IGF2BP2 promotes ovarian cancer growth and metastasis by upregulating CKAP2L protein expression in an m6 A-dependent manner.

Ovarian cancer (OC) is the second leading cause of gynecological cancer-related death in women worldwide. N6-methyladenosine (m6 A) is the most abundant internal modification in eukaryotic RNA. Human insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2), an m6 A reader, can enhance mRNA stability and promote translation by recognizing m6 A modifications. Its tumor-promoting effects have been demonstrated in several cancers. However, the roles of m6 A modification and IGF2BP2 in OC remain unclear. Here, by using methylated RNA immunoprecipitation sequencing, we demonstrated that there is widespread dysregulation of m6 A modification in OC tissues. The m6 A modification and the mRNA and protein levels of IGF2BP2 were significantly elevated in OC. Overexpression of IGF2BP2 facilitated OC cell proliferation, migration, and invasion in vitro and accelerated tumor growth and metastasis in vivo. While IGF2BP2-knockdown showed the opposite effect. Mechanistically, we identified cytoskeleton-associated protein 2-like (CKAP2L) as a target of IGF2BP2. IGF2BP2 promoted CKAP2L translation dependent on m6 A modification, rather than affecting mRNA and protein stability. Overexpression of CKAP2L rescued the tumor-suppressive effect of IGF2BP2 knockdown in OC cells. In conclusion, this study revealed the potential role of IGF2BP2 in tumor progression, at least partially via promoting the translation of CKAP2L in an m6 A-dependent manner.

Tripartite-motif 3 represses ovarian cancer progression by downregulating lactate dehydrogenase A and inhibiting AKT signaling.

The E3 ubiquitin ligase Tripartite-motif 3 (TRIM3) is known to play a crucial role in tumor suppression in various tumors through different mechanisms. However, its function and mechanism in ovarian cancer have yet to be elucidated. Our study aims to investigate the expression of TRIM3 in ovarian cancer and evaluate its role in the development of the disease. Our findings revealed a significant decrease in TRIM3 mRNA and protein levels in ovarian cancer tissues and cells when compared to normal ovarian epithelial tissues and cells. Furthermore, we observed a negative correlation between the protein level of TRIM3 and the FIGO stage, as well as a positive correlation with the survival of ovarian cancer patients. Using gain and loss of function experiments, we demonstrated that TRIM3 can inhibit cell proliferation, migration and invasion of the ovarian cancer cells in vitro, as well as suppress tumor growth in vivo. Mechanistic studies showed that TRIM3 interacts with lactate dehydrogenase A, a key enzyme in the glycolytic pathway, through its B-box and coiled-coil domains and induces its ubiquitination and proteasomal degradation, leading to the inhibition of glycolytic ability in ovarian cancer cells. RNA-sequencing analysis revealed significant alterations in the phosphatidylinositol signaling pathways upon TRIM3 overexpression. Additionally, overexpression of TRIM3 inhibited the phosphorylation of AKT. In conclusion, our study demonstrated that TRIM3 exerts a tumor-suppressive effect in ovarian cancer, at least partially, by downregulating LDHA and inhibiting the AKT signaling pathway, and thus leading to the inhibition of glycolysis and limiting the growth of ovarian cancer cells.

LncRNA SLC25A21-AS1 increases the chemosensitivity and inhibits the progression of ovarian cancer by upregulating the expression of KCNK4.

