Germanene saturable absorber for mode-locked operation in an all-fiber laser with multiple dispersion environments.

In this paper, a high-quality germanene-polyvinyl alcohol (PVA) saturable absorber (SA) with a modulation depth of 3.05% and a saturation intensity of 17.95M W/c m 2 was prepared. Stable conventional mode-locking and harmonic mode-locking (HML) were achieved in germanene-based Er-doped fiber lasers (EDFL) using dispersion management techniques. In a cavity with a net dispersion value of -0.22p s 2, the conventional soliton had a center wavelength of 1558.2 nm, a repetition frequency of 19.09 MHz, and a maximum 3 dB spectrum bandwidth of 3.5 nm. The highest repetition frequencies achieved in cavities with net dispersion values of -2.81p s 2, -1.73p s 2, and -1.09p s 2 were 9.48 MHz, 12.75 MHz, and 12.10 MHz for HML, respectively. Furthermore, the effects of dispersion, power, and the polarization state on HML were systematically investigated. Our research results fully demonstrate the capability of germanene as an optical modulator in generating conventional mode-locked and harmonic mode-locked solitons. This provides meaningful references for promoting its application in ultrafast fiber lasers.

Safety and efficacy of bilateral superselective adrenal arterial embolization for treatment of idiopathic hyperaldosteronism: a prospective single-center study.

OBJECTIVE: This study aimed to assess the efficacy and safety of bilateral superselective adrenal arterial embolization (SAAE) in patients with bilateral idiopathic hyperaldosteronism (IHA), a subtype of PA. METHODS: Ninety-eight patients with bilateral IHA underwent bilateral SAAE between August 2022 and August 2023. Sixty-eight patients were followed up for up to 12 months. The study outcomes were evaluated using the criteria provided by the Primary Aldosteronism Surgical Outcome (PASO) guidelines. RESULTS: The mean reductions in systolic and diastolic blood pressure were 27.4 ± 21.3 mmHg and 23.1 ± 17.4 mmHg, respectively (p < 0.001). The rates of clinical success and biochemical success after adrenal artery ablation were 63.2% (43/68) and 39.7% (27/68), respectively. Overall, there were significant reductions in daily defined doses (DDD), aldosterone/renin ratio (ARR), and plasma aldosterone levels (p < 0.001). Plasma renin levels increased by a mean value of 10.4 ± 39.0 pg/mL (p = 0.049), and potassium levels increased by 0.40 ± 0.63 mmol/L (p < 0.001). No significant adverse events were reported during SAAE or the follow-up period of up to one year. Additionally, no abnormalities were detected by adrenal 68Ga-Pentixafor PET/CT scans before or after SAAE. CONCLUSION: Bilateral SAAE appears to lead to sustained improvements in blood pressure and biochemical parameters in patients with bilateral PA, with minimal adverse effects. This suggests that bilateral SAAE could serve as an effective alternative approach for treating bilateral IHA, potentially curing this condition.

ncRNA-Encoded Peptides or Proteins and Cancer.

Non-coding RNAs (ncRNAs) are unique RNA transcripts that have been widely identified in the eukaryotic genome and have been shown to play key roles in the development of many cancers. However, the rapid development of genome-wide translation profiling and ribosome profiling has revealed that a small number of small open reading frames (sORFs) within ncRNAs actually have peptide- or protein-coding potential. The peptides or proteins encoded by ncRNA (HOXB-AS3, encoded by long ncRNA [lncRNA]; FBXW7-185aa, PINT-87aa, and SHPRH-146aa, encoded by circular RNA [circRNA]; and miPEP-200a and miPEP-200b, encoded by primary miRNAs) have been shown to be critical players in cancer development and progression, through effects upon the regulation of glucose metabolism, the epithelial-to-mesenchymal transition, and the ubiquitination pathway. In this review, we summarize the reported peptides or proteins encoded by ncRNAs in cancer and explore the application of these peptides or proteins in the development of anti-tumor drugs and the identification of relevant therapeutic targets and tumor biomarkers.

