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Background: Insulin resistance (IR) is linked to an increased risk of neurological impairment following a stroke and may contribute to poor neurological prognosis in affected patients. The metabolic score for the insulin resistance index, shortened as the METS-IR, generally serves as a surrogate index for IR. However, its association with the severity of neurological impairment in patients with severe cerebral infarction (CI) in neurological intensive care units (ICU) has not been fully established. Methods: Patients with a diagnosis of CI, admitted to the neurological ICUs of Yangzhou University's Affiliated Hospital and Xuzhou Medical University's Affiliated Hospital, were included in the study. A multivariate logistic regression model and restricted cubic splines (RCS) were employed to explore the relationship between the METS-IR index and the severity of neurological impairment in these patients. The predictive capabilities of the METS-IR index and the triglyceride-glucose (TyG) index for outcome measures were compared through the ROC curve. Furthermore, a decision curve analysis was executed, and the integrated discrimination improvement (IDI) index was computed to evaluate the enhancements in predictive performance and clinical utility of various scoring systems with the inclusion of the METS-IR index. Subgroup analysis was conducted regarding age, BMI, and smoking status. Results: The study ultimately included 504 participants. Adjusted logistic regression and RCS results showed that as the METS-IR index increases, the risk of neurological impairment in patients with severe CI consistently grows (P for overall = 0.0146, P -nonlinear: 0.0689). The METS-IR index's predictive capability for neurological impairment (AUC = 0.669) was superior to that of the TyG index (AUC = 0.519). Conclusion: From the study results, the METS-IR index can serve as an important predictor for neurological impairment in ICU patients with severe CI. It can aid in the identification and early intervention of neurological impairment in these patients. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder and metabolic abnormality disease that mainly affects women of reproductive age. LINC00173, a novel long noncoding RNA (lncRNA), has emerged as an important factor in the development of PCOS. However, the role of LINC00173 in PCOS development and its specific upstream and downstream mechanisms remain to be further clarified. Here, we found that LINC00173 was significantly upregulated in granulosa cells (GCs) of PCOS patients, and played a crucial role in promoting apoptosis of GCs. Mechanistically, we observed the activation of endoplasmic reticulum (ER) stress in the GCs of PCOS patients, and the ER stress sensor ATF4 could directly induce LINC00173 expression by binding to its promoter. LINC00173 further upregulated the expression of Harakiri (HRK) and subsequently inhibited downstream PI3K/AKT pathway. In conclusions, our study uncovered that ER stress-induced upregulation of LINC00173 leads to increased HRK expression and inhibition of the PI3K/AKT pathway, thereby promoting the progression of PCOS. These findings provide a new therapeutic strategy for the treatment of PCOS. [ABSTRACT FROM AUTHOR]

This paper presents a non‐isolated DC‐DC converter designed to validate ultra‐high voltage gain using a modified double boost mode. The objective is to achieve exceptionally high voltage gain by integrating a modified triple boost technique (MTBT), interleaved with second main and auxiliary third MOSFETs, and a modified switched inductor‐capacitor (MSLC), effectively doubling the voltage transfer gain. Furthermore, MSLC is combined with the auxiliary third and double main MOSFET to double the voltage gain while concurrently mitigating voltage stress on the auxiliary MOSFET and diodes in the proposed converter (the PC). Additionally, all diodes in the MTBT operate under zero current switching (ZCS) and the double main and auxiliary third MOSFET face very low current stress at ultra‐high voltage gain. The input current of the PC remains steady without pulsating at a low duty ratio, making the PC more suitable for renewable energy systems. The PC offers numerous advantages, exhibiting high efficiency and ensuring minimal voltage stress on power devices with low current stress on the power switches. Notably, PC aims to elevate input voltages from 30 V to a variable output range of 335 to 600 V, delivering 440 watts at 96.1% efficiency. [ABSTRACT FROM AUTHOR]

Break-induced replication (BIR) is mutagenic, and thus its use requires tight regulation, yet the underlying mechanisms remain elusive. Here we uncover an important role of 53BP1 in suppressing BIR after end resection at double strand breaks (DSBs), distinct from its end protection activity, providing insight into the mechanisms governing BIR regulation and DSB repair pathway selection. We demonstrate that loss of 53BP1 induces BIR-like hyperrecombination, in a manner dependent on Polα-primase-mediated end fill-in DNA synthesis on single-stranded DNA (ssDNA) overhangs at DSBs, leading to PCNA ubiquitination and PIF1 recruitment to activate BIR. On broken replication forks, where BIR is required for repairing single-ended DSBs (seDSBs), SMARCAD1 displaces 53BP1 to facilitate the localization of ubiquitinated PCNA and PIF1 to DSBs for BIR activation. Hyper BIR associated with 53BP1 deficiency manifests template switching and large deletions, underscoring another aspect of 53BP1 in suppressing genome instability. The synthetic lethal interaction between the 53BP1 and BIR pathways provides opportunities for targeted cancer treatment. Break-induced replication (BIR) mechanism is mutagenic, and thus needs to be tightly regulated. Here the authors identify an important role of 53BP1 in suppressing mutagenic BIR, providing insights into DSB repair pathway selection and BIR regulation. [ABSTRACT FROM AUTHOR]

A multi-port DC–DC–AC converter system is analyzed in this paper, which is composed of a bidirectional CLLC resonant converter and a four-switch buck-boost (FSBB) converter by sharing one bridge arm, and then has a full-bridge inverter circuit connected in series. This multi-port DC–DC–AC system can work in some dual-port operation modes and three-port operation modes according to the actual requirements. Integrating the advantages of CLLC resonant converter and FSBB converter, the converter system has excellent soft switching characteristics and wide range voltage regulation capability. This multi-port DC–DC–AC system overcomes the limitation in the general dual-port bidirectional converter and reduces the structural complexity in the traditional three-port converter, which can meet the requirements of multi-port voltage applications in some cases. In this paper, the structure and operation mode of this converter system are described, and then appropriate control method for this converter system is selected. An experimental platform of the multi-port DC–DC–AC system is established, and those experimental results verify the validity and rationality of this converter system with its control method. [ABSTRACT FROM AUTHOR]

Objective: Endometrial cancer is stepping into the era of precision therapy. Genomic test is recommended for newly diagnostic patients. However, outpatients displayed more complex characteristics. Here, we elucidated the clinical characteristics and genomic profiling of outpatients with endometrial cancer at our institution. Methods: Between 2018 and 2023, 68 endometrial cancer received genomic tests at outpatient department of Fudan University Shanghai Cancer Center. Data, including age, pathological histology, FIGO stage and treatment strategy were collected. Germline mutations, molecular subtypes and other somatic mutations were also summarized. Results: Overall, 72.1% (49/68) of patients receive genomic tests at primary diagnosis, while 27.9% (19/68) of patients received tests at recurrence. Nine patients had deleterious germline mutations, including BRCA1(2), MLH1(1), MSH2(2, including one with co-mutation of RAD50), MSH6(2), FANCA(1), MUTYH(1). Molecular subtypes were recognized among 62 patients, as POLE super-mutation(4, 6.5%), MSI-H(7, 11.3%), CN-Low(36, 58.1%) and CN-High(15, 24.2%). Ten patients received anti-PD1 monotherapy or in combination with chemotherapy or anti-angiogenic therapy, with the duration of disease control of 1 to 35 months. The ORR rate was 30%, and six patients had stable disease. The median (range) follow-up time was 18(2–160) months. 23(33.8%) relapses were recorded, and CN-High subtype displayed worst PFS compared with other subtypes (P < 0.01). 6 deaths were reported including 2(5.6%) of CN-Low and 4(26.7%) of CN-High. Conclusion: Outpatients department gathered a considerable proportion of recurrent patients with complex genomic features. Patients with worse prognosis could be well studied, and anti-PD1 therapy was a promising salvage therapy in the real world. [ABSTRACT FROM AUTHOR]

