Restriction on molecular fluxionality by substitution: A case study for the 1,10-dicyanobullvalene.

We show herein that 1,10-dicyano substitution restricts the paragon fluxionality of bullvalene to just 14 isomers which isomerize along a single cycle. The restricted fluxionality of 1,10-dicyanobullvalene (DCB) is investigated by means of: (i) Bonding analyses of the isomer structures using the adaptive natural density partitioning (AdNDP). (ii) Quantum dynamical simulations of the isomerizations along the cyclic intrinsic reaction coordinate of the potential energy surface (PES). The PES possesses 14 equivalent potential wells supporting 14 isomers which are separated by 14 equivalent potential barriers supporting 14 transition states. Accordingly, at low temperatures, DCB appears as a hindered molecular rotor, without any delocalization of the wavefunction in the 14 potential wells, without any nuclear spin isomers, and with completely negligible tunneling. These results are compared and found to differ from those for molecular boron rotors. (iii) Born-Oppenheimer molecular dynamics (BOMD) simulations of thermally activated isomerizations. (iv) Calculations of the rate constants in the frame of transition state theory (TST) with reasonable agreement achieved with the BOMD results. (v) Simulations of the equilibration dynamics using rate equations for the isomerizations with TST rate coefficients. Accordingly, in the long-time limit, isomerizations of