[Multicenter analysis of risk factors and clinical characteristics of shoulder dystocia].

OBJECTIVE: To explore the risk factors and clinical characteristics of shoulder dystocia. METHODS: The data of 44 580 single pregnancy and full-term head delivery were colleceted in the Third Affiliated Hospital of Guangzhou Medical University, Nanfang Hospital, Shenzhen Nanshan Hospital, Peking University Shenzhen Hospital and Yue Bei People's Hospital from January 2008 to September 2013. Totally 116 cases of shoulder dystocia were defined as the shoulder dystocia group, and the others were in the control group. The clinical data of the two groups were analyzed retrospectively, including the maternal age, maternal height, pre-gestational body mass index, weight gain during pregnancy, gestational weeks, gravidity, parity, fundal height, fetal abdominal perimeter, shoulder dystocia medical history, macrosomia, gestational diabetes mellitus, pre-gestational diabetes mellitus, post-term pregnancy and the condition of labor stages. RESULTS: (1) The incidence of shoulder dystocia was 0.260% (116/44 580). The maternal age, pre-gestational body mass index and weight gain during pregnancy in the shoulder dystocia group were higher than those in the control group (all P < 0.01). While the maternal height, gestational weeks, gravidity, parity, fundal height, abdominal circumference in the two groups had no significant difference (all P > 0.05). (2) In the shoulder dystocia group, the incidence of shoulder dystocia medical history (11.21%, 13/116), macrosomia (13.79% , 16/116), pre-gestational diabetes mellitus (7.76% , 9/116), post-term pregnancy (10.34%, 12/116), prolongation of maximum acceleration phase (8.62%, 10/116) and prolongation of second labor stage (7.76%, 9/116) were different from those in the control group[1.43% ( 636/44 464), 1.48% (658/ 44 464), 0.57% ( 252/44 464), 1.15% (513/44 464),0.72% (322/44 464), 0.65% (289/44 464), respectively; all P < 0.05]. (3) Logistic regression analysis showed that the risk factors of shoulder dystocia were maternal age over thirty-five years (OR = 1.116, 95%CI: 1.022-2.445), pre-gestational body mass index more than 27 kg/m(2) (OR = 1.893, 95% CI: 1.358-2.228), weight gain more than 20 kg during pregnancy (OR = 2.031, 95% CI: 1.749-3.231), shoulder dystocia medical history (OR = 2.138, 95%CI:1.564-3.853), macrosomia (OR = 3.276, 95% CI:2.315- 4.638), pre-gestational diabetes mellitus (OR = 3.261, 95% CI:2.237- 4.943), post-term pregnancy (OR = 1.473, 95% CI:1.003-2.721), prolongation of the maximum acceleration phase (OR = 2.022, 95% CI:1.681- 3.732), prolongation of second labor stage(OR = 1.943, 95% CI:1.285- 3.215). CONCLUSION: Maternal age over thirty-five years old, pre-gestational body mass index more than 27 kg/m(2), weight gain more than 20 kg during pregnancy, shoulder dystocia medical history, macrosomia, pre-gestational diabetes mellitus, post-term pregnancy, prolongation of the maximum acceleration phase, and prolongation of second labor stage are risk factors and clinical characteristics of shoulder dystocia.

Some remarks on the argument appealing to nature against synthetic biology.

This paper will focus on analyzing the argument with appealing to nature against synthetic biology and provide a counter-argument against it through demonstrating the ambiguity of the concept of nature, denying the existence of a morally significant line between natural and non/unnatural, and disproving the allegations against synthetic biology raised by the argument appealing to nature. The paper consists of two parts following a brief introduction. The first part will describe the argument appealing to nature against synthetic biology, and identify the deficiencies of the argument per se, e.g., the ambiguity of the concept 'nature'; and the problems in the morally significant line between the natural and the non/unnatural. The second part will discuss the allegations to synthetic biology stemming from this argument, e.g., committing metaphysical and ethical mistakes, and doing possible harms to the environment.

Redirecting Tumor Evolution with Nanocompiler Precision for Enhanced Therapeutic Outcomes.