Owing to high mortality rate, ovarian cancer seriously threatens women's health. Extensive abdominal metastasis and chemoresistance are the leading causes of ovarian cancer deaths. Through lncRNA sequencing, our previous study identified lncRNA SLC25A21-AS1, which was significantly downregulated in chemoresistant ovarian cancer cells. In this study, we aimed to evaluate the role and mechanism of SLC25A21-AS1 in ovarian cancer. The expression of SLC25A21-AS1 was analyzed by qRT-PCR and online database GEPIA. The biological functions of SLC25A21-AS1 and KCNK4 were analyzed by CCK-8, transwell, and flow cytometry. The specific mechanism was analyzed by RNA-sequencing, RNA binding protein immunoprecipitation, rescue experiments, and bioinformatic analysis. SLC25A21-AS1 was decreased in ovarian cancer tissues and cell lines. Overexpression of SLC25A21-AS1 enhanced the sensitivity of ovarian cancer cells to paclitaxel and cisplatin, and inhibited cell proliferation, invasion, and migration, while SLC25A21-AS1-silencing showed the opposite effect. Potassium channel subfamily K member 4 (KCNK4) was significantly up-regulated upon enforced expression of SLC25A21-AS1. Overexpression of KCNK4 inhibited cell proliferation, invasion, migration ability, and enhanced the sensitivity of ovarian cancer cells to paclitaxel and cisplatin. Meanwhile, KNCK4-overexpression rescued the promotive effect of SLC25A21-AS1-silencing on cell proliferation, invasion and migration. In addition, SLC25A21-AS1 could interact with the transcription factor Enhancer of Zeste Homolog 2 (EZH2), while EZH2 knockdown increased the expression of KCNK4 in some of the ovarian cancer cell lines. SLC25A21-AS1 enhanced the chemosensitivity and inhibited the proliferation, migration, and invasion ability of ovarian cancer cells at least partially by blocking EZH2-mediated silencing of KCNK4.

A Case-Control Study of 40 Patients with Piriformis Muscle Syndrome to Evaluate Diagnostic Findings Using Two-Dimensional Ultrasound and Shear Wave Elastography.

BACKGROUND Piriformis muscle syndrome (PMS) is a neuropathy caused by compression of the sciatic nerve by the piriformis muscle. This case-control study included 40 patients with PMS and aimed to evaluate the diagnostic findings using two-dimensional ultrasound and shear wave elastography (SWE), as non-invasive and cost-effective diagnostic methods. MATERIAL AND METHODS In order to evaluate the value of two-dimensional ultrasound diagnosis, a new imaging technique called shear wave elastography (SWE) was used in the screening of PMS, with a total of 40 PMS patients and 40 healthy individuals participating in our study. We analyzed the correlation and area under the curve (AUC) of changes in thickness (mm) and Young's modulus (kpa) of the bilateral piriformis muscle (PM). RESULTS We found that PM thickness and Young's modulus on the lesion sides were significantly higher in PMS patients than in controls (P<0.05). Also, we determined that there was a positive correlation between PM thickness and Young's modulus (r=0.454, P<0.05). Using two-dimensional ultrasonic diagnosis and the SWE technique, a specificity of 95.8% and sensitivity of 78.8% were demonstrated in the clinical diagnosis of PM. CONCLUSIONS Two-dimensional ultrasound with SWE technology has demonstrated its superior sensitivity and specificity in diagnosing PMS in the clinic.

Effects of "Shi Ying Zi" powder and osthole on immune and antioxidant function of Eimeria tenella-infected broilers.

"Shi Ying Zi" powder is a traditional Chinese herbal formula for preventing and treating coccidiosis. In our previous studies, it showed anticoccidial effects and exhibited the potential to control Eimeria tenella infection. In this research, we evaluated the antioxidation and immune effect of "Shi Ying Zi" powder and its effective active ingredient osthole on coccidiosis-infected broilers to explore the mechanism of its anticoccidial effect. We analyzed changes in the antioxidant index, the pathological changes in cecum, immune index of serum and composition of cecal flora. The results showed that the use of "Shi Ying Zi" powder and osthole alleviated the pathological changes in the cecum, spleen and bursa of Fabricius, upregulated the spleen and bursal weigh index. "Shi Ying Zi" powder of 10 g/kg effectively rocovered the contents of interleukins and immunoglobulin in serum. Osthole increased the proportion of Firmicutes, Actino-bacteria and Lactobacillus in the cecum. In summary, "Shi Ying Zi" powder and osthole have anticoccidial effects, and they also can active the immunity, antioxidant functions and upregulate the beneficial bacteria population in Eimeria tenella-infected broilers.

Target Recognition in SAR Images by Deep Learning with Training Data Augmentation.

