Selecting mode by the complex Berry phase in non-Hermitian waveguide lattices.

Bloch oscillations (BOs) in a parity-time (PT)-symmetric Su-Schrieffer-Heeger (SSH) waveguide array are theoretically investigated. We show that the BOs are amplified or damped even for the systems to exhibit entirely real energy bands. The amplified and damped BOs stem from the complex Berry phase and closely relate to the topological properties of the lattice. For the topological nontrivial lattice, the amplification and attenuation of BOs are much more prominent than the trivial case and the output Bloch mode can be selected. Furthermore, we propose an experimental scheme and perform a numerical simulation based on a bent waveguide array. Our work uncovers the impact of the topological properties on the dynamics of the bulk Bloch modes and unveils a horizon in the study of non-Hermitian physics. The mode selection induced by the complex Berry phase may also find application in integrated photonic devices such as the mode filter.

Circ_0020460 drives tumorigenesis in cervical cancer through miR-485-3p sponging.

Deregulation of circular RNAs (circRNAs) is widely recognized in cancer progression. Our study aims to investigate the role of circ_0020460 in the development of cervical cancer (CC) and its potential mechanism of action. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot assays were used to detect the expression levels of circ_0020460, miR-485-3p and C-X-C motif chemokine ligand 1 (CXCL1). The roles of circ_0020460 on cell proliferation, cell migration, cell invasion, cell apoptosis, and angiogenesis were investigated using cell counting kit-8 (CCK-8) and Ethynyl deoxyuridine (Edu) assay, wound healing assay, transwell assay, flow cytometry assay, and tube formation assay, respectively. The putative relationship predicted by bioinformatics analysis was verified by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Xenograft models were constructed to explore the role of circ_0020460 in vivo. The expression of circ_0020460 and CXCL1 expression were increased, while miR-485-3p expression was declined in CC tissues and cells. Circ_0020460 knockdown suppressed CC cell proliferation, cell migration, cell invasion, angiogenesis, and promoted cell apoptosis. Circ_0020460 functioned as a miR-485-3p sponge to inhibit miR-485-3p level, and the anti-cancer effects mediated by circ_0020460 knockdown were reversed by miR-485-3p inhibitor. MiR-485-3p bound to CXCL1 3' untranslated region (3'UTR) to degrade CXCL1 expression, and the anti-cancer effects of miR-485-3p restoration were impaired by CXCL1 overexpression. Circ_0020460 downregulation inhibited CC xenograft tumor growth. These results suggest that circ_0020460 promoted the malignant behavior of CC cells by modulating the miR-485-3p/CXCL1 axis.

Overlapping lockup lymphaticovenous anastomosis: A useful addition to supermicrosurgery.

BACKGROUND: Lymphaticovenular anastomosis (LVA) is a minimally invasive surgical procedure used to treat lymphedema. This surgical procedure connects the superficial lymphatic vessels to nearby veins to establish lymphatic-venous pathways. One of the most common challenges encountered by lymphatic surgeons when performing LVA is a mismatch in the sizes of the veins and lymphatic vessels, with the effectiveness limited by technical constraints. We conducted a pilot study to evaluate the feasibility of an overlapping lockup anastomosis (OLA) LVA technique to address these problems. METHODS: In this study, we present a novel OLA technique for LVA that addresses the challenges with conventional techniques. The OLA technique was used in 10 lymphedema patients between September 2022 and March 2023 to compare OLA and end-to-end anastomosis. The time required for anastomosis, method of anastomosis, patency rates, and lymphedema volume were evaluated in this study. RESULTS: Of 123 LVAs, 44 were performed using the OLA technique in 10 patients, with indocyanine green lymphangiography revealing unobstructed drainage. A single case of slight fluid leakage occurred, which was resolved by reinforcing the sutures. The average anastomosis time for OLA and the end-to-end technique was 5.55 minutes and 12.1 minutes, respectively. The wounds of the patients healed without infection, and the subjective limb circumference decreased. CONCLUSIONS: The OLA technique could serve as a valuable addition to the current LVA technique, especially for cases with a mismatch in the sizes of the lymphatic vessels and veins. This technique has the potential to promote the broader application of LVA in the treatment and prevention of lymphedema.

Candida causes recurrent vulvovaginal candidiasis by forming morphologically disparate biofilms on the human vaginal epithelium.