Precisely programming the highly plastic tumor expression profile to render it devoid of drug resistance and metastatic potential presents immense challenges. Here, a transformative nanocompiler designed to reprogram and stabilize the mutable state of tumor cells is introduced. This nanocompiler features a trio of components: 2-deoxy-d-glucose-modified lipid nanoparticles to inhibit glucose uptake, iron oxide nanoparticles to induce oxidative stress, and a deubiquitinase inhibitor to block adaptive protein profile changes in tumor cells. By specifically targeting the hypermetabolic nature of tumors, this approach disrupted their energy production, ultimately fostering a state of vulnerability and impeding their ability to adapt and resist. The results of this study indicate a substantial reduction in tumor growth and metastasis, thus demonstrating the potential of this strategy to manipulate tumor protein expression and fate. This proactive nanocompiler approach promises to steer cancer therapy toward more effective and lasting outcomes.

A Tetrahedral Framework DNA-Based Bioswitchable miR-150 Delivery System for Sepsis.

Sepsis is a disease with high morbidity and mortality, for which effective treatments are lacking. In recent years, microRNAs (miRs) have been shown to regulate numerous biological processes and can function as therapeutic options for various diseases. However, the poor stability and cell entry properties of miRs have greatly limited their clinical application. In this study, we developed a tetrahedral framework nucleic acid (tFNA)-based bioswitchable miR delivery system (BiRDS) to deliver miR-150 for the treatment of sepsis. BiRDS showed anti-inflammatory effects both in vitro and in vivo by regulating the NF-κB and Notch1 pathways. Therefore, this system holds promise as an ideal candidate for tackling systemic inflammation and multiorgan dysfunction in septic patients in the future.

A bioswitchable siRNA delivery system: RNAi therapy based on tetrahedral framework nucleic acids for bone defect repair.

Craniofacial bone defects, caused by trauma, congenital abnormalities, or various diseases, present a significant challenge in regenerative medicine. One approach to addressing this problem is the use of RNA interference (RNAi) technology with small interfering RNA (siRNA). CKIP-1 is a negative regulatory molecule for bone formation. However, direct applications of CKIP-1 siRNA for bone defects are still limited. The instability and poor cellular uptake ability of CKIP-1 siRNA restrict its clinical applications. A new drug delivery system is critically needed to enhance the effectiveness and potential applications of CKIP-1 siRNA. Tetrahedral framework nucleic acid (tFNA) is a promising drug delivery system due to its stability and transport abilities. In this study, we developed a bioswitchable siRNA delivery system (BiRDS) based on tFNA to carry CKIP-1 siRNA and examined its effect on bone defect repair. siRNA was successfully loaded into the tFNA core, forming BiRDS, which improved siRNA stability and cellular uptake. After entering cells, BiRDS exposed siRNA, enhancing CKIP-1 silencing efficiency. This system significantly promoted osteogenic differentiation and bone regeneration in rat mandibular bone defects, offering a new strategy for bone regeneration therapy.

17ß-Estradiol, through activating the G protein-coupled estrogen receptor, exacerbates the complication of benign prostatic hyperplasia in type 2 diabetes mellitus patients by inducing prostate proliferation.