Mass production of high-quality synthetic SAR training imagery is essential for boosting the performance of deep-learning (DL)-based SAR automatic target recognition (ATR) algorithms in an open-world environment. To address this problem, we exploit both the widely used Moving and Stationary Target Acquisition and Recognition (MSTAR) SAR dataset and the Synthetic and Measured Paired Labeled Experiment (SAMPLE) dataset, which consists of selected samples from the MSTAR dataset and their computer-generated synthetic counterparts. A series of data augmentation experiments are carried out. First, the sparsity of the scattering centers of the targets is exploited for new target pose synthesis. Additionally, training data with various clutter backgrounds are synthesized via clutter transfer, so that the neural networks are better prepared to cope with background changes in the test samples. To effectively augment the synthetic SAR imagery in the SAMPLE dataset, a novel contrast-based data augmentation technique is proposed. To improve the robustness of neural networks against out-of-distribution (OOD) samples, the SAR images of ground military vehicles collected by the self-developed MiniSAR system are used as the training data for the adversarial outlier exposure procedure. Simulation results show that the proposed data augmentation methods are effective in improving both the target classification accuracy and the OOD detection performance. The purpose of this work is to establish the foundation for large-scale, open-field implementation of DL-based SAR-ATR systems, which is not only of great value in the sense of theoretical research, but is also potentially meaningful in the aspect of military application.

Effects of Solid Fermentation on Polygonatum cyrtonema Polysaccharides: Isolation, Characterization and Bioactivities.

Polygonati Rhizoma is a widely used traditional Chinese medicine (TCM) with complex pre-processing steps. Fermentation is a common method for processing TCM to reduce herb toxicity and enhance their properties and/or produce new effects. Here, in this study, using Bacillus subtilis and Saccharomyces cerevisiae, we aimed to evaluate the potential application of solid fermentation in isolating different functional polysaccharides from Polygonatum cyrtonema Hua. With hot water extraction, ethanol precipitation, DEAE anion exchange chromatography and gel filtration, multiple neutral and acidic polysaccharides were obtained, showing different yields, content, compositions and functional groups after fermentation. Combining in vitro experiments and in vivo aging and immunosuppressed mouse models, we further compared the antioxidant and immunomodulating bioactivities of these polysaccharides and found a prominent role of a natural polysaccharide (BNP) from fermented P. cyrtonema via Bacillus subtilis in regulating intestinal antioxidant defense and immune function, which may be a consequence of the ability of BNP to modulate the homeostasis of gut microbiota. Thus, this work provides evidence for the further development and utilization of P. cyrtonema with fermentation, and reveals the potential values of BNP in the treatment of intestinal disorders.

Hybrid FSK-PSK Waveform Optimization for Radar Based on Alternating Direction Method of Multiplier (ADMM).

In this paper, a new radar signal modulated with a hybrid of the frequency shift keying (FSK) and the phase shift keying (PSK) signal-i.e., the FSK-PSK signal-is studied. Different phase encoding sequences are used to modulate the sub-pulses to obtain lower sidelobe levels and ensure signal orthogonality. In addition, to counter intra-pulse slice repeater jamming of specific length generated by the enemy jammer, an orthogonal waveform made of sub-pulses of equal length based on the FSK-PSK modulation scheme is designed. The simulation results show that the optimized discrete phase encoding sequence can significantly enhance the orthogonality of the sub-pulse in the FSK-PSK signal and effectively suppress the slice repeater jamming. Two algorithms are proposed: (1) the low sidelobe waveform optimization algorithm based on ADMM (LSW-ADMM); and (2) the anti-slice-repeater-jamming algorithm based on ADMM (ASRJ-ADMM). Both algorithms exhibit fast convergence speed and low computational complexity.

Parameter Estimation for Interrupted Sampling Repeater Jamming Based on ADMM.

By repeatedly sampling, storing, and retransmitting parts of the radar signal, interrupted sampling repeater jamming (ISRJ) based on digital radio frequency memory (DRFM) can produce a train of secondary false targets symmetrical to the main false target, threatening to mislead or deceive the victim radar system. This paper proposes a computationally-effective method to estimating the parameters for ISRJ by resorting to the framework of alternating direction method of multipliers (ADMM). Firstly, the analytical form of pulse compression is derived. Then, for the purpose of estimating the parameters of ISRJ, the original problem is transformed into a nonlinear integer optimization model with respect to a window vector. On this basis, the ADMM is introduced to decompose the nonlinear integer optimization model into a series of sub-problems to estimate the width and number of ISRJ's sample slices. Finally, the numerical simulation results show that, compared with the traditional time-frequency (TF) method, the proposed method exhibits much better performance in accuracy and stability.