Background: Recurrent vulvovaginal candidiasis (RVVC) is a recalcitrant medical condition that affects many women of reproductive age. The importance of biofilm formation by Candida in RVVC has been recently questioned. This study aimed to elucidate the fundamental growth modes of Candida in the vagina of patients with RVVC or sporadic vulvovaginal candidiasis (VVC) and to assess their roles in the persistence of RVVC. Methods: Vaginal tissues were sampled from twelve patients clinically and microbiologically diagnosed as RVVC or VVC at a post-antifungal-treatment and asymptomatic period. High-resolution scanning electron microscopy, fluorescence in situ hybridization in combination with Candida-specific 18S rRNA probes and viable fungal burden were used to qualitatively and quantitatively evaluate Candida growth in the human vagina. The presence of Candida biofilm extracellular polymeric substances was examined using confocal laser scanning microscopy and biopsy sections pre-stained with Concanavalin A. Histopathological analysis was carried out on infected vaginal tissues stained with hematoxylin and eosin. Lastly, the susceptibility of epithelium-associated Candida biofilms to fluconazole at the peak serum concentration was evaluated. Results: Candida species grew on the vaginal epithelium of RVVC patients as morphologically disparate biofilms including monolayers, microcolonies, and macro-colonies, in addition to sporadic adherent cells. Candida biofilm growth on the vaginal epithelium was associated with mild lymphocytic infiltration of the vaginal mucosa. These epithelium-based Candida biofilms presented an important characteristic contributing to the persistence of RVVC that is the high tolerance to fluconazole. Conclusions: In summary, our study provides direct evidence to support the presence of Candida biofilms in RVVC and an important role of biofilm formation in disease persistence.

Photonic skin-topological effects in microring lattices.

We investigate the non-Hermitian Hofstadter-Harper model composed of microring resonators, in which the non-Hermitian skin effect (NHSE) is particularly analyzed. The effect is achieved through the interaction between well-designed gain-loss layouts and artificial gauge fields. Remarkably, we reveal the emergence of a hybrid skin-topological effect (HSTE), where only the original topological edge modes convert to skin modes while bulk modes remain extended. By changing the distributions of gauge fields, we show the NHSE can manifest itself in bulk modes and be localized at specific edges. Using the equivalence of sites in the bulk or at boundaries to 1D SSH chains, we analyze the potential cancellation of NHSE in these configurations. Additionally, we demonstrate a new, to the best of our knowledge, type of HSTE in topological insulators which emerge at any gain-loss interfaces. The study may improve the understanding of the NHSE behavior in 2D topological systems and provide a promising avenue for tuning light propagation and localization.

Influence of psychological capital on core competency for new nurses.

BACKGROUND: The development of core competency is crucial for the success of new nurses, enabling them to deliver high-quality care. Psychological capital (PsyCap), encompassing self-efficacy, optimism, hope, and resilience, significantly influences individuals' abilities and achievements across various professions. However, limited research has specifically examined the impact of PsyCap on the core competency of new nurses. This study aims to bridge this gap by investigating the relationship between PsyCap and core competency development in new nurses, providing valuable strategic insights for improving PsyCap and promoting core competence acquisition. METHODS: 142 new nurses were chosen for the investigation using a convenient cluster sampling method. The questionnaire included components on socio-demographic characteristics, the Competency Inventory for Registered Nurses (CIRN), and the PsyCap Questionnaire-24 (PCQ-24). The t-test, One-Way ANOVA, Pearson correlation analysis and hierarchical multiple regression were used for statistical analysis. RESULT: The number of valid questionnaires was 138, and the effective return rate was 97.2%. The overall mean score for core competencies was 171.01 (SD 25.34), and the PsyCap score was 104.76(SD 13.71). The PsyCap of new nurses was highly correlated with core competency, with a correlation coefficient of r = 0.7, p < 0.01. Self-efficacy of PsyCap is a significant independent predictor of core competency (adjust R2 = 0.49). CONCLUSION: Self-efficacy in PsyCap is an important predictor of new nurses' core competency. Nursing managers should pay sufficient attention to the cultivation and development of new nurses' PsyCap, with particular emphasis on enhancing self-efficacy to improve their core competency.

Multidimensional synthetic frequency lattice in the dynamically modulated waveguides.