Benign prostatic hyperplasia (BPH) is one of the major chronic complications of type 2 diabetes mellitus (T2DM), and sex steroid hormones are common risk factors for the occurrence of T2DM and BPH. The profiles of sex steroid hormones are simultaneously quantified by LC-MS/MS in the clinical serum of patients, including simple BPH patients, newly diagnosed T2DM patients, T2DM complicated with BPH patients and matched healthy individuals. The G protein-coupled estrogen receptor (GPER) inhibitor G15, GPER knockdown lentivirus, the YAP1 inhibitor verteporfin, YAP1 knockdown/overexpression lentivirus, targeted metabolomics analysis, and Co-IP assays are used to investigate the molecular mechanisms of the disrupted sex steroid hormones homeostasis in the pathological process of T2DM complicated with BPH. The homeostasis of sex steroid hormone is disrupted in the serum of patients, accompanying with the proliferated prostatic epithelial cells (PECs). The sex steroid hormone metabolic profiles of T2DM patients complicated with BPH have the greatest degrees of separation from those of healthy individuals. Elevated 17ß-estradiol (E2) is the key contributor to the disrupted sex steroid hormone homeostasis, and is significantly positively related to the clinical characteristics of T2DM patients complicated with BPH. Activating GPER by E2 via Hippo-YAP1 signaling exacerbates high glucose (HG)-induced PECs proliferation through the formation of the YAP1-TEAD4 heterodimer. Knockdown or inhibition of GPER-mediated Hippo-YAP1 signaling suppresses PECs proliferation in HG and E2 co-treated BPH-1 cells. The anti-proliferative effects of verteporfin, an inhibitor of YAP1, are blocked by YAP1 overexpression in HG and E2 co-treated BPH-1 cells. Inactivating E2/GPER/Hippo/YAP1 signaling may be effective at delaying the progression of T2DM complicated with BPH by inhibiting PECs proliferation.

Bilateral superselective adrenal artery embolization for bilateral primary aldosteronism: a novel approach in an efficacy and safety proof-of-principle trial.

Superselective adrenal artery embolization (SAAE) offers a novel approach for treating primary aldosteronism (PA). In this study, we aimed to assess the efficacy and safety of SAAE for the treatment of PA based on the lateralization results obtained from adrenal vein sampling (AVS).In this prospective study, we enrolled 40 patients with PA who underwent SAAE. The patients were categorized into two groups, unilateral PA and bilateral PA, based on AVS results. Clinical parameters and biochemical markers were assessed at 3 and 12 months postoperatively. The primary outcomes were changes in blood pressure and defined daily dose (DDD) of antihypertensive medications compared to baseline. Thirty-eight patients achieved technical success, with favorable clinical and biochemical efficacy rates. At three months postoperatively, the clinical efficacy rates were 79.2% and 78.6% for the UPA and BPA groups, respectively. At 12 months, the rates were 83.3% and 71.4%, respectively. Both groups exhibited a significant decrease in average blood pressure at 3 and 12 months compared with baseline (P < 0.001), and there was also a notable reduction in DDD (P < 0.05). At three months, the biochemical efficacy rates were 61.9% and 58.3% in the UPA and BPA groups, respectively. Due to loss to follow-up, biochemical indicators were not assessed at 12 months postoperatively. No severe adverse reactions occurred during or after SAAE. Patients with both UPA and BPA can benefit from SAAE. The superiority of bilateral adrenal artery embolization in the treatment of BPA over unilateral adrenal artery embolization requires further investigation.

TARDBP promotes ovarian cancer progression by altering vascular endothelial growth factor splicing.

Disruptions in alternative splicing regulation play an essential role in ovarian cancer progression. However, the underlying mechanism remains unclear. TAR DNA-binding protein (TARDBP) plays a crucial role in alternative splicing regulation. Herein we found that TARDBP expression was significantly upregulated in OC tissue samples, particularly in cases of metastasis; further, TARDBP expression was markedly upregulated in OC patients with poor prognosis. These findings were validated by extensive tissue microarray data. TARDBP was also found to promote tumorigenesis and metastasis of OC cells in vitro and in vivo. Mechanistically, TARDBP increased the binding of the splicing factor serine/arginine-rich splicing factor 1 (SRSF1) to intron 7 of vascular endothelial growth factor (VEGF), increasing the formation of the proangiogenic VEGF165 isoform and decreasing that of the antiangiogenic VEGF165b isoform. The abnormal alternative splicing event was responsible for the activation of angiogenesis and contributed to the progression of OC. To conclude, TARDBP was found to regulate the alternative splicing of VEGF via SRSF1, induce the formation of VEGF165 but inhibit that of VEGF165b, and promote OC angiogenesis. Hence, TARDBP can serve as an independent prognostic factor and new target for OC cancer therapy.

Novel hydrophilic straw biochar for the adsorption of neonicotinoids: kinetics, thermodynamics, influencing factors, and reuse performance.