Tocilizumab and the risk of respiratory adverse events in patients with rheumatoid arthritis: a systematic review and meta-analysis of randomised controlled trials.

OBJECTIVES: The purpose of this study is to evaluate the relative risk (RR) of respiratory adverse events (AEs) among patients with RA treated with TCZ. METHODS: Databases (PubMed, Embase and Cochrane Library) were searched for randomised controlled trials (RCT) comparing the use of TCZ with placebo (PBO) or active comparator agents in adults with RA published until October 28, 2017. Statistical analyses were conducted to calculate the RR of infectious and non-infectious respiratory AEs and severe AEs (SAEs) using random-effects or fixed-effects models based on the heterogeneity of the included studies. RESULTS: Eight trials were ultimately included. TCZ was associated with an increased risk of infectious respiratory AEs relative to comparator agents (RR 1.53, 95% confidence interval [95% CI] 1.04-2.25) but was not associated with an increased risk of non-infectious respiratory AEs (RR 1.19, 95% CI 0.86-1.64). A subgroup analysis revealed similar results for non-infectious AEs and SAEs in the comparisons of TCZ with MTX and adalimumab (ADA), whereas increased risks of these AEs but not SAEs were observed compared with the PBO. CONCLUSIONS: Our meta-analysis did not reveal an increase in the risk of non-infectious respiratory AEs in adult patients with RA who were treated with TCZ compared with other csDMARDs and bDMARDs in RCTs.

Exogenous IL-33 Restores Dendritic Cell Activation and Maturation in Established Cancer.

The role of IL-33, particularly in tumor growth and tumor immunity, remains ill-defined. We show that exogenous IL-33 can induce robust antitumor effect through a CD8+ T cell-dependent mechanism. Systemic administration of rIL-33 alone was sufficient to inhibit growth of established tumors in transplant and de novo melanoma tumorigenesis models. Notably, in addition to a direct action on CD8+ T cell expansion and IFN-γ production, rIL-33 therapy activated myeloid dendritic cells (mDCs) in tumor-bearing mice, restored antitumor T cell activity, and increased Ag cross-presentation within the tumor microenvironment. Furthermore, combination therapy consisting of rIL-33 and agonistic anti-CD40 Abs demonstrated synergistic antitumor activity. Specifically, MyD88, an essential component of the IL-33 signaling pathway, was required for the IL-33-mediated increase in mDC number and upregulation in expression of costimulatory molecules. Importantly, we identified that the IL-33 receptor ST2, MyD88, and STAT1 cooperate to induce costimulatory molecule expression on mDCs in response to rIL-33. Thus, our study revealed a novel IL-33-ST2-MyD88-STAT1 axis that restores mDC activation and maturation in established cancer and, thereby, the magnitude of antitumor immune responses, suggesting a potential use of rIL-33 as a new immunotherapy option to treat established cancer.

Targeting Ornithine Decarboxylase by α-Difluoromethylornithine Inhibits Tumor Growth by Impairing Myeloid-Derived Suppressor Cells.

α-Difluoromethylornithine (DFMO) is currently used in chemopreventive regimens primarily for its conventional direct anticarcinogenesic activity. However, little is known about the effect of ornithine decarboxylase (ODC) inhibition by DFMO on antitumor immune responses. We showed in this study that pharmacologic blockade of ODC by DFMO inhibited tumor growth in intact immunocompetent mice, but abrogated in the immunodeficient Rag1(-/-) mice, suggesting that antitumor effect of DFMO is dependent on the induction of adaptive antitumor T cell immune responses. Depletion of CD8(+) T cells impeded the tumor-inhibiting advantage of DFMO. Moreover, DFMO treatment enhanced antitumor CD8(+) T cell infiltration and IFN-γ production and augmented the efficacy of adoptive T cell therapy. Importantly, DFMO impaired Gr1(+)CD11b(+) myeloid-derived suppressor cells (MDSCs) suppressive activity through at least two mechanisms, including reducing arginase expression and activity and inhibiting the CD39/CD73-mediated pathway. MDSCs were one primary cellular target of DFMO as indicated by both adoptive transfer and MDSC-depletion analyses. Our findings establish a new role of ODC inhibition by DFMO as a viable and effective immunological adjunct in effective cancer treatment, thereby adding to the growing list of chemoimmunotherapeutic applications of these agents.