Here we propose an effective method to construct a higher-dimensional synthetic frequency lattice with an optical waveguide under dynamic modulation. By applying the traveling-wave modulation of refractive index modulation with two different frequencies that are not mutually commensurable, a two-dimensional frequency lattice could be formed. The Bloch oscillations (BOs) in the frequency lattice is demonstrated by introducing a wave vector mismatch of the modulation. We show that the BOs are reversible only as the amounts of wave vector mismatch in orthogonal directions are mutually commensurable. Finally, by employing an array of waveguides with each under traveling-wave modulation, a 3D frequency lattice is formed and its topological effect of one-way frequency conversion is revealed. The study offers a versatile platform for exploring higher-dimensional physics in concise optical systems and may find great application in optical frequency manipulations.

The complete mitochondrial genome of Choristoneura metasequoiacola Liu,1983 (Lepidoptera: Tortricidae).

Choristoneura metasequoiacola Liu, 1983 is an important caterpillar species that specifically infests the leaves and branches of Metasequoia glyptostroboides Hu & W. C. Cheng 1948 with short larval infestations, long-term dormancy, and has a limited distribution in Lichuan, Hubei, China. The complete mitochondria genome of C. metasequoiacola was determined by using Illumina NovaSeq, and analyzed based on previously annotated sibling species. In total, we obtained mitochondria genome with 15,128 bp in length, circular in shape with a double-stranded closed ring structure, including 13 protein-coding genes, 2 rRNA genes, 22 tRNA genes, and an AT-rich region. Of which the nucleotide composition was highly A + T biased, accounting for 81.98% of the whole mitogenome. Thirteen protein-coding genes (PCGs) were 11,142 bp; Twenty-two tRNA genes and AT-rich region were 1,472 and 199 bp, respectively. Phylogenetically, the relationship between Choristoneura spp. (containing C. metasequoiacola) and Adoxophyes spp. was closer than any other two genera from Tortricidae, and the relationship between C. metasequoiacola and C.murinana was the closest among nine sibling species from that genus, which helps to explain species evolution within the family Tortricidae.

Subsequent fertility after cesarean scar pregnancy: a retrospective analysis.

BACKGROUND: Cesarean scar pregnancy (CSP) refers to the implantation and growth of the gestational sac at a uterine scarring site due to a previous cesarean section. The effects of CSP on subsequent fertility have emerged as a clinical issue of importance in gynecology and obstetrics in China owing to the increasing rate of cesarean section over the past 30 years in combination with the abolition of the national family planning policy, allowing for subsequent pregnancies. Therefore, we aimed to investigate the effects of CSP treatment on subsequent fertility and pregnancy outcomes. METHODS: The study consecutively enrolled 499 women treated for CSP at Taizhou Hospital between January 2009 and December 2018. The study outcomes were the rate of secondary infertility and pregnancy outcomes. Clinical information was collected at the time of admission for CSP treatment. Information on subsequent fertility and pregnancy outcomes was collected via telephonic follow-up. RESULTS: Among the 499 women who met the inclusion criteria for CSP, 48 were lost to follow-up. Most women (74.9%, 338/451) did not express the desire for a subsequent pregnancy after CSP treatment. Among the 113 women who initially desired a subsequent pregnancy, 62 finally abandoned fertility plans. Among the 51 women who pursued pregnancy, 48 pregnancies were recorded in 43 women, infertility secondary to CSP treatment was identified in 15.7% (8/51) of women, and 60.8% (31/51) of women achieved full-term pregnancy, with placenta accreta spectrum identified in two women, one requiring a hysterectomy during cesarean section due to massive bleeding. Among the 16 women treated with uterine artery embolization combined with uterine aspiration and 18 women treated by ultrasound-guided local lauromacrogol injection combined with uterine aspiration, a successful full-term pregnancy rate of 68.8% (11/16) and 88.9% (16/18), respectively, was achieved. There were five cases of recurrent CSP among all 76 pregnancies (6.6%). CONCLUSION: Over a long-term follow-up of women after CSP treatment, a high successful fertility rate was identified, with also an increased CSP recurrence rate. Uterine artery embolization combined with uterine aspiration and ultrasound-guided local lauromacrogol injection combined with uterine aspiration showed high rates of successful post-treatment fertility and pregnancy.

Squalene epoxidase facilitates cervical cancer progression by modulating tumor protein p53 signaling pathway.