Objective: To retrospectively explore the clinical significance of radiotherapy to the distant metastatic lymph nodes (cervical/ clavicular/ mediastinal et al.) in metastatic cervical cancer. Hereinto, these cervicothoracic lymph nodes were metastasized from IB1-IVA (initial stage at first treatment), and IVB initially had metastatic disease in these areas at diagnosis. Methods: Metastatic cervical cancer only with the distant cervicothoracic metastatic lymph nodes (cervical/ clavicular/ mediastinal et al.), without distant parenchymal organs metastasis such as lung, liver, bone, and peritoneum, were enrolled in the analysis. These patients were classified into IB1-IVA and IVB based on their initial stage of first treatment. All patients received IMRT for the distant metastatic lymph nodes. The progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan–Meier method. Results: Overall, the median PFS was 9 months, and the median OS was 27 months. The subgroup analysis showed that for IB1-IVA, the median PFS was 11 months, and the median OS was 30.5 months. For IVB, the median PFS was 8 months, and the median OS was 16 months. Conclusion: Radiotherapy is beneficial to the distant metastatic lymph nodes (cervical/ clavicular/ mediastinal et al.), and could effectively bring the longer PFS and OS for metastatic cervical cancer. [ABSTRACT FROM AUTHOR]

Pyroptosis may play an important role in the resistance of ovarian cancer (OC) to chemotherapy. However, the mechanism by which pyroptosis modulation can attenuate chemotherapy resistance has not been comprehensively studied in OC. Here, we demonstrated that RAS‐associated C3 botulinum toxin substrate 1 (RAC1) is highly expressed in OC and is negatively correlated with patient outcomes. Through cell function tests and in vivo tumor formation tests, we found that RAC1 can promote tumor growth by mediating paclitaxel (PTX) resistance. RAC1 can mediate OC progression by inhibiting pyroptosis, as evidenced by high‐throughput automated confocal imaging, the release of lactate dehydrogenase (LDH), the expression of the inflammatory cytokines IL‐1β/IL‐18 and the nucleotide oligomerization domain‐like receptor family pyrin domain‐containing 3 (NLRP3) inflammasome. Mechanically, RNA‐seq, gene set enrichment analysis (GSEA), coimmunoprecipitation (Co‐IP), mass spectrometry (MS), and ubiquitination tests further confirmed that RAC1 inhibits caspase‐1/gasdermin D (GSDMD)‐mediated canonical pyroptosis through the P21‐activated kinase 4 (PAK4)/mitogen‐activated protein kinase (MAPK) pathway, thereby promoting PTX resistance in OC cells. Finally, the whole molecular pathway was verified by the results of in vivo drug combination tests, clinical specimen detection and the prognosis. In summary, our results suggest that the combination of RAC1 inhibitors with PTX can reverse PTX resistance by inducing pyroptosis through the PAK4/MAPK pathway. [ABSTRACT FROM AUTHOR]

As a resource-friendly consensus protocol, Proof-of-Authority (PoA) has been widely deployed in IoT applications with blockchain technology. It relies on a fixed set of trusted nodes called validators for block generation. In contrast to traditional consensus mechanisms, PoA offers better performance but also leads to a centralized blockchain. In a centralized blockchain, PoA gives a few authorities the power to tamper with all nodes. To improve the decentralization of the protocol, this paper proposes a proof of authority based on a dynamic set of validators (DyPoA). The protocol decouples the right to generate and commit blocks to the blockchain from the authority node in the original PoA. It enables unauthenticated nodes to perform the process of packing transactions into blocks, while authenticated nodes validate and commit blocks to the blockchain. Additionally, DyPoA introduces a contribution score mechanism to measure the work accomplished by each node when a block is appended to the blockchain. Based on the contribution score, DyPoA selects and replaces validators through cryptographic sortition. We evaluate DyPoA through decentralization metrics and performance tests. The experimental results show that the Shannon entropy, Gini coefficient, and Nakamoto coefficient of DyPoA are 1.5 times, 0.7 times, and 1.7 times that of the original PoA, respectively, and achieve a 2.2x throughput improvement and 3x latency reduction compared to the original PoA. [ABSTRACT FROM AUTHOR]

Background: Platinum-resistant or refractory ovarian cancer is a highly lethal gynecologic disease with limited treatment options. Chiauranib is a novel small-molecule selective inhibitor, which could effectively target multiple pathways including Aurora B and CSF-1R to inhibit cell cycle process and improve anti-tumor immune function, as long as VEGF pathway for tumor extinction. Methods: A phase II study was sequentially conducted after a phase Ib monotherapy study to evaluate the efficacy of chiauranib combined with chemotherapy. Chinese patients with recurrent ovarian cancer were enrolled. Eligible patients received chiauranib combined with a maximum of six cycles of chemotherapy: etoposide (CE group) or weekly-paclitaxel (CP group). Patients, who exhibited a complete or partial response, or stable disease following combo treatment, progressed to maintenance phase to receive chiauranib monotherapy. Primary endpoint was progression-free survival (PFS) according to RECIST v1.1. Results: From November 2017 to March 2019, 25 patients were enrolled in a phase 1b study and a median PFS of 3.7 months (95% CI 1.8–NE) was achieved by chiauranib monotherapy. From July 2019 to December 2020, a total of 47 patients were enrolled in the phase II study. One CP patient did not receive the study drugs, and three patients withdrew before the first tumor assessment. Thus, 43 patients (CE group: 22 patients; CP group: 21 patients) were included in the evaluation. The median PFS was 5·4 months (95% CI 2·8–5·6) and 5·6 months (95% CI 3·4–7·0), respectively. Conclusions: This was the first study to evaluate chiauranib, a novel multi-targeted kinase inhibitor in patients with ovarian cancer. The administration of chiauranib along with etoposide or weekly-paclitaxel significantly enhanced the efficacy with manageable adverse events. This warrants further clinical studies on this novel treatment. A phase III study is promising and ongoing. Trial registration: ClinicaTrials.gov identifier: NCT03901118 (phase II) and NCT03166891 (phase Ib). [ABSTRACT FROM AUTHOR]

