight into their distribution dynamics, which is instrumental for the development of effective prevention and management strategies. In China, Pomacea canaliculata and Pomacea maculata are the two most widespread and damaging species of the non-native Pomacea spp.. Given this species' rapid spread throughout country, it is urgent to investigate the genetic diversity and structure of its different geographic populations, a task undertaken in the current study using the COI and ITS1 mitochondrial and ribosomal DNA genes, respectively. The result of this study, based on a nationwide systematic survey, a collection of Pomacea spp., and the identification of cryptic species, showed that there is a degree of genetic diversity and differentiation in P. canaliculata, and that all of its variations are mainly due to differences between individuals within different geographical populations. Indeed, this species contains multiple haplotypes, but none of them form a systematic geographical population structure. Furthermore, the COI gene exhibits higher genetic diversity than the ITS1 gene. Our study further clarifies the invasive pathways and dispersal patterns of P. canaliculata in China to provide a theoretical basis.

Celastrol mediates CAV1 to attenuate pro-tumorigenic effects of senescent cells.

BACKGROUND: Cellular senescence is an emerging hallmark of cancers, primarily fuels cancer progression by expressing senescence-associated secretory phenotype (SASP). Caveolin-1 (CAV1) is a key mediator of cell senescence. Previous studies from our group have evidenced that the expression of CAV1 is downregulated by Celastrol (CeT). PURPOSE: To investigate the impact of CeT on cellular senescence and its subsequent influence on post-senescence-driven invasion, migration, and stemness of clear cell renal cell carcinoma (ccRCC). STUDY DESIGN AND METHODS: The expression levels of CAV1, canonical senescence markers, and markers associated with epithelial-mesenchymal transition (EMT) and stemness in clinical samples were assessed through Pearson correlation analysis. Senescent cell models were induced using DOX, and their impact on migration, invasion, and stemness was evaluated. The effects of CeT treatment on senescent cells and their pro-tumorigenic effects were examined. Subsequently, the underlying mechanism of CeT were explored using lentivirus transfection and CRISPR/Cas9 technology to silence CAV1. RESULTS: In human ccRCC clinical samples, the expression of the canonical senescence markers p53, p21, and p16 are associated with ccRCC progression. Senescent cells facilitated migration, invasion, and enhanced stemness in both ccRCC cells and ccRCC tumor-bearing mice. As expected, CeT treatment reduced senescence markers (p16, p53, p21, SA-ß-gal) and SASP factors (IL6, IL8, CXCL12), alleviating cell cycle arrest. However, it did not restore the proliferation of senescent cells. Additionally, CeT suppressed senescence-driven migration, invasion, and stemness. Further investigations into the underlying mechanism demonstrated that CAV1 is a critical mediator of cell senescence and represents a potential target for CeT to attenuate cellular senescence. CONCLUSIONS: This study presents a pioneering investigation into the intricate interplay between cellular senescence and ccRCC progression. We unveil a novel mechanism of CeT to mitigate cellular senescence by downregulating CAV1, thereby inhibiting the migration, invasion and stemness of ccRCC driven by senescent cells. These findings provide valuable insights into the underlying mechanisms of CeT and its potential as a targeted therapeutic approach for alleviating the aggressive phenotypes associated with senescent cells in ccRCC.

Age and mean platelet volume-based nomogram for predicting the therapeutic efficacy of metoprolol in Chinese pediatric patients with vasovagal syncope.