BACKGROUND: The mortality of cervical cancer (CC) is quite high and advanced CC is hard to cure. Accordingly, to find the mechanism of CC progression at molecular level is imminent. METHODS: The mRNA expression data were acquired from The Cancer Genome Atlas database, and squalene epoxidase (SQLE) level in the tumor and adjuvant tissues of CC was analyzed. The pathway enrichment analysis of target mRNAs was performed based on the GSEA database. The cancerous tissues and para-cancerous tissues of CC patients were collected for immunohistochemistry. SQLE and p53 mRNA expression was ensured by qRT-polymerase chain reaction. SQLE and p53 protein levels were determined by western blot. Cell functional assays focused on evaluating the malignant behaviors of cancer cells in each treatment group. Nude mouse xenograft models were constructed for tumorigenicity analysis. RESULTS: Bioinformatics analysis revealed that SQLE expression was high in CC tissues, which was linked to the poor prognosis. SQLE could affect the p53 signaling pathway. Cell functional assays demonstrated that SQLE expression was promoted in CC cell lines, and overexpressing SQLE facilitated the malignant phenotypes of CC cells, whereas silencing SQLE suppressed CC progression in vitro and in vivo. Besides, the repressed p53 signaling pathway could reverse the effect caused by silenced SQLE. CONCLUSION: SQLE could promote CC progression by modulating the p53 signaling pathway.

Circ_0042986 Presence Restrains Cervical Cancer Development via Upregulating PEG3 by Directly Targeting miR-582-3p.

The participation of circular RNAs (circRNAs) in carcinogenesis is widely established. Numerous circRNAs with aberrant expression in cervical cancer (CC) are identified by RNA sequencing, whereas the function of these circRNAs remains unclear. We thus aimed to unveil the effects and mechanisms of circ_0042986 in CC. Circ_0042986 with aberrant downregulation in CC was obtained from GSE10286 dataset. qPCR and western blotting were employed for the detection of circ_0042986, miR-582-3p, and paternally expressed 3 (PEG3) expressions. EdU assay, colony formation assay, wound healing assay, transwell assay, tube formation assay, and flow cytometry assay were applied for functional analyses. The potential binding site was ensured by dual-luciferase reporter analysis, and their binding relationship was verified by pull-down assay. The transplanted tumor models were constructed for in vivo function verification of circ_0042986. Our findings exposed that the downregulation of circ_0042986 was verified in clinical CC samples. Circ_0042986 overexpression largely attenuated CC cell growth, invasiveness, angiogenesis, and survival. MiR-582-3p was targeted by circ_0042986, and the inhibitory roles of circ_0042986 presence were partly abolished by miR-582-3p enrichment. MiR-582-3p combined with PEG3, and circ_0042986 increased PEG3 expression via decoying miR-582-3p. The interaction between miR-582-3p and PEG3 on CC cell functions was confirmed, evidenced by the reversal effects of PEG3 knockdown on miR-582-3p deficiency-inhibited cancer cell malignant behaviors. Circ_0042986 overexpression also limited tumorigenesis of CC in animal models. In summary, circ_0042986 overexpression decoyed miR-582-3p to increase PEG3 expression, thereby blocking the malignant progression of CC.

Systematic Pan-Cancer Analysis and Experimental Verification Identify FOXA1 as an Immunological and Prognostic Biomarker in Epithelial Ovarian Cancer.

Background: Epithelial ovarian cancer (EOC) has the lowest survival rate among female reproductive cancers present with symptoms of aggressive malignancies, poor prognosis, drug resistance and postoperative recurrence. The majority of patients with EOC are diagnosed at an advanced stage due to the therapeutic challenges including lack of early diagnosis and effective therapeutic targets for EOC. Methods: Pan-cancer analyses were performed to explore the features of forkhead-box (FOX) A1 (FOXA1) using data from TCGA and GTEx databases. R package "clusterprofiler" was used to perform the enrichment analysis of FOXA1 in EOC. Data downloaded from Drug Sensitivity in Cancer (GDSC) database were used to evaluate the association between FOXA1 and antitumor drug sensitivity. In experimental verification, FOXA1 expression was detected using qRT-PCR and western blot assays. Western blot, immunofluorescence staining, and Transwell assays were used to assess the influence of FOXA1 silencing on epithelial-mesenchymal transition (EMT) of EOC cells. Results: We found that FOXA1 was highly expressed in EOC and predicted poorer survival of EOC patients. We observed that FOXA1 expression was positively correlated EMT-related pathways. Through experimental verification, we found the underlying function of FOXA1 to promote EMT in ovarian cancers. The results from western blot, immunofluorescence staining, and Transwell assays showed that FOXA1 silencing impeded the progression of EMT and invasiveness of the cancer cells. Furthermore, CCK-8 and invasion assays suggested that siRNA-FOXA1 attenuated the ability of cancer cells to metastasize and proliferate. Dual-luciferase reporter assays confirmed the binding activity of FOXA1 to the promoter of connective tissue growth factor (CTGF). In addition, we found that FOXA1 was closely correlated immunosuppressive microenvironment of EOC. High FOXA1 expression may contribute to the resistance of many anticancer drugs. Conclusions: Our results predict and validate the function of FOXA1 in promoting EMT and the progression of disease in EOC. Targeting FOXA1 may improve the sensitivity of EOC treatment.