High-entropy alloy nitride (HEN) coating of (AlCrTiVZr)N was deposited onto 17-4PH stainless steel substrates using the cathodic arc evaporation (CAE) technique. The composition and resulting microstructure were analyzed, and key mechanical properties including solid particle erosion resistance and sliding wear resistance were measured in the as-deposited condition. The coating had a relatively rough surface and contained small spherical droplets and large splats throughout the coating thickness. It had a single-phased solid solution B1 nitride phase with a preferred (111) orientation. The coating retained the as-deposited microstructure upon high temperature annealing, but experienced nitride phase decomposition at a temperature 800 °C or above. The hardness of the as-deposited nitride fell into the range of 27.5 ± 2.10 GPa and its elastic modulus was 284 ± 23 GPa. Dry sliding wear tests revealed the higher wear rates of the coating when compared with the wear rates of TiN coatings under various testing conditions. The coating had an erosion rate that increased with the impingement angle and demonstrated a combination of ductile and brittle erosion damage modes. Comparing to the CAE deposited TiN coating, the HEN nitride coating showed a lower wear and erosion resistance, which is attributed to the presence of a large quantity of defects in the coating. Reducing number of droplets/splats becomes very important for having better high-entropy nitride coating quality and hence the better coating performance against wear and erosion. [ABSTRACT FROM AUTHOR]

Background: Radioresistance is the leading cause of death in advanced cervical cancer (CC). Dysregulation of RNA modification has recently emerged as a regulatory mechanism in radiation and drug resistance. We aimed to explore the biological function and clinical significance of 5-methylcytosine (m5C) in cervical cancer radiosensitivity. Methods: The abundance of RNA modification in radiotherapy-resistant and sensitive CC specimens was quantified by liquid chromatography-tandem mass spectrometry. The essential RNA modification-related genes involved in CC radiosensitivity were screened via RNA sequencing. The effect of NSUN6 on radiosensitivity was verified in CC cell lines, cell-derived xenograft (CDX), and 3D bioprinted patient-derived organoid (PDO). The mechanisms of NSUN6 in regulating CC radiosensitivity were investigated by integrative m5C sequencing, mRNA sequencing, and RNA immunoprecipitation. Results: We found a higher abundance of m5C modification in resistant CC samples, and NSUN6 was the essential m5C-regulating gene concerning radiosensitivity. NSUN6 overexpression was clinically correlated with radioresistance and poor prognosis in cervical cancer. Functionally, higher NSUN6 expression was associated with radioresistance in the 3D PDO model of cervical cancer. Moreover, silencing NSUN6 increased CC radiosensitivity in vivo and in vitro. Mechanistically, NDRG1 was one of the downstream target genes of NSUN6 identified by integrated m5C-seq, mRNA-seq, and functional validation. NSUN6 promoted the m5C modification of NDRG1 mRNA, and the m5C reader ALYREF bound explicitly to the m5C-labeled NDRG1 mRNA and enhanced NDRG1 mRNA stability. NDRG1 overexpression promoted homologous recombination-mediated DNA repair, which in turn led to radioresistance in cervical cancer. Conclusions: Aberrant m5C hypermethylation and NSUN6 overexpression drive resistance to radiotherapy in cervical cancer. Elevated NSUN6 expression promotes radioresistance in cervical cancer by activating the NSUN6/ALYREF-m5C-NDRG1 pathway. The low expression of NSUN6 in cervical cancer indicates sensitivity to radiotherapy and a better prognosis. [ABSTRACT FROM AUTHOR]

In this work, we will consider the star network scenario where the central party is trusted while all the edge parties (with a number of n) are untrusted. Network steering is defined with an n local hidden state model which can be viewed as a special kind of n local hidden variable model. Two different types of sufficient criteria, nonlinear steering inequality and linear steering inequality will be constructed to verify the quantum steering in a star network. Based on the linear steering inequality, how to detect the network steering with a fixed measurement will be discussed. [ABSTRACT FROM AUTHOR]

Background: Poly (ADP-ribose) polymerase inhibitor (PARPi) resistance poses a significant challenge in ovarian carcinoma (OC). While the role of DOT1L in cancer and chemoresistance is acknowledged, its specific role in PARPi resistance remains unclear. This study aims to elucidate the molecular mechanism of DOT1L in PARPi resistance in OC patients. Methods: This study analyzed the expression of DOT1L in PARPi-resistant cell lines compared to sensitive ones and correlated it with clinical outcomes in OC patients. Comprehensive in vitro and in vivo functional experiments were conducted using cellular and mouse models. Molecular investigations, including RNA sequencing, chromatin immunoprecipitation (ChIP) and Cleavage Under Targets and Tagmentation (CUT&Tag) assays, were employed to unravel the molecular mechanisms of DOT1L-mediated PARPi resistance. Results: Our investigation revealed a robust correlation between DOT1L expression and clinical PARPi resistance in non-BRCA mutated OC cells. Upregulated DOT1L expression in PARPi-resistant tissues was associated with diminished survival in OC patients. Mechanistically, we identified that PARP1 directly binds to the DOT1L gene promoter, promoting transcription independently of its enzyme activity. PARP1 trapping induced by PARPi treatment amplified this binding, enhancing DOT1L transcription and contributing to drug resistance. Sequencing analysis revealed that DOT1L plays a crucial role in the transcriptional regulation of PLCG2 and ABCB1 via H3K79me2. This established the PARP1-DOT1L-PLCG2/ABCB1 axis as a key contributor to PARPi resistance. Furthermore, we discovered that combining a DOT1L inhibitor with PARPi demonstrated a synergistic effect in both cell line-derived xenograft mouse models (CDXs) and patient-derived organoids (PDOs). Conclusions: Our results demonstrate that DOT1L is an independent prognostic marker for OC patients. The PARP1-DOT1L/H3K79me2-PLCG2/ABCB1 axis is identified as a pivotal contributor to PARPi resistance. Targeted inhibition of DOT1L emerges as a promising therapeutic strategy for enhancing PARPi treatment outcomes in OC patients. [ABSTRACT FROM AUTHOR]

Background: Recent studies showed heterogeneity in stage IVB patients. However, few studies focused on the prognosis of supraclavicular metastatic ovarian cancer. This study aimed to explore the prognostic factors and the role of primary debulking in IVB ovarian cancer patients with supraclavicular lymph node metastasis. Methods: We retrospectively analyzed patients newly diagnosed as primary epithelial ovarian cancer with supraclavicular lymph node metastasis from January 2015 to July 2020. Supraclavicular lymph node metastasis was defined as either the pathological diagnosis by supraclavicular lymph node biopsy, or the radiological diagnosis by positron emission tomography-computed tomography (PET-CT). Results: In 51 patients, 37 was diagnosed with metastatic supraclavicular lymph nodes by histology, 46 by PET-CT, and 32 by both methods. Forty-four (86.3%) with simultaneous metastatic paraaortic lymph nodes (PALNs) by imaging before surgery or neoadjuvant chemotherapy were defined as "continuous-metastasis type", while the other 7 (13.7%) defined as "skip-metastasis type". Nineteen patients were confirmed with metastatic PALNs by histology. Thirty-four patients were investigated for BRCA mutation, 17 had germline or somatic BRCA1/2 mutations (g/sBRCAm). With a median follow-up of 30.0 months (6.3–63.4 m), 16 patients (31.4%) died. The median PFS and OS of the cohort were 17.3 and 48.9 months. Survival analysis showed that "continuous-metastasis type" had longer OS and PFS than "skip-metastasis type" (OS: 50.0/26.6 months, PFS: 18.5/7.2months, p=0.005/0.002). BRCA mutation carriers also had longer OS and PFS than noncarriers (OS: 57.4 /38.5 m, p=0.031; PFS: 23.6/15.2m, p=0.005). Multivariate analysis revealed only metastatic PALNs was independent prognostic factor for OS (p=0.040). Among "continuous-metastasis type" patients, 22 (50.0%) achieved R0 abdominopelvic debulking, who had significantly longer OS (55.3/42.3 months, p =0.034) than those with residual abdominopelvic tumors. Conclusions: In stage IVB ovarian cancer patients with supraclavicular lymph nodes metastasis, those defined as "continuous-metastasis type" with positive PALNs had better prognosis. For them, optimal abdominopelvic debulking had prognostic benefit, although metastatic supraclavicular lymph nodes were not resected. Higher BRCA mutation rate than the general population of ovarian cancer patients was observed in patients with IVB supraclavicular lymph node metastasis, leading to better survival as expected. [ABSTRACT FROM AUTHOR]