[Recognition and use of Aconitum carmichaeli from the pre-Qin period to Tang Dynasty-Also on rules in evolution of traditional Chinese medicine].

The recognition and use of Aconitum carmichaeli have undergone various changes from the pre-Qin period to Tang dynasty. From "the drug of evil" to "the leader of hundreds of medicine ", people's understanding of A. carmichaeli is more and more deep and specific. The medicinal values of A. Carmichaeli have been excavated, and it is widely used in brewing skill, agricultural production, Taoism, Buddhism and festival customs. Its function is becoming more and more diversified and routinized. By studying it, we can glimpse some rules in the evolution of traditional Chinese medicine, for instance relationships between drugs and poisons, drugs and non-drug; the inheritance and integration of medical books' recording; the generalization and routinization of Chinese medicinal medicines' functions, and so on.

Malignancies in systemic rheumatic diseases: A mini review.

There is an increased risk of malignancies in patients with many systemic rheumatic diseases, which negatively impact on their quality of life. The risk and types of malignancies can differ by the type of rheumatic diseases. Possible mechanisms linking them are dynamic and complicated, including chronic inflammation and damage in rheumatic disease, inability to clear oncogenic infections, shared etiology and some anti-rheumatic therapies. Although certain disease-modifying anti-rheumatic drugs (DMARDs) have been proved to be potentially carcinogenic, the majority of them were not associated with increased risk of most malignancies in patients with systemic rheumatic diseases.

Reproductive Biology and Distribution of the Blue Shark (Prionace glauca) in the Western Indian Ocean.

Due to the limited biological research on the blue shark in the Indian Ocean, such as the lack of a clear understanding of its reproductive biology and distribution, our study analyzed and evaluated the fork length distribution, sexual maturity length, reproductive capacity, and spatiotemporal distribution of blue sharks based on biological data and capture location information collected in the western Indian Ocean from 2010 to 2020. The objective of this study is to provide reliable biological information important in performing future stock assessments vital for species conservation in this region. A total of 791 male (33-249.5 cm FL) and 803 female (12-349.6 cm FL) blue sharks were collected in the West Indian Ocean. We used the morphology of the sexual organs to ascertain their sexual maturity. Results show that the observed size at 50% sexual maturity of male blue sharks in the West Indian Ocean was 161.4cm FL (192.4 cm TL) for males and 179.3 cm FL (213.9 cm TL) for females based on logistic curve analysis. The average litter size of pregnant blue sharks was 33.7 pups. There were significant differences in the distribution of blue shark individuals with different sexual maturity levels in different quarters (p < 0.05). This study suggests that the area near the equator in the Indian Ocean from October to March of the following year may be the mating ground for blue sharks, while the temperate waters in the Indian Ocean are the nursery ground and parturition ground for pregnant and juvenile throughout the whole year. Therefore, it is recommended to adopt a more scientific and reasonable operational method in these areas.

Friend and foe: the regulation network of ascites components in ovarian cancer progression.

The tumor microenvironment (TME) and its complex role in cancer progression have been hotspots of cancer research in recent years. Ascites, which occurs frequently in patients with ovarian cancer especially in advanced stages, represents a unique TME. Malignant ascites contains abundant cellular and acellular components that play important roles in tumorigenesis, growth, metastasis, and chemoresistance of ovarian cancer through complex molecular mechanisms and signaling pathways. As a valuable liquid biopsy sample, ascites fluid is also of great significance for the prognostic analysis of ovarian cancer. The components of ovarian cancer ascites are generally considered to comprise tumor-promoting factors; however, in recent years studies have found that ascites also contains tumor-suppressing factors, raising new perspectives on interactions between ascites and tumors. Malignant ascites directly constitutes the ovarian cancer microenvironment, therefore, the study of its components will aid in the development of new therapeutic strategies. This article reviews the current research on tumor-promoting and tumor-suppressing factors and molecular mechanisms of their actions in ovarian cancer-derived ascites and therapeutic strategies targeting ascites, which may provide references for the development of novel therapeutic targets for ovarian cancer in the future.