Nitenpyram (NIT) is the most water-soluble neonicotinoid (NEO). It has been shown to pose a serious threat to human health and the environment but was always ignored due to its limited market share. There were few experts who studied NIT's transport behavior on biochar. In this study, two types of biochar were co-activated separately using zinc chloride combined with phosphoric acid and potassium hydroxide combined with acetic acid, marked as ZBC and KBC. Characterizations suggested that hydrophilic ZBC and KBC had more surface functional groups than unmodified biochar (BC), and specific surface areas of ZBC (456.406 m2·g-1) and KBC (750.588 m2·g-1) were significantly higher than of BC (67.181 m2·g-1). The pore structures of KBC and ZBC were hierarchical porous structures with different pore sizes and typical microporous structure, respectively. The adsorption performance of either NIT or IMI on KBC was better than that on ZBC. Only 0.4 g·L-1 of KBC can absorb 89.62% of NIT in just 5 min. The equilibrium adsorption amounts of NIT on ZBC and KBC were 17.995 mg·g-1 and 82.910 mg·g-1. Elovich and Langmuir models were used to evaluate the whole adsorption process, which was attributed to the chemisorption mechanism. In addition, removal rates of NIT were negatively correlated to NIT's initial concentration and positively correlated to the dose of biochar. pH had almost no effect on adsorption, but the presence of salt ions can inhibit the removal of NIT. Long-term stabilities of biochars were also acceptable. These findings will promote the development in the preparation of biochar fields and provide a positive reference value for NEO removal.

Flexible and hierarchical metal-organic framework composite as solid-phase media for facile affinity-tip fabrication to selectively enrich glycopeptides and phosphopeptides.

Micro-tip-based solid-phase microextraction is considered as one of the green and powerful analytical sample preparation techniques, but its efficiency is severely hampered by some basic issues such as tedious fabrication, instability of sorbent bed, and blocking of the tip, especially for biological samples due to low permeability. These issues are tackled by introducing a flexible and hierarchical substrate in the microtip, having good mechanical strength and specific functionality to capture the desired biomolecules. Considering the well-ordered and flexible structure of melamine foam, it was used as a substrate and for hydrophilic interaction chromatography (HILIC). Metal-organic framework, due to its excellent characteristics, was grafted on its surface anchored by self-assembling polydopamine. The resulting material was characterized and packed in the tip by just pressing the material in the conical structure of the tip. This affinity tip established good and tunable permeability and was used to selectively enrich glycopeptides as well as phosphopeptides. The affinity tip demonstrated excellent performance to enrich glycopeptides and phosphopeptides with a low limit of detection up to 0.5 fmol µL-1 from tryptic digests of horseradish peroxidase and ß-Casein, respectively, and was stable up to 5 rounds of enrichment. Moreover, this affinity-tip also exhibited high selectivity up to up to 1:1000 (HRP digest to BSA digest) for glycopeptides and 1:200 (ß-Casein digest to BSA digest) for phosphopeptides and demonstrated several other fascinating characteristics such as; excellent size exclusion effect for the omission of large-sized proteins, modest backpressure, reproducibility, reusability, smooth enrichment, and successfully applied to a human saliva sample.

The Design of Near-Perfect Spectrum-Selective Mirror Based on Photonic Structures for Passive Cooling of Silicon Solar Cells.

When exposed to sunlight, crystalline silicon solar cells (CSSC) will not only generate electric energy but are also heated by solar radiation. Such a self-heating effect makes the working temperature of CSSC 20-40 °C higher than that of the ambient temperature, which degrades their efficiency and reliability. The elevated operating temperatures of CSSC are mainly derived from absorbing photons that cannot be converted to electrons. Therefore, it is important to prevent CSSC from absorbing useless solar light to have a better cooling effect. In this paper, photonic structures based spectrum-selective mirror is designed to cool the operating temperatures of CSSC passively. The mirror could make CSSC absorb about 93% of the sunlight in the wavelength range of 0.3 to 1.1 µm and only absorb about 4% of the sunlight in the wavelength range of 1.1 to 2.5 µm. Meanwhile, the design has good compatibility with the radiative cooling strategy. By applying selective-absorptive and radiative cooling strategies, the operating temperature of CSSC could be decreased about 23.2 K and 68.1 K under different meteorological conditions. Moreover, unlike the single radiative cooling strategy, the spectrum-selective mirror also has effective cooling effects in high wind speed meteorological conditions.