In the study of the deep learning classification of medical images, deep learning models are applied to analyze images, aiming to achieve the goals of assisting diagnosis and preoperative assessment. Currently, most research classifies and predicts normal and cancer cells by inputting single-parameter images into trained models. However, for ovarian cancer (OC), identifying its different subtypes is crucial for predicting disease prognosis. In particular, the need to distinguish high-grade serous carcinoma from clear cell carcinoma preoperatively through non-invasive means has not been fully addressed. This study proposes a deep learning (DL) method based on the fusion of multi-parametric magnetic resonance imaging (mpMRI) data, aimed at improving the accuracy of preoperative ovarian cancer subtype classification. By constructing a new deep learning network architecture that integrates various sequence features, this architecture achieves the high-precision prediction of the typing of high-grade serous carcinoma and clear cell carcinoma, achieving an AUC of 91.62% and an AP of 95.13% in the classification of ovarian cancer subtypes. [ABSTRACT FROM AUTHOR]

Summary: In this paper, introduces a DC–DC converter design based on a modified hybrid switched inductor‐switched capacitor architecture, aimed at achieving ultra‐high voltage gain in renewable energy systems (RES). The proposed converter involves adding a modified boosting conversion mode (MBM) that interleaves with the main switch to double the voltage transfer gain. Additionally, a modified switched capacitor (MSC) technique, utilizing two diodes as interleaved components, is integrated into the main and auxiliary switches to verify low voltage stress across them. In addition, modified hybrid switched inductors with capacitors (MSIC) and diodes are employed to validate ultra‐high voltage gain. The main advantages of the proposed converter are its high efficiency, low voltage stress across diodes and MOSFETs, and the utilization of low values of inductors and capacitors at high switching frequencies. In addition, the voltage stress across the inductors of the (MSIC) is reduced as the duty cycle increases. Furthermore, the current stress on the main switch is reduced when the charge of capacitor C1 becomes zero. Mathematical models for both continuous conduction mode (CCM) and discontinuous conduction mode (DCM) of the proposed converter are explored. Furthermore, a dual PI controller is designed for the proposed converter to maintain a high fixed output voltage. In addition, the PCB design and experimental testing of the proposed converter to verify the simulation and laboratory results. Specifically, the proposed converter is designed to boost up voltage (30–40 V) to a variable output voltage between 200 and 300 V at 300 W at efficiency 96.7%. [ABSTRACT FROM AUTHOR]

To elucidate the hydrochemical characteristics, controlling factors, sources and mechanisms of strontium ion enrichment in groundwater in the northwest plain of Shandong Province, China, 88 groundwater samples were collected, including 51 shallow pore groundwater samples, 29 deep pore groundwater samples and 8 karst groundwater samples. The hydrochemical characteristics of the different types of groundwater were quite different. The karst groundwater samples were all fresh water with a single hydrochemical type, either HCO3-Ca or HCO3-Ca·Mg. The deep pore groundwater samples were mainly brackish water, and the shallow pore groundwater samples were brackish water–salt water, which has complex hydrochemical types. The hydrochemical characteristics of all the types of groundwater were controlled by mineral dissolution and active positive cation exchange. In shallow pore groundwater, deep pore groundwater and karst groundwater, the dissolution of silicate, evaporite and carbonate minerals dominated the hydrogeochemical process. The strontium in groundwater was derived from the dissolution of minerals with strontium isomorphism. The average contents of strontium in shallow, deep and karst groundwater were 1.59 mg/L, 0.58 mg/L and 0.50 mg/L, respectively. The strontium in shallow pore groundwater was mainly derived from the enrichment of groundwater runoff, and its sources are abundant, with silicic rock being the main source. The deep pore groundwater mainly derived from the evaporative minerals containing strontium, and the karst water mainly derived from carbonate rock dissolution with similar characteristics. [ABSTRACT FROM AUTHOR]

A high-efficiency DC-DC converter employing a modified architecture called the hybrid switched inductor–capacitor series (MHSLCS) is proposed in this paper. The primary goal is to achieve a notably ultra-high voltage gain for renewable energy systems (RESs). Furthermore, the use of only one input capacitor in the MHSLCS eliminates pulsations in the input current at both low and high duty ratios. The proposed converter integrates the MHSLCS with a modified switched capacitor (MSC) that interleaves with the main MOSFET, effectively doubling the voltage transfer gain. Additionally, a modified hybrid switched inductor–capacitor parallel (MHSLCP) is incorporated in parallel with an interleaved auxiliary MOSFET. Both MOSFETs, combined with the MSC, contribute to achieving an ultra-high voltage gain. In addition, the inductors of the MHSLCP operate in a discontinuous conduction mode (DCM), which results in significant stress reductions in the power diodes and switches at high output voltages. The advantages of the proposed converter are multifaceted, demonstrating a high efficiency while minimizing the voltage in power device diodes and MOSFETs. The use of low inductance and capacitance values at high switching frequencies further enhances the performance. Wide-bandgap (WBG) power devices are employed to achieve the desired high voltage gain and efficiency. The proposed converter was designed with a PCB and underwent experimental testing to validate laboratory results. The proposed converter boosted the input voltage from 30 V to a variable output voltage between 325 V and 500 V, with a power output of 325 watts and an efficiency of 95.5%. [ABSTRACT FROM AUTHOR]

Purpose: To study the clinicopathological variables connected with disease-free survival (DFS) as well as overall survival (OS) in patients who are ER-positive or HER2-negative and to propose nomograms for predicting individual risk. Methods: In this investigation, we examined 585 (development cohort) and 291 (external validation) ER-positive, HER2-negative breast cancer patients from January 2010 to January 2014. From January 2010 to December 2014, we retrospectively reviewed and analyzed 291 (external validation) and 585 (development cohort) HER2-negative, ER-positive breast cancer patients. Cox regression analysis, both multivariate and univariate, confirmed the independence indicators for OS and DFS. Results: Using cox regression analysis, both multivariate and univariate, the following variables were combined to predict the DFS of development cohort: pathological stage (HR = 1.391; 95% CI = 1.043–1.855; P value = 0.025), luminal parting (HR = 1.836; 95% CI = 1.142–2.952; P value =.012), and clinical stage (HR = 1.879; 95% CI = 1.102–3.203; P value = 0.021). Endocrine therapy (HR = 3.655; 95% CI = 1.084–12.324; P value = 0.037) and clinical stage (HR = 6.792; 95% CI = 1.672–28.345; P value = 0.009) were chosen as predictors of OS. Furthermore, we generated RS-OS and RS-DFS. According to the findings of Kaplan–Meier curves, patients who are classified as having a low risk have considerably longer DFS and OS durations than patients who are classified as having a high risk. Conclusion: To generate nomograms that predicted DFS and OS, independent predictors of DFS in ER-positive/HER2-negative breast cancer patients were chosen. The nomograms successfully stratified patients into prognostic categories and worked well in both internal validation and external validation. [ABSTRACT FROM AUTHOR]