BACKGROUND: Vasovagal syncope (VVS) is the most common type of orthostatic intolerance in children. We investigated whether platelet-related factors related to treatment efficacy in children suffering from VVS treated with metoprolol. METHODS: Metoprolol-treated VVS patients were recruited. The median duration of therapy was three months. Patients were followed and divided into two groups, treament-effective group and treatment-ineffective group. Logistic and least absolute shrinkage selection operator regressions were used to examine treatment outcome variables. Receiver-operating characteristic (ROC) curves, precision-recall (PR) curves, calibration plots, and decision curve analyses were used to evaluate the nomogram model. RESULTS: Among the 72 patients who complete the follow-up, treatment-effective group and treatment-ineffective group included 42 (58.3%) and 30 (41.7%) cases, respectively. The patients in the treatment-effective group exhibited higher mean platelet volume (MPV) [(11.0 ± 1.0) fl vs. (9.8 ± 1.0) fl, P < 0.01] and platelet distribution width [12.7% (12.3%, 14.3%) vs. 11.3% (10.2%, 12.2%), P < 0.01] than those in the treatment-ineffective group. The sex ratio was significantly different (P = 0.046). A fit model comprising age [odds ratio (OR) = 0.766, 95% confidence interval (CI) = 0.594-0.987] and MPV (OR = 5.613, 95% CI = 2.297-13.711) might predict therapeutic efficacy. The area under the curve of the ROC and PR curves was computed to be 0.85 and 0.9, respectively. The P value of the Hosmer-Lemeshow test was 0.27. The decision curve analysis confirmed that managing children with VVS based on the predictive model led to a net advantage ranging from 0.01 to 0.58. The nomogram is convenient for clinical applications. CONCLUSION: A novel nomogram based on age and MPV can predict the therapeutic benefits of metoprolol in children with VVS.

Advancements in Stimulus-Responsive Co-Delivery Nanocarriers for Enhanced Cancer Immunotherapy.

Cancer immunotherapy has emerged as a novel therapeutic approach against tumors, with immune checkpoint inhibitors (ICIs) making significant clinical practice. The traditional ICIs, PD-1 and PD-L1, augment the cytotoxic function of T cells through the inhibition of tumor immune evasion pathways, ultimately leading to the initiation of an antitumor immune response. However, the clinical implementation of ICIs encounters obstacles stemming from the existence of an immunosuppressive tumor microenvironment and inadequate infiltration of CD8+T cells. Considerable attention has been directed towards advancing immunogenic cell death (ICD) as a potential solution to counteract tumor cell infiltration and the immunosuppressive tumor microenvironment. This approach holds promise in transforming "cold" tumors into "hot" tumors that exhibit responsiveness to antitumor. By combining ICD with ICIs, a synergistic immune response against tumors can be achieved. However, the combination of ICD inducers and PD-1/PD-L1 inhibitors is hindered by issues such as poor targeting and uncontrolled drug release. An advantageous solution presented by stimulus-responsive nanocarrier is integrating the physicochemical properties of ICD inducers and PD-1/PD-L1 inhibitors, facilitating precise delivery to specific tissues for optimal combination therapy. Moreover, these nanocarriers leverage the distinct features of the tumor microenvironment to accomplish controlled drug release and regulate the kinetics of drug delivery. This article aims to investigate the advancement of stimulus-responsive co-delivery nanocarriers utilizing ICD and PD-1/PD-L1 inhibitors. Special focus is dedicated to exploring the advantages and recent advancements of this system in enabling the combination of ICIs and ICD inducers. The molecular mechanisms of ICD and ICIs are concisely summarized. In conclusion, we examine the potential research prospects and challenges that could greatly enhance immunotherapeutic approaches for cancer treatment.

Celastrol Elicits Antitumor Effects through Inducing Immunogenic Cell Death and Downregulating PD-L1 in ccRCC.

BACKGROUND: Targeting immunogenic cell death (ICD) is considered a promising therapeutic strategy for cancer. However, the commonly identified ICD inducers promote the expression of programmed cell death ligand 1 (PD-L1) in tumor cells, thus aiding them to evade the recognition and killing by the immune system. Therefore, the finding of novel ICD inducers to avoid enhanced PD-L1 expression is of vital significance for cancer therapy. Celastrol (CeT), a triterpene isolated from Tripterygium wilfordii Hook. F induces various forms of cell death to exert anti-cancer effects, which may make celastrol an attractive candidate as an inducer of ICD. METHODS: In the present study, bioinformatics analysis was combined with experimental validation to explore the underlying mechanism by which CeT induces ICD and regulates PD-L1 expression in clear cell renal cell carcinoma (ccRCC). RESULTS: The results showed that EGFR, IKBKB, PRKCQ and MAPK1 were the crucial targets for CeT-induced ICD, and only MAPK1 was an independent prognostic factor for the overall survival (OS) of ccRCC patients. In addition, CeT triggered autophagy and up-regulated the expressions of HMGB1 and CRT to induce ICD in 786-O cells in vitro. Importantly, CeT can down-regulate PD-L1 expression through activating autophagy. At the molecular level, CeT suppressed PD-L1 via the inhibition of MAPK1 expression. Immunologically, the core target of celastrol, MAPK1, was tightly correlated with CD8+ T cells and CD4+ T cells in ccRCC. CONCLUSION: These findings indicate that CeT not only induces ICD but also suppresses PD-L1 by down-regulating MAPK1 expression, which will provide an attractive strategy for ccRCC immunotherapy.