Methodology of designing compact schlieren systems using off-axis parabolic mirrors.

Schlieren imaging is widely adopted in applications where fluid dynamics features are of interest. However, traditional Z-type schlieren systems utilizing on-axis mirrors generally require large system footprints due to the need to use high f-number mirrors. In this context, off-axis parabolic (OAP) mirrors provide an attractive alternative for permitting the use of smaller f-number optics, but well-documented methodologies for designing schlieren systems with OAP mirrors are lacking. The present work outlines a ray-tracing-based workflow applied to the design of a modified Z-type schlieren system utilizing OAP mirrors. The ray-tracing analysis evaluates the defocus and distortion introduced by schlieren optics. The results are used along with system size and illumination efficiency considerations to inform the selection of optimal optical components capable of producing high-quality schlieren images while minimizing the system footprint. As a step-by-step demonstration of the design methodology, an example schlieren system design is presented. The example schlieren design achieved an image resolution of 1.1 lp/mm at 50% contrast, with a 60% reduction in system length compared to traditional Z-type systems with f/8 mirrors; distortion characterizations of the designed schlieren system showed good agreement with ray-tracing predictions, and the distortion can be corrected through image post-processing. The current work provides a systematic approach for the design of compact schlieren systems with OAP mirrors and demonstrates the utility of this underutilized option.

Chiral Zener tunneling in non-Hermitian frequency lattices.

A waveguide coupler under both phase and intensity modulation is proposed to generate a non-Hermitian Su-Schrieffer-Heeger lattice in frequency dimension. By varying the modulation period and phase, we can manipulate the on-site potential of the lattice and realize anisotropic coupling of the supermodes in waveguides. The artificial electric field associated with the modulation phase can also be introduced simultaneously. Zener tunneling is demonstrated in the non-Hermitian system and manifests an irreversibly unidirectional conversion between odd and even supermodes. The conversion efficiency can be optimized by varying the on-site potential of the waveguides. The study provides a versatile platform to explore non-Hermitian multiband physics in synthetic dimensions, which may find great application in chiral mode converters and couplers.

The efficacy of different treatments for type 2 cesarean scar pregnancy.

OBJECTIVE: To study the efficacy of 3 treatment options for type 2 cesarean scar pregnancy (CSP) and establish an optimal treatment strategy for type 2 CSP. DESIGN: Retrospective cohort study. SETTING: A tertiary hospital. PATIENTS: The study examined 160 women with type 2 CSP. INTERVENTIONS: Ultrasound-guided vacuum aspiration after local injection of lauromacrogol, ultrasound-guided vacuum aspiration after uterine artery embolization (UAE), and transabdominal resection or hysteroscopy combined with laparoscopic resection. MAIN OUTCOME MEASURES: The success rates, duration of hospitalization, hospitalization cost, amount of blood loss, recovery time, and menstruation resuming after recovery. RESULTS: The success rates of the UAE, lauromacrogol, and surgical groups were 87.1%, 92.5%, and 95.5%, respectively, with no significant differences. The cost and duration of hospitalization in the lauromacrogol group were significantly lower than those in the UAE and surgical groups. Analysis of the causes of treatment failure revealed a significant difference in the gestational age. The area under the receiver operating characteristic curve was 0.660 (95% confidence interval, 0.533-0.788). When the gestational age was 48.5 days, Youden index was the highest. Furthermore, when the diagnostic thresholds were selected as 49, 56, and 63 days of pregnancy, the corresponding areas under the receiver operating characteristic curve were 0.652, 0.541, and 0.510, respectively. CONCLUSION: Ultrasound-guided vacuum aspiration after local injection of lauromacrogol is recommended for patients with type 2 CSP at <49 days of gestation. Laparotomy or laparoscopy combined with hysteroscopy is suitable for patients with gestation of >49 days, especially for those with >56 days of gestation.