Small Protein Hidden in lncRNA LOC90024 Promotes "Cancerous" RNA Splicing and Tumorigenesis.

Conventional therapies for late-stage colorectal cancer (CRC) have limited effects because of chemoresistance, recurrence, and metastasis. The "hidden" proteins/peptides encoded by long noncoding RNAs (lncRNAs) may be a novel resource bank for therapeutic options for patients with cancer. Here, lncRNA LOC90024 is discovered to encode a small 130-amino acid protein that interacts with several splicing regulators, such as serine- and arginine-rich splicing factor 3 (SRSF3), to regulate mRNA splicing, and the protein thus is named "Splicing Regulatory Small Protein" (SRSP). SRSP, but not LOC90024 lncRNA itself, promotes CRC tumorigenesis and progression, while silencing of SRSP suppresses CRC tumorigenesis. Mechanistically, SRSP increases the binding of SRSF3 to exon 3 of transcription factor Sp4, resulting in the inclusion of Sp4 exon 3 to induce the formation of the "cancerous" long Sp4 isoform (L-Sp4 protein) and inhibit the formation of the "noncancerous" short Sp4 isoform (S-Sp4 peptide), which lacks the transactivation domain. The upregulated SRSP level is positively associated with malignant phenotypes and poor prognosis in patients with CRC. Collectively, the findings uncover that a lncRNA-encoded small protein SRSP induces "cancerous" Sp4 splicing variant formation and may be a potential prognostic biomarker and therapeutic target for patients with CRC.

An oncopeptide regulates m6A recognition by the m6A reader IGF2BP1 and tumorigenesis.

N6-methyladenosine (m6A) is the most prevalent modification in eukaryotic RNAs. The biological importance of m6A relies on m6A readers, which control mRNA fate and function. However, it remains unexplored whether additional regulatory subunits of m6A readers are involved in the m6A recognition on RNAs. Here we discover that the long noncoding RNA (lncRNA) LINC00266-1 encodes a 71-amino acid peptide. The peptide mainly interacts with the RNA-binding proteins, including the m6A reader IGF2BP1, and is thus named "RNA-binding regulatory peptide" (RBRP). RBRP binds to IGF2BP1 and strengthens m6A recognition by IGF2BP1 on RNAs, such as c-Myc mRNA, to increase the mRNA stability and expression of c-Myc, thereby promoting tumorigenesis. Cancer patients with RBRPhigh have a poor prognosis. Thus, the oncopeptide RBRP encoded by LINC00266-1 is a regulatory subunit of m6A readers and strengthens m6A recognition on the target RNAs by the m6A reader to exert its oncogenic functions.

TBC1D8 Amplification Drives Tumorigenesis through Metabolism Reprogramming in Ovarian Cancer.

Cancer cells undergo metabolic reprogramming to support their energy demand and biomass synthesis. However, the mechanisms driving cancer metabolism reprogramming are not well understood. Methods: The differential proteins and interacted proteins were identified by proteomics. Western blot, qRT-PCR and IHC staining were used to analyze TBC1D8 levels. In vivo tumorigenesis and metastasis were performed by xenograft tumor model. Cross-Linking assays were designed to analyze PKM2 polymerization. Lactate production, glucose uptake and PK activity were determined. Results: We established two aggressive ovarian cancer (OVCA) cell models with increased aerobic glycolysis. TBC1D8, a member of the TBC domain protein family, was significantly up-regulated in the more aggressive OVCA cells. TBC1D8 is amplified and up-regulated in OVCA tissues. OVCA patients with high TBC1D8 levels have poorer prognoses. TBC1D8 promotes OVCA tumorigenesis and aerobic glycolysis in a GAP activity-independent manner in vitro and in vivo. TBC1D8 bound to PKM2, not PKM1, via its Rab-GAP TBC domain. Mechanistically, TBC1D8 binds to PKM2 and hinders PKM2 tetramerization to decreases pyruvate kinase activity and promote aerobic glycolysis, and to promote the nuclear translocation of PKM2, which induces the expression of genes which are involved in glucose metabolism and cell cycle. Conclusions:TBC1D8 drives OVCA tumorigenesis and metabolic reprogramming, and TBC1D8 serves as an independent prognosis factor for OVCA patients.