IL-12-Overexpressed Nanoparticles Suppress the Proliferation of Melanoma Through Inducing ICD and Activating DC, CD8+ T, and CD4+ T Cells.

Purpose: The drug resistance and low response rates of immunotherapy limit its application. This study aimed to construct a new nanoparticle (CaCO3-polydopamine-polyethylenimine, CPP) to effectively deliver interleukin-12 (IL-12) and suppress cancer progress through immunotherapy. Methods: The size distribution of CPP and its zeta potential were measured using a Malvern Zetasizer Nano-ZS90. The morphology and electrophoresis tentative delay of CPP were analyzed using a JEM-1400 transmission electron microscope and an ultraviolet spectrophotometer, respectively. Cell proliferation was analyzed by MTT assay. Proteins were analyzed by Western blot. IL-12 and HMGB1 levels were estimated by ELISA kits. Live/dead staining assay was performed using a Calcein-AM/PI kit. ATP production was detected using an ATP assay kit. The xenografts in vivo were estimated in C57BL/6 mice. The levels of CD80+/CD86+, CD3+/CD4+ and CD3+/CD8+ were analyzed by flow cytometry. Results: CPP could effectively express EGFP or IL-12 and increase ROS levels. Laser treatment promoted CPP-IL-12 induced the number of dead or apoptotic cell. CPP-IL-12 and laser could further enhance CALR levels and extracellular HMGB1 levels and decrease intracellular HMGB1 and ATP levels, indicating that it may induce immunogenic cell death (ICD). The tumors and weights of xenografts in CPP-IL-12 or laser-treated mice were significantly reduced than in controls. The IL-12 expression, the CD80+/CD86+ expression of DC from lymph glands, and the number of CD3+/CD8+T or CD3+/CD4+T cells from the spleen increased in CPP-IL-12-treated or laser-treated xenografts compared with controls. The levels of granzyme B, IFN-γ, and TNF-α in the serum of CPP-IL-12-treated mice increased. Interestingly, CPP-IL-12 treatment in local xenografts in the back of mice could effectively inhibit the growth of the distant untreated tumor. Conclusion: The novel CPP-IL-12 could overexpress IL-12 in melanoma cells and achieve immunotherapy to melanoma through inducing ICD, activating CD4+ T cell, and enhancing the function of tumor-reactive CD8+ T cells.

Circ-Bptf Ameliorates Learning and Memory Impairments via the miR-138-5p/p62 Axis in APP/PS1 Mice.

Alzheimer's disease (AD) is a common age-associated progressive neurodegenerative disorder that is implicated in the aberrant regulation of numerous circular RNAs (circRNAs). Here, we reported that circ-Bptf, a conserved circRNA derived from the Bptf gene, showed an age-dependent decrease in the hippocampus of APP/PS1 mice. Overexpression of circ-Bptf significantly reversed dendritic spine loss and learning and memory impairment in APP/PS1 mice. Moreover, we found that circ-Bptf was predominantly localized to the cytoplasm and upregulated p62 expression by binding to miR-138-5p. Furthermore, the miR-138-5p mimics reversed the decreased expression of p62 induced by the silencing of circ-Bptf. Together, our findings suggested that circ-Bptf ameliorated learning and memory impairments via the miR-138-5p/p62 axis in APP/PS1 mice. It may act as a potential player in AD pathogenesis and therapy.

The contact force between lunar-based equipment and lunar soil.

Lunar-based equipment plays a vital role in the exploration of the moon because it undertakes the tasks of moving, transporting, digging, and so on. In order to control the gait of lunar-based equipment more precisely and guarantee mobile stability, the contact mechanism between its foot and lunar soil is worthy of in-depth study. In this paper, a contact model is proposed to predict the stress, strain, and displacement both on the contact surface and in the lunar soil when the foot is under vertical load. The axial stress in the proposed contact model is verified through the experiment and its accuracy in the lunar equipment is verified through simulation. The error is in a reasonable range and the influence depth of load conforms to the experiment results. This paper provides a relatively accurate model to describe the contact force between the lunar-based equipment's foot and the lunar soil and will promote the research of lunar exploration.