Single photon sources operating on-demand at telecom wavelengths are required in fiber-based quantum secure communication technologies. In this work, we demonstrate single photon emission from position-controlled nanowire quantum dots emitting at λ > 1530 nm. Emission in the C-band is achieved by composition engineering of an InAsxP1−x dot-in-a-rod structure. Using above-band pulsed excitation, we obtain single photon purities of g (2) (0) = 0.062. These results represent an important step toward the scalable manufacture of high efficiency, high rate single photon emitters in the telecom C-band. [ABSTRACT FROM AUTHOR]

As a core component of photovoltaic power generation systems, insulated gate bipolar transistor (IGBT) modules continually suffer from severe temperature swings due to complex operation conditions and various environmental conditions, resulting in fatigue failure. The junction temperature prediction guarantees that the IGBT module operates within the safety threshold. The thermal equivalent circuit model is a common approach to predicting junction temperature. However, the model parameters are easily affected by the solder aging. An accurate temperature prediction by the model is impossible during service. This paper proposes an improved thermal equivalent circuit model that can remove the effect of solder aging. Firstly, the solder aging process is monitored in real-time based on the case temperatures. Secondly, the model parameters are corrected by the thermal impedance from chip to baseplate based on the linear thermal characteristic. The simulation and experimental results show that the proposed model can reduce the temperature prediction error by more than 90% under the same aging condition. The proposed method only depends on the case temperatures to correct the model parameters, which is more economical. In addition, the experimental and simulation analysis in this work can help students of power electronics courses have an in-depth knowledge of power devices' mechanical structure, heat dissipation principles, temperature distribution, junction temperature monitoring, and so on. [ABSTRACT FROM AUTHOR]

As part of the non-clinical safety package characterizing bamlanivimab (SARS-CoV-2 neutralizing monoclonal antibody), the risk profile for antibody-dependent enhancement of infection (ADE) was evaluated in vitro and in an African green monkey (AGM) model of COVID-19. In vitro ADE assays in primary human macrophage, Raji, or THP-1 cells were used to evaluate enhancement of viral infection. Bamlanivimab binding to C1q, FcR, and cell-based effector activity was also assessed. In AGMs, the impact of bamlanivimab pretreatment on viral loads and clinical and histological pathology was assessed to evaluate enhanced SARS-CoV-2 replication or pathology. Bamlanivimab did not increase viral replication in vitro, despite a demonstrated effector function. In vivo, no significant differences were found among the AGM groups for weight, temperature, or food intake. Treatment with bamlanivimab reduced viral loads in nasal and oral swabs and BAL fluid relative to control groups. Viral antigen was not detected in lung tissue from animals treated with the highest dose of bamlanivimab. Bamlanivimab did not induce ADE of SARS-CoV-2 infection in vitro or in an AGM model of infection at any dose evaluated. The findings suggest that high-affinity monoclonal antibodies pose a low risk of mediating ADE in patients and support their safety profile as a treatment of COVID-19 disease. [ABSTRACT FROM AUTHOR]

In this study, we assessed the effects of MFG-E8 on the biological characteristics of ovarian cancer cells and explored the underlying mechanisms. Human ovarian cancer SKOV3 cells were transfected with MFG-E8 siRNA or NC siRNA. CCK-8, cell adhesion, scratch-wound, and Transwell assays were used to detect changes in cell metastatic processes. Effects of MFG-E8 silencing on the proteins involved in AKT/mTOR/S6K signalling pathway were assessed using qRT-PCR and Western blotting. Transient silencing of MFG-E8 in SKOV3 cells decreased cell proliferation and downregulated the expression of CDK4, cyclin D1, and caspase-3 proteins. Cell adhesion, migration, and invasion were also suppressed. p-AKT, p-mTORC1, and p-p70S6K levels decreased following MFG-E8 knockdown. Hence, MFG-E8 enhances carcinogenesis and affects the AKT/mTOR/S6K signalling pathway in ovarian cancer cells. In conclusion, our results suggested that MFG-E8 could promote ovarian cancer via AKT/mTOR/S6K signalling pathway which improved our understanding of the molecular mechanisms involved in ovarian cancer. What is already known on this subject? Milk fat globule-epidermal growth factor 8 (MFG-E8) is expressed in several types of cancers such as oesophageal, breast, and liver. However, the mechanism of MFG-E8 involving in EOC remains unknown. We previously found that MFG-E8 expression was related to pathological staging, tissue differentiation, platinum sensitivity, ascites state, and other clinicopathological characteristics. What the results of this study add? Due to a series of in vitro studies, we confirmed that MFG-E8 is involved in the process of proliferation, invasion and metastasis. Our results show that silencing MFG-E8 can significantly inhibit the expression of cyclin D1 and CDK4 in EOC SKOV3 cells. MFG-E8 enhances carcinogenesis and affects the AKT/mTOR/S6K signaling pathway in ovarian cancer. What the implications are of these findings for clinical practice and/or further research? Taken together, our findings suggest that MFG-E8 may be an oncogene in EOC and provide new insights into the mechanism of MFG-E8 in the progression of EOC. [ABSTRACT FROM AUTHOR]

Vaccination is a fundamental tool in preventing infectious diseases. However, due to the wide array of vaccines available, comprehending the entire vaccine landscape can be a daunting task. To tackle this complexity, this study employs advanced network analysis methods capable of capturing the intricate relationships within multivariate datasets. The objective is to investigate how the vaccination landscape has evolved both before and after the COVID-19 pandemic. This study examined vaccination data in the Nanan District of Chongqing, China, spanning from 2016 to 2022. Additionally, the network topological characteristics were computed and scrutinized across 2326 sliding windows. The investigation focused on assessing alterations in the topological structure of the vaccination network before and after the COVID-19 pandemic, encompassing analyses at both macro and mesoscale levels. Furthermore, at the micro level, this study delved into the correlation degrees of selected vaccine nodes within the vaccination network. The analysis unveiled that the correlation and activity within the vaccination network showed a noticeable enhancement in strength in the wake of the COVID-19 pandemic, especially during the spring and winter months. However, the community structure and the average interactions between vaccines displayed a diminishing trend post-pandemic. Among the analyzed vaccines, the HepA vaccine emerged as the one with the highest average node-degree centrality rank. A closer examination of the node-degree centrality ranking chart within the vaccination network disclosed fluctuations in the rankings of various vaccine types across different time periods and seasons. In contrast, vaccines incorporated into NIP exhibited a remarkable degree of consistency, which is attributed to children adhering to a fixed vaccination schedule, rendering NIP vaccines less susceptible to disruptions and enhancing their stability within the vaccination network. This study offers valuable insights into the dynamics of the vaccination network, shedding light on the impact of the COVID-19 pandemic, seasonal variations, and the ever-shifting correlation patterns among different vaccine types. These discoveries enrich our comprehension of vaccination trends and have the potential to guide forthcoming endeavors aimed at refining vaccination strategies and enhancing public health outcomes, not only in the Nanan District but also in analogous settings. [ABSTRACT FROM AUTHOR]