The Efficacy and Health Economics of Different Treatments for Type 1 Cesarean Scar Pregnancy.

Objectives: To evaluate the efficacy and health economics of four treatments for type 1 cesarean scar pregnancy (CSP). Methods: From January 2009 to December 2018, 326 patients diagnosed with type 1 CSP were examined, among whom 31 received ultrasound-guided local injection of methotrexate (local injection group), 160 patients received uterine artery embolization combined with suction aspiration (UAE group), 25 patients received ultrasound-guided suction aspiration (aspiration group) and 90 received ultrasound-guided local injection of lauromacrogol combined with suction aspiration (lauromacrogol group). Clinical data and outcomes were analyzed. The decision tree model was used to compare the economics of four treatments. Results: The success rate of the local injection group was 71.0% (22/31), which was significantly different from 98.8% (158/160) of the UAE group and 100.0% (90/90) of the lauromacrogol group. The success rate of the aspiration group was 92.0% (23/25), which was significantly lower than that of the lauromacrogol group. The cost-effectiveness ratio was 1,876.53 yuan for the aspiration group, 2,164.63 yuan for the lauromacrogol group, 4,383.56 yuan for the local injection group, and 7,850.81 yuan for the UAE group. The Incremental cost effectiveness ratio (ICER) of the lauromacrogol group to the aspiration group was 5,477.75 yuan, indicating that if the willing to pay of patients was higher than 5,477.75 yuan, the lauromacrogol group had a cost-effectiveness advantage in treating type 1 CSP, compared to aspiration group. On the contrary, aspiration group has a higher cost-effectiveness advantage. The ICER of the lauromacrogol group to the local injection group or the UAE group were both less than 0, indicating that local injection group and UAE group was not cost-effective in the treatment of type 1 CSP. Conclusion: For type 1 CSP, the ultrasound-guided local injection of lauromacrogol combined with suction aspiration and ultrasound-guided suction aspiration, are effective and economical, and the choice between the two can be based on the patient's willing to pay.

Frequency manipulation of topological surface states by Weyl phase transitions.

By creating a synthetic frequency dimension with dynamic modulation in a 2D honeycomb waveguide array, we construct both Type-I and Type-II Weyl semimetals (WSMs) and utilize the WSM phase transition to control the frequency evolutions of topological surface states. We show that Type-I WSMs and Type-II WSMs manifest opposite and same band slopes for the two surface states, which give rise to the bidirectional and unidirectional frequency shifts, respectively. Moreover, by cascading Type-I Weyl lattices and Type-II Weyl lattices together, we also achieve the time-reversed evolution of frequency, such as frequency negative refraction, bandwidth expansion-compression, and perfect imaging. The Letter may find applications in robust signal transmission and processing with synthesized topological states.

TRPV4 is a Prognostic Biomarker that Correlates with the Immunosuppressive Microenvironment and Chemoresistance of Anti-Cancer Drugs.

Background: Transient receptor potential cation channel subfamily V member 4 (TRPV4) has been reported to regulate tumor progression in many tumor types. However, its association with the tumor immune microenvironment remains unclear. Methods: TRPV4 expression was assessed using data from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) database. The clinical features and prognostic roles of TRPV4 were assessed using TCGA cohort. Gene set enrichment analysis (GSEA) of TRPV4 was conducted using the R package clusterProfiler. We analyzed the association between TRPV4 and immune cell infiltration scores of TCGA samples downloaded from published articles and the TIMER2 database. The IC50 values of 192 anti-cancer drugs were downloaded from the Genomics of Drug Sensitivity in Cancer (GDSC) database and the correlation analysis was performed. Results: TRPV4 was highly expressed and associated with worse overall survival (OS), disease-specific survival (DSS), disease-free interval (DFI), and progression-free interval (PFI) in colon adenocarcinoma (COAD) and ovarian cancer. Furthermore, TRPV4 expression was closely associated with immune regulation-related pathways. Moreover, tumor-associated macrophage (TAM) infiltration levels were positively correlated with TRPV4 expression in TCGA pan-cancer samples. Immunosuppressive genes such as PD-L1, PD-1, CTLA4, LAG3, TIGIT, TGFB1, and TGFBR1 were positively correlated with TRPV4 expression in most tumors. In addition, patients with high expression of TRPV4 might be resistant to the treatment of Cisplatin and Oxaliplatin. Conclusion: Our results suggest that TRPV4 is an oncogene and a prognostic marker in COAD and ovarian cancer. High TRPV4 expression is associated with tumor immunosuppressive status and may contribute to TAM infiltration based on TCGA data from pan-cancer samples. Patients with high expression of TRPV4 might be resistant to the treatment of Cisplatin and Oxaliplatin.