Moral sensitivity and caring behavior in nursing interns: the mediating role of empathy.

Background: The main purpose of this study is to analyze the relationship between moral sensitivity, empathy, and caring behaviors and to explore the mediating effect of empathy on moral sensitivity and caring behaviors of nursing interns. Methods: A cross-sectional survey was conducted from August to September 2022 in which 261 nursing interns from two Grade 3A Hospitals in Xi'an participated. The questionnaires used in the survey include the General Information Questionnaire (GIQ), the Moral Sensitivity Questionnaire-Revised Version translated into Chinese (MSQ R-CV), the Chinese version of the Jefferson Empathy Scale (JSE), and the Chinese version of the Caring Behavior Inventory (C-CBI). The obtained data were analyzed through descriptive statistics, a one-way analysis of variance (ANOVA), and Pearson's correlation coefficient, and the mediating effect of empathy was tested through structural equations. Results: The overall mean of moral sensitivity of nursing interns in two Grade 3A Hospitals in Xi'an is 40.84 ± 8.73, the overall mean of empathy is 100.51 ± 21.56, and the overall mean of caring behavior is (113.81 ± 21.05). Statistical analysis showed that there is a positive correlation between moral sensitivity and caring behavior of nursing interns (r = 0.376, p < 0.01), between their empathy and moral sensitivity (r = 0.336, p < 0.01), and between their empathy and caring behavior (r = 0.394, p < 0.01). The empathy of nursing interns has a mediated effect on the relationship between moral sensitivity and caring behavior. The mediated effect value was 0.14, accounting for 31.82% of the total effect. Conclusion: The moral sensitivity of nursing interns can have a direct impact on predicting the caring behavior and indirect influences their caring behaviors mediated by empathy, with the latter effect being mediated by empathy. Therefore, nursing educators and hospital administrators should adopt targeted interventions to improve the moral sensitivity and empathy of nursing interns, which can further prove to be beneficial in improving their caring behaviors, leading to enhanced quality of nursing care and reduced nurse-patient conflicts and finally to a stabilized nursing team.

Prevalence of thalassemia-carrier couples and fertility risk assessment.

Thalassemia is a highly prevalent hematologic disease in Guizhou, China. This study aimed to determine the epidemiological characteristics of thalassemia in couples at childbearing age and assess the neonatal risk of thalassemia in this subpopulation. A cohort of 4481 couples at childbearing age were recruited for thalassemia carrier screening by both traditional hematological tests and next-generation sequencing. Of them, 1314 (14.66%) thalassemia carriers were identified, including 857 (9.76%) α-thalassemia, 391 (4.36%) ß-thalassemia, and 48 (0.54%) composite α and ß-thalassemia. A total of 12 α-globin gene alterations and 16 ß-globin mutations were detected, including four novel thalassemia mutations. SEA was the most common α-thalassemia genotype (26.86%), CD41-42 the most common ß-thalassemia genotype (36.57%), and αα/- α3.7 + CD41-42 the most common composite α- and ß-thalassemia genotype (18.75%). Ethnically, the Zhuang had the highest rate of thalassemia gene carriers among the ethnic groups. Geographically, Qiannan had the highest rate of thalassemia gene carriers. In addition, 38 of the 48 couples with composite α- and ß-thalassemia were high-risk thalassemia carriers, and 4 carrying the -SEA/αα gene needed fertility guidance.

m6A-methylated KCTD21-AS1 regulates macrophage phagocytosis through CD47 and cell autophagy through TIPR.