Background: According to the World Health Organization, foodborne disease is a significant public health issue. We will choose the best model to predict foodborne disease by comparison, to provide evidence for government policies to prevent foodborne illness. Methods: The foodborne disease monthly incidence data from June 2017 to April 2022 were obtained from the Chongqing Nan'an District Center for Disease Prevention and Control. Data from June 2017 to June 2021 were used to train the model, and the last 10 months of incidence were used for prediction and validation The incidence was fitted using the seasonal autoregressive integrated moving average (SARIMA) model, Holt-Winters model and Exponential Smoothing (ETS) model. Besides, we used MSE, MAE, RMSE to determine which model fits better. Results: During June 2017 to April 2022, the incidence of foodborne disease showed seasonal changes, the months with the highest incidence are June to November. The optimal model of SARIMA is SARIMA (1,0,0) (1,1,0)12. The MSE, MAE, RMSE of the Holt-Winters model are 8.78, 2.33 and 2.96 respectively, which less than those of the SARIMA and ETS model, and its prediction curve is closer to the true value. The optimal model has good predictive performance. Conclusion: Based on the results, Holt-Winters model produces better prediction accuracy of the model. [ABSTRACT FROM AUTHOR]

One major characteristic of tumor cells is the aberrant activation of epigenetic regulatory elements, which remodel the tumor transcriptome and ultimately promote cancer progression and drug resistance. However, the oncogenic functions and mechanisms of ovarian cancer (OC) remain elusive. Here, super‐enhancer (SE) regulatory elements that are aberrantly activated in OC are identified and it is found that SEs drive the relative specific expression of the transcription factor KLF5 in OC patients and poly(ADP‐ribose) polymerase inhibitor (PARPi)‐resistant patients. KLF5 expression is associated with poor outcomes in OC patients and can drive tumor progression in vitro and in vivo. Mechanistically, KLF5 forms a transcriptional complex with EHF and ELF3 and binds to the promoter region of RAD51 to enhance its transcription, strengthening the homologous recombination repair (HRR) pathway. Notably, the combination of suberoylanilide hydroxamic acid (SAHA) and olaparib significantly inhibits tumor growth and metastasis of PARPi‐resistant OC cells with high KLF5. In conclusion, it is discovered that SEs‐driven KLF5 is a key regulatory factor in OC progression and PARPi resistance; and potential therapeutic strategies for OC patients with PARPi resistance and high KLF5 are identified. [ABSTRACT FROM AUTHOR]

Tracer pathline statistics have rarely, if at all, been used in the investigation of compressible subsonic, transonic and supersonic flows past a circular cylinder. Here, we report pathline histogram, conditional histogram and zonal histogram data, focusing on the characteristics of particle instantaneous flow reversal and their dependencies on Mach number and tracer release position. The far-upstream Mach number and the diameter-based Reynolds number used for these three flow regimes are $ ({0.2, 10000}), ({0.9, 3900}) $ (0.2 , 10000) , (0.9 , 3900) and $ ({1.2, 10000}) $ (1.2 , 10000) , respectively. The subsonic surface-release histogram profiles display unexpected persistent oscillations at a frequency $ 50 $ 50 times of the periodic vortex shedding frequency, reflecting the effect of a very small magnitude zig-zagging type of particle motion in a region very close to the wall and slightly behind the mean flow separation location. No similar high-frequency oscillation is observed in the corresponding transonic and supersonic histograms likely because, at $ \textrm{Ma} \ge 0.9 $ Ma ≥ 0.9 , periodic vortex shedding ceases to exist and the near-wake becomes a quasi-laminar recirculation zone bounded by a pair of converging slip-layers with a neck opening to the far-wake. At the instant of $ 5 $ 5 subsonic vortex-shedding periods after being released from the cylinder surface, there are $ 1.67\% $ 1.67 % , $ 35.2\% $ 35.2 % and $ 39.7\% $ 39.7 % particles that experience flow reversal in the subsonic, transonic and supersonic flows, respectively. Surprisingly, in the present transonic flow, growth of the turbulent far-wake behind the pair of lambda-shocks is constrained over a considerable streamwise distance. [ABSTRACT FROM AUTHOR]

One of the most important causes of the failure of power electronic modules is thermal stress. Proper thermal management plays an important role in more reliable and cost-effective energy conversion. In this paper, we present an advanced active thermal control (ATC) strategy to reduce a power device's thermal stress amplitude during operation, with the aim of improving the reliability and lifetime of the conversion system. A state-space model based on a Foster-type thermal model is developed to achieve junction temperature estimation in real time. A feedback controller based on finite-time boundedness (FTB) is proposed to precisely regulate the temperature in order to reduce the thermal stress according to the temperature profile. The designed controller permits the precise control of the temperature and strongly reduces the thermal stress during fast transients in the power demand. Simulation and experimental results are provided to validate the effectiveness of the proposed method. [ABSTRACT FROM AUTHOR]

Image dehazing models are critical in improving the recognition and classification capabilities of image-related artificial intelligence systems. However, existing methods often ignore the limitations of receptive field size during feature extraction and the loss of important information during network sampling, resulting in incomplete or structurally flawed dehazing outcomes. To address these challenges, we propose a multi-level perception fusion dehazing network (MPFDN) that effectively integrates feature information across different scales, expands the perceptual field of the network, and fully extracts the spatial background information of the image. Moreover, we employ an error feedback mechanism and a feature compensator to address the loss of features during the image dehazing process. Finally, we subtract the original hazy image from the generated residual image to obtain a high-quality dehazed image. Based on extensive experimentation, our proposed method has demonstrated outstanding performance not only on synthesizing dehazing datasets, but also on non-homogeneous haze datasets. [ABSTRACT FROM AUTHOR]

This paper introduces an optimized DC–DC converter that employs a modified switched inductor-capacitor technique to achieve ultra-high voltage gain for renewable energy systems. The development is based on adding one cell of modified switched inductor (MSL1) with series diodes interleaved with the main switch in the proposed DC–DC converter. The (MSL1) with capacitor operates in resonant mode to reduce current stress across the main switch when the charge in capacitor becomes zero. This approach also reduces voltage stress across the main switch, all inductors, and diodes. Furthermore, modified switched inductors (MSL2) with an auxiliary switch and a coupled capacitor are incorporated to provide double boosting voltage and to achieve high voltage gain. Additionally, a main and auxiliary switch are integrated with modified switched capacitors (MSC) to provide ultra-high voltage gain and to reduce voltage stress across auxiliary switch. Moreover, the proposed converter exhibits a continuous input current with zero pulsating, even at very low duty cycles. The advantages of the proposed converter are high efficiency, low voltage stress, and low values of inductors and capacitors when utilizing a high switching frequency. A mathematical model for the proposed converter is developed for both continuous conduction mode and discontinuous conduction mode. In addition, the PCB design for the proposed converter is presented, and experimental tests are conducted to verify the simulation and laboratory results. The proposed converter aims to boost the voltage from 20 to 40 V to a variable output voltage between 200 and 400 V, delivering 400 watts of power with an efficiency of 96.2%. [ABSTRACT FROM AUTHOR]