Current status and outlook of minimally invasive treatment for leiomyomas.

OBJECTIVES: Leiomyomas are benign, highly prevalent gynecologic conditions that can cause abnormal uterine bleeding, pelvic pain, urinary difficulties, and/or bladder or rectal obstruction. With advances in medical technology, women are increasingly interested in treatments that avoid surgery and/or preserve the uterus, which has undoubtedly contributed to the development of minimally invasive approaches. This article reviews the literature and evaluates the effectiveness and safety of minimally invasive approaches for the treatment of leiomyomas and describes the current state of development of minimally invasive treatment modalities for leiomyomas. MATERIAL AND METHODS: Web of Science and PubMed were systematically evaluated using the following keywords: uterine artery embolization, high-intensity focused ultrasound, microwave ablation, radiofrequency ablation, myomectomy, hysterectomy, leiomyomas, fertility. English abstracts relevant to the topic were selected and full-text articles were carefully analyzed. RESULTS: Uterine artery embolization is an effective treatment modality that has been widely validated, and the remaining means each have their distinct advantages in clinical practice, but more practical and comparative studies are needed. Minimally invasive myomectomy and minimally invasive hysterectomy are technically advanced compared to classical open surgery and are widely used due to the completion of practical experience, but a continuous interest in non-invasive minimally invasive treatment modalities is retained. CONCLUSIONS: Minimally invasive treatment modalities for leiomyomas have emerged as an important treatment option when considering patient requirements, and further research and practice are needed to support their development into a mainstream modality for the treatment of leiomyomas.

Integrative analysis of prognostic factors in Chinese core binding factor leukemia.

The characteristics of core binding factor (CBF) leukemia appear to differ between Chinese and Caucasian patients. In this study, we analyzed the biological and clinical characteristics of 76 Chinese CBF leukemia patients out of 425 newly diagnosed acute myeloid leukemia (AML) patients. The frequency of CBF AML was 17.9%. Patients harboring t(8;21) were predominant in CBF AML. The incidence of c-kit mutation in CBF AML was 28.9%. The N822K mutation appeared to be more prevalent in Chinese CBF AML patients. Multivariate analysis showed that c-kit mutation and high white blood cell count could negatively impact overall survival (OS) (HR=2.74 and 6.24, P=0.007 and 0.022, respectively) but did not affect relapse-free survival (RFS). Kaplan-Meier analysis showed a significant difference in both OS and RFS between wild-type and mutated c-kit patients. Although we had included recently reported prognostic indicators in our analysis, our results demonstrated that only c-kit mutation and high white blood cell count had prognostic impact on Chinese CBF AML patients.

Association between B-group vitamins and venous thrombosis: systematic review and meta-analysis of epidemiological studies.

A homocysteine-independent role for B-group vitamins on venous thrombosis (VT) development has been reported. However, related research findings remain inconsistent. PUBMED, EMBASE, and COCHRANE databases were searched to collect information on all eligible studies to make a meta-analysis about the relationship between B-group vitamins and VT. Literature search results did not suggest a correlation between thiamin, pantothenic acid, niacin, or riboflavin with VT. Based on their correlations in the literature, folic acid, vitamin B12, B6 were considered in the meta-analysis and systematic review. Significant standardized mean differences were obtained for plasma folic acid (-0.55; 95% CI, -0.75 to -0.36) and vitamin B12 (-0.34; 95% CI, -0.55 to -0.13). Reduced levels of folic acid and vitamin B12 may be independent risk factors of VT. Moreover, a qualitative systematic review indicated that low level of vitamin B6 was an independent risk factor of VT. Randomized clinical studies of B-group vitamins supplementation showed varying results on VT prevention. Multivitamin supplementation for VT prevention, regardless of homocysteine level, would be of interest. Further prospective clinical studies are needed to provide additional evidence on the clinical benefits of B-group vitamin supplementation for VT.