Blocking immune checkpoint CD47/SIRPα is a useful strategy to engineer macrophages for cancer immunotherapy. However, the roles of CD47-related noncoding RNA in regulating macrophage phagocytosis for lung cancer therapy remain unclear. This study aims to investigate the effects of long noncoding RNA (lncRNA) on the phagocytosis of macrophage via CD47 and the proliferation of non-small cell lung cancer (NSCLC) via TIPRL. Our results demonstrate that lncRNA KCTD21-AS1 increases in NSCLC tissues and is associated with poor survival of patients. KCTD21-AS1 and its m6A modification by Mettl14 promote NSCLC cell proliferation. miR-519d-5p gain suppresses the proliferation and metastasis of NSCLC cells by regulating CD47 and TIPRL. Through ceRNA with miR-519d-5p, KCTD21-AS1 regulates the expression of CD47 and TIPRL, which further regulates macrophage phagocytosis and cancer cell autophagy. Low miR-519d-5p in patients with NSCLC corresponds with poor survival. High TIPRL or CD47 levels in patients with NSCLC corresponds with poor survival. In conclusion, we demonstrate that KCTD21-AS1 and its m6A modification promote NSCLC cell proliferation, whereas miR-519d-5p inhibits this process by regulating CD47 and TIPRL expression, which further affects macrophage phagocytosis and cell autophagy. This study provides a strategy through miR-519-5p gain or KCTD21-AS1 depletion for NSCLC therapy by regulating CD47 and TIPRL.

Pretreatment with long-acting gonadotropin-releasing hormone agonists improved pregnancy outcomes after hysteroscopic multiple polypectomies: A retrospective study of 660 frozen-thawed embryo transfer cycles.

OBJECTIVE: To compare the reproductive pregnancy outcomes of pretreatment with long-acting gonadotropin-releasing hormone agonist (GnRH-a) plus hormone replacement therapy (HRT) with HRT-only cycles, and investigate differences between single polypectomy and multiple polypectomies, and between one or two doses of GnRH-a. MATERIALS AND METHODS: This was a retrospective cohort study on patients undergoing polypectomy who underwent frozen-thawed embryo transfer (FET) from March 2018 to May 2019. They were divided into GnRH-a pretreatment and HRT-only groups. Each group was divided into single polypectomy or multiple polypectomies (in a single hysteroscopic session) subgroups. Clinical pregnancy rate and live birth rate (LBR) were the main outcomes. The effect of GnRH-a dosage was further analysed. RESULTS: There were 212 GnRH-a pretreatment cases (45 single and 167 multiple polyps) and 448 HRT-only cases (228 single and 220 multiple polyps). The LBR of the GnRH-a pretreatment group (53.3%) was significantly higher than the HRT group (43.3%; P = 0.016). Logistic regression analysis showed that GnRH-a pretreatment significantly affected the LBR (odds ratio, OR 1.470, 95% confidence interval, Cl 1.046-2.065; P = 0.026). In the multiple polypectomy subgroup, the LBR with GnRH-a pretreatment was higher than with HRT-only (54.5% vs 43.6%; P = 0.034). However, the LBR was not different between the respective single polypectomy subgroups (48.9% vs 43.0%; P = 0.466). For patients with multiple polyps, two GnRH-a pretreatments produced a higher LBR than a single GnRH-a pretreatment (62.7% vs 47.8%), but without significant difference (P = 0.055). CONCLUSION: GnRH-a pretreatment improved the LBR for FET cycles after hysteroscopic multiple polypectomies, independent of dose.

Observation of Emergent Superconductivity in the Topological Insulator Ta2Pd3Te5 via Pressure Manipulation.

Topological insulators offer significant potential to revolutionize diverse fields driven by nontrivial manifestations of their topological electronic band structures. However, the realization of superior integration between exotic topological states and superconductivity for practical applications remains a challenge, necessitating a profound understanding of intricate mechanisms. Here, we report experimental observations for a novel superconducting phase in the pressurized second-order topological insulator candidate Ta2Pd3Te5, and the high-pressure phase maintains its original ambient pressure lattice symmetry up to 45 GPa. Our in situ high-pressure synchrotron X-ray diffraction, electrical transport, infrared reflectance, and Raman spectroscopy measurements, in combination with rigorous theoretical calculations, provide compelling evidence for the association between the superconducting behavior and the densified phase. The electronic state change around 20 GPa was found to modify the topology of the Fermi surface directly, which synergistically fosters the emergence of robust superconductivity. In-depth comprehension of the fascinating properties exhibited by the compressed Ta2Pd3Te5 phase is achieved, highlighting the extraordinary potential of topological insulators for exploring and investigating high-performance electronic advanced devices under extreme conditions.