Background: Cervical cancer is one of the most common gynecological cancers threatening women's health worldwide. Double-stranded RNA-binding proteins (dsRBPs) regulate innate immunity and are therefore believed to be involved in virus-related malignancies, however, their role in cervical cancer is not well known. Methods: We performed RNA-seq of tumor samples from cervical cancer patients in local cohort and also assessed the RNA-seq and clinical data derived from public datasets. By using single sample Gene Set Enrichment Analysis (ssGSEA) and univariate Cox analysis, patients were stratified into distinct dsRBP clusters. Stepwise Cox and CoxBoost were performed to construct a risk model based on optimal dsRBPs clusters-related differentially expressed genes (DEGs), and GSE44001 and CGCI-HTMCP-CC were employed as two external validation cohorts. Single cell RNA sequencing data from GSE168652 and Scissor algorithm were applied to evaluated the signature-related cell population. Results: The expression of dsRBP features was found to be associated with HPV infection and carcinogenesis in CESC. However, only Adenosine deaminases acting on RNA (ADAR) and Dicer, Drosha, and Argonautes (DDR) exhibited significant correlations with the overall survival (OS) of CESC patients. Based on these findings, CESC patients were divided into three dsRBP clusters. Cluster 3 showed superior OS but lower levels of ADAR and DDR. Additionally, Cluster 3 demonstrated enhanced innate immunity, with significantly higher activity in cancer immunity cycles, immune scores, and levels of tumor-infiltrating immune cells, particularly CD8+ T cells. Furthermore, a risk model based on nine dsRBP cluster-related DEGs was established. The accuracy of survival prediction for 1 to 5 years was consistently above 0.78, and this model's robust predictive capacity was confirmed by two external validation sets. The low-risk group exhibited significantly higher levels of immune checkpoints, such as PDCD1 and CTLA4, as well as a higher abundance of CD8+ T cells. Analysis of single-cell sequencing data revealed a significant association between the dsRBP signature and glycolysis. Importantly, low-risk patients showed improved OS and a higher response rate to immunotherapy, along with enduring clinical benefits from concurrent chemoradiotherapy. Conclusions: dsRBP played a crucial role in the regulation of prognosis and tumor immunology in cervical cancer, and its prognostic signature provides a strategy for risk stratification and immunotherapy evaluation. [ABSTRACT FROM AUTHOR]

Backgrounds: Endometrial carcinoma (EC) is one of the most commonly diagnosed gynecologic malignancy in China. However, the genetic profile of Chinese EC patients has not been well established yet. Methods: In current study, 158 Chinese EC patients were subjected to next-generation sequencing assay (74 took testing of EC-related 20-genes panel, and 84 took the expanded panel). Of the 158 patients, 91 patients were performed germline mutation testing using the expanded panel. Moreover, the public datasets from TCGA and MSKCC were utilized to compare the genomic differences between Chinese and Western EC patients. The proteomic and transcriptomic from CPTAC and TCGA were derived and performed unsupervised clustering to identify molecular subtypes. Results: Among the 158 patients analyzed, a significant majority (85.4%) exihibited at least one somatic alteration, with the most prevalent alterations occurring in PTEN, PIK3CA, TP53, and ARID1A. These genomic alterations were mainly enriched in the PI3K, cell cycle, RAS/RAF/MAPK, Epigenetic modifiers/Chromatin remodelers, and DNA damage repair (DDR) signaling pathways. Additionally, we identified ten individuals (11.0%) with pathogenic or likely pathogenic germline alterations in seven genes, with the DDR pathway being predominantly involved. Compared to Western EC patients, Chinese EC patients displayed different prevalence in AKT1, MET, PMS2, PIK3R1, and CTCF. Notably, 69.6% of Chinese EC patients were identified with actionable alterations. In addition, we discovered novel molecular subtypes in ARID1A wild-type patients, characterized by an inferior prognosis, higher TP53 but fewer PTEN and PIK3CA alterations. Additionally, this subtype exhibited a significantly higher abundance of macrophages and activated dendritic cells. Conclusion: Our study has contributed valuable insights into the unique germline and somatic genomic profiles of Chinese EC patients, enhancing our understanding of their biological characteristics and potential therapeutic avenues. Furthermore, we have highlighted the presence of molecular heterogeneity in ARID1A-wild type EC patients, shedding light on the complexity of this subgroup. [ABSTRACT FROM AUTHOR]

In the vertebrate brain, sensory experience plays a crucial role in shaping thalamocortical connections for visual processing. However, it is still not clear how visual experience influences tissue homeostasis and neurogenesis in the developing thalamus. Here, we reported that the majority of SOX2-positive cells in the thalamus are differentiated neurons that receive visual inputs as early as stage 47 Xenopus. Visual deprivation (VD) for 2 days shifts the neurogenic balance toward proliferation at the expense of differentiation, which is accompanied by a reduction in nuclear-accumulated β-catenin in SOX2-positive neurons. The knockdown of β-catenin decreases the expression of SOX2 and increases the number of progenitor cells. Coimmunoprecipitation studies reveal the evolutionary conservation of strong interactions between β-catenin and SOX2. These findings indicate that β-catenin interacts with SOX2 to maintain homeostatic neurogenesis during thalamus development. [ABSTRACT FROM AUTHOR]

Cloud computing is popular because it can provide low-cost, high-performance data processing services. However, since cloud computing transactions between users and service providers are usually asynchronous, data privacy and online payment issues involving users and service providers often lead to a crisis of trust, which may hinder the development of cloud computing and application. Most existing solutions only consider a certain type of service or solving one of them. In this paper, we propose BPF-Payment, a fair payment scheme for cloud computing with privacy based on blockchain and homomorphic encryption, which achieves correctness, fairness, compatibility, and a lightweight client. BPF-Payment solves the problem of unfair payment in cloud computing by introducing blockchain as a third party. It also uses the Paillier homomorphic encryption scheme to enable blockchain to perform verification of problem solutions without accessing problem-related data, thereby ensuring data privacy. To verify the security and practicability of BPF-Payment, we instantiate BPF-Payment based on the Paillier homomorphic encryption scheme and evaluate the implementation. We test the performance of key generation, encryption and decryption, and verification in the BPF-Payment scheme on the FISCO-BOCS blockchain. The experimental results show that the time and gas consumption of BPF-Payment are reasonable and acceptable. [ABSTRACT FROM AUTHOR]

A scalable segmented-based proton-exchange membrane fuel cell (PEMFC) hybrid power system model is developed in this paper. The fuel cell (FC) is developed as a dynamic lumped parameter model to predict the current distributions during dynamic load scenarios. The fuel cell is segmented into 3 × 3 segments connected with several physical ports and with the variables balanced automatically. Based on the proposed model, a real-time energy management framework is designed to distribute the load current demand during dynamic operations. Simulation results show that the proposed strategy has good performance on both single/segmented fuel cell–battery hybrid systems and the low battery state of charge (SOC) situation. This paper proposes an approach that uses an interconnected ordinary differential equations (ODEs) system model in control problems, which makes the control algorithms readily applicable. [ABSTRACT FROM AUTHOR]

Background: Increasing evidences has indicated that primary and acquired resistance of ovarian cancer (OC) to platinum is mediated by multiple molecular and cellular factors. Understanding these mechanisms could promote the therapeutic efficiency for patients with OC. Methods: Here, we screened the expression pattern of circRNAs in samples derived from platinum-resistant and platinum-sensitive OC patients using RNA-sequencing (RNA-seq). The expression of hsa_circ_0010467 was validated by Sanger sequencing, RT-qPCR, and fluorescence in situ hybridization (FISH) assays. Overexpression and knockdown experiments were performed to explore the function of hsa_circ_0010467. The effects of hsa_circ_0010467 on enhancing platinum treatment were validated in OC cells, mouse model and patient-derived organoid (PDO). RNA pull-down, RNA immunoprecipitation (RIP), and dual-luciferase reporter assays were performed to investigate the interaction between hsa_circ_0010467 and proteins. Results: Increased expression of hsa_circ_0010467 is observed in platinum-resistant OC cells, tissues and serum exosomes, which is positively correlated with advanced tumor stage and poor prognosis of OC patients. Hsa_circ_0010467 is found to maintain the platinum resistance via inducing tumor cell stemness, and silencing hsa_circ_0010467 substantially increases the efficacy of platinum treatment on inhibiting OC cell proliferation. Further investigation reveals that hsa_circ_0010467 acts as a miR-637 sponge to mediate the repressive effect of miR-637 on leukemia inhibitory factor (LIF) and activates the LIF/STAT3 signaling pathway. We further discover that AUF1 could promote the biogenesis of hsa_circ_0010467 in OC. Conclusion: Our study uncovers the mechanism that hsa_circ_0010467 mediates the platinum resistance of OC through AUF1/hsa_circ_0010467/miR-637/LIF/STAT3 axis, and provides potential targets for the treatment of platinum-resistant OC patients. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Primary HCO is a rare, aggressive ovarian malignant tumor, morphologically resembling HCC. SALL4 can be adopted to differentiate HCO from HCC. The serum AFP and CA125 rather than HE4 can be employed as possible biomarkers to track treatment and monitor recurrence. We report a case of a postmenopausal woman presenting with lower abdominal pain and vaginal bleeding. She went through a maximal debulking surgery, and the pathological biopsy revealed hepatoid carcinoma of the ovary (HCO). Immunohistochemical assay demonstrates SALL4 as an indicator to differentiate HCO from hepatocellular carcinoma (HCC). [ABSTRACT FROM AUTHOR]

The magnetic order in 2D material CrI3 has a significant impact on the Raman polarization selection rules of phonons, as evidenced by magneto-optical Raman spectroscopy. In a monolayer, the forbidden Raman scattering of A1g mode can be detected in the XY channel at low temperatures. However, in the bilayer, the Ag mode splits into two modes, and the selection rules of the splitting modes are determined by the magnetic order and symmetry. In contrast, the inversion symmetry of the spin structure is maintained in both antiferromagnetic (AFM) and ferromagnetic (FM) states in the trilayer (3L) CrI3, and the evolution of its Raman scattering with magnetic field is not yet clear. In this work, we use magneto-optical polarized Raman spectroscopy and reflective magnetic circular dichroism to investigate the Davydov splitting of the Ag phonon mode and its coupling to layered magnetism in 2–5L CrI3. Our results show that the Raman scattering of the Ag mode is strongly coupled to the layered magnetic order, indicating strong spin–phonon coupling in CrI3. Our study might shed light on the research on interaction between magnetic and vibrational properties of 2D magnetic materials and provide important implications for developing novel 2D spintronic devices. [ABSTRACT FROM AUTHOR]

In this paper, a new single-cell hybrid switched inductor DC-DC converter is proposed to demonstrate the verification of ultra-high voltage gain in renewable energy applications (REA). The modification involves adding a single cell of an inductor with a diode and double capacitor to increase voltage transfer gain. Additionally, this modification helps prevent the input current from becoming zero, pulsating at very low duty cycles. The single cell of the hybrid inductor is interleaved with the main switch to reduce current stress when the capacitor of the single-cell inductor charge becomes zero. Moreover, the addition of a modified hybrid switch inductor with a capacitor, operating in dual boosting mode with a single switch, allows the converter to achieve ultra-high voltage gain. The proposed converter offers several advantages, including ultra-high voltage gain, high efficiency, low voltage stress on power MOSFETs, diodes, inductors, and capacitors, as well as low switching and conduction losses. Furthermore, the proposed converter utilizes transformerless and non-coupled inductors. Mathematical equations have been derived for the discontinuous conduction mode (DCM) and continuous conduction mode (CCM) and implemented using Matlab Simulink software to validate the results. In addition, a dual PI controller is designed for the proposed converter to verify the fixed output voltage. Experimental results have also been obtained for a 200 W prototype, with the input voltage varying between 20 V and 40 V, and an output voltage of 200 V at an efficiency of 96.5%. [ABSTRACT FROM AUTHOR]

Introduction: Tranexamic acid reduces blood loss and allogeneic transfusion requirements in various surgical procedures. The role of tranexamic acid during cytoreductive procedures in advanced ovarian cancer is not clear. Material and methods: This was a single center randomized, controlled, three‐armed clinical trial. A total of 150 ovarian cancer patients undergoing cytoreductive surgery were recruited and assigned to three groups (n = 50/group): the control group (normal saline), low‐dose group (10 mg/kg bolus + 1 mg/kg continuous infusion of tranexamic acid), and high‐dose group (20 mg/kg bolus + 5 mg/kg continuous infusion of tranexamic acid). The primary endpoint was intraoperative blood loss volume and total blood loss volume, and secondary endpoints included intraoperative blood transfusion volumes, vasoactive agent consumption, admission into the intensive care unit, and incidence of postoperative complications within postoperative 30 days. The study was registered at ClinicalTrials.gov ID: NCT04360629. Results: The patients in the high‐dose group had less intraoperative (median [IQR]: 625.3 mL [343.5–1210.5]) and total blood loss volume (748.9 mL [292.2–1650.2]) than those in the control group (1015.5 mL [679.4–1015.5], p = 0.012; and 1700.7 mL [458.7–2419.8], p = 0.004, respectively). In contrast, the intraoperative (992.5 mL [539.0–1404.0], p = 0.874) and total blood loss volume (1025.0 mL [381.8–1819.9], p = 0.113) was not significantly reduced in the low‐dose group when compared with the control group. Correspondingly, the relative risk of blood transfusion (RR [95% CI], 0.405 [0.180–0.909], p = 0.028) was reduced in the high‐dose group and required less intraoperative noradrenaline (881.0 ± 438.3 mg) to maintain stable hemodynamics than the control group (1548.0 ± 349.8 mg, p = 0.001). Furthermore, compared with the control group, the two tranexamic acid groups had decreased intensive care unit admission rates (p = 0.016) without increasing the incidence of postoperative seizure, acute kidney injury, and thromboembolism. Conclusions: High‐dose tranexamic acid is more effective in reducing blood loss and blood transfusion without increasing the risk of postoperative complications. The high‐dose regime tended to have a better risk–benefit profile. [ABSTRACT FROM AUTHOR]