Exosomes released from decidual macrophages deliver miR-153-3p, which inhibits trophoblastic biological behavior in unexplained recurrent spontaneous abortion.

BACKGROUND: Spontaneous abortion is a common disease in human pregnancy. Increasing evidence suggests that proper function of trophoblasts and immune balance of the maternal-fetal interface are crucial for successful pregnancy. Macrophages are involved in the maternal-fetal immune microenvironment. However, mechanisms associated with how macrophages impair trophoblasts' function in spontaneous abortion remain to be explored. METHODS: Firstly, the characteristics of the isolated macrophage-derived exosomes were verified by TEM and Western blot. Then, we established the co-culture of macrophage-derived exosomes with trophoblasts, and explored the role of the exosomes in trophoblasts. Moreover, expression of miR-153-3p in the macrophage-derived exosomes was detected. A miR-153-3p mimic was transfected into trophoblasts to investigate its function in the biological functions of trophoblast cells. MRNA and protein expressions were detected by qRT-PCR and Western blot. CCK8 assay was performed to measure cell proliferation and Transwell assay was utilized to examine migration of trophoblasts. RESULTS: Compared with those in normal pregnant women, decidual macrophage-derived exosomes from unexplained recurrent spontaneous abortion (URSA) patients suppressed the proliferation and migration of trophoblast cells through the IDO/STAT3 pathway. MiR-153-3p was highly expressed in exosomes released from decidual macrophages of URSA patients. Transfecting miR-153-3p mimics into trophoblast cells directly inhibited IDO genes, which suppressed STAT3 pathway activation, regulating the biological behavior of trophoblast cells. CONCLUSIONS: This study outlines the role of decidual macrophage-derived exosomal miR-153-3p in successful pregnancy maintenance, paving a new approach for the development of novel treatments for URSA.

Up-regulated lncRNA XIST contributes to progression of cervical cancer via regulating miR-140-5p and ORC1.

BACKGROUND: The study purpose was to make investigation into the influence of XIST on cervical cancer progression and what's more its potential mechanism. METHODS: The cervical cancer data sets (lncRNA, miRNA, and mRNA) obtained from TCGA were analyzed with the "mixOmics" R package. Then, the expression of XIST, miR-140-5p, and ORC1 were detected using qRT-PCR and western blot in both tissues and cervical cancer cell lines (Hela and C33A) to verify the bioinformatics analyses results. CCK-8 assay, 5-ethynyl-2'-deoxyuridine (EdU) assays, cell cycle assay and cell apoptosis assay were practiced. Besides, immunohistochemistry staining was operated for the detection of the Ki-67, E-cadherin and vimentin expression in cervical cancer tissues and the apoptosis-related proteins expression (c-caspase3, Bcl-2, total PARP and cleaved PARP) was verified through western blot. And in vivo experiments were implemented. RESULTS: MiR-140-5p was down-regulated but XIST and ORC1 were up-regulated in cervical cancer tissues and cell lines. Knocking down of the XIST or ORC1 memorably suppressed cell proliferation, blocked cell cycle, decreased the expression of Bcl-2 while increased the apoptosis rate and the expression of c-caspase3 and cleaved PARP in HeLa and C33A cells. Besides, the results of immunohistochemistry staining showed knocking down the expression of XIST improved the expression levels of E-cadherin and decreased Ki-67 and vimentin expression. And overexpression of miR-140-5p also could inhibit the progression and reverse the influence of XIST and ORC1 in HeLa and C33A cells. CONCLUSION: Our study indicated the effects of XIST/miR-140-5p/ORC1 axis on the progression of cervical cancer which will shed new light on epigenetic diagnostics and therapeutics in cervical cancer.