Peptides/Proteins Encoded by Non-coding RNA: A Novel Resource Bank for Drug Targets and Biomarkers.

Non-coding RNAs (ncRNAs) are defined as RNA molecules that do not encode proteins, but recent evidence has proven that peptides/proteins encoded by ncRNAs do indeed exist and usually contain less than 100 amino acids. These peptides/proteins play an important role in regulating tumor energy metabolism, epithelial to mesenchymal transition of cancer cells, the stability of the c-Myc oncoprotein, and the ubiquitination and degradation of proliferating cell nuclear antigen (PCNA). These peptides/proteins represent promising drug targets for fighting against tumor growth or biomarkers for predicting the prognosis of cancer patients. In this review, we summarize the characteristics of peptides/proteins that have recently been identified as putative ncRNA translation products and their outlook for small molecule peptide drugs, drug targets, and biomarkers.

ECD promotes gastric cancer metastasis by blocking E3 ligase ZFP91-mediated hnRNP F ubiquitination and degradation.

The human ortholog of the Drosophila ecdysoneless gene (ECD) is required for embryonic development and cell-cycle progression; however, its role in cancer progression and metastasis remains unclear. Here, we found that ECD is frequently overexpressed in gastric cancer (GC), especially in metastatic GC, and is correlated with poor clinical outcomes in GC patients. Silencing ECD inhibited GC migration and invasion in vitro and metastasis in vivo, while ECD overexpression promoted GC migration and invasion. ECD promoted GC invasion and metastasis by protecting hnRNP F from ubiquitination and degradation. We identified ZFP91 as the E3 ubiquitin ligase that is responsible for hnRNP F ubiquitination at Lys 185 and proteasomal degradation. ECD competitively bound to hnRNP F via the N-terminal STG1 domain (13-383aa), preventing hnRNP F from interacting with ZFP91, thus preventing ZFP91-mediated hnRNP F ubiquitination and proteasomal degradation. Collectively, our findings indicate that ECD promotes cancer invasion and metastasis by preventing E3 ligase ZFP91-mediated hnRNP F ubiquitination and degradation, suggesting that ECD may be a marker for poor prognosis and a potential therapeutic target for GC patients.

Management of patients with placenta accreta in association with fever following vaginal delivery.

This study aims to analyze the clinical characteristics and to manage patients with retained placenta left in situ accompanied by fever following vaginal delivery.Twenty-one patients with retained placenta in association with fever following vaginal delivery were enrolled and managed at the maternity department of our university hospital between 2012 and 2014.All patients had risk factors for development of placenta accreta: previous cesarean sections (4/21), previous curettage (15/21), or uterine malformations (7/21). Placenta accreta was diagnosed following vaginal delivery in all patients, and manual removal of the placenta was attempted in 20 of 21 patients. The placenta left in situ was partial in 19 patients and was complete in 2 patients. All patients were managed with a multidisciplinary approach. Mifepristone was administrated to 16 patients. Fourteen patients received uterine artery embolization. Eleven patients were treated with ultrasound-guided curettage within 24 hours following delivery. Seven patients needed delayed-hysterectomy due to development of complications.Intrauterine operations during labor are not recommended if placenta accreta occurs in the fundus and/or in the cornual region of the uterus. Antibiotic treatment, interventional therapy, and ultrasound-guided curettage within 24 hours following vaginal delivery are the recommended conservative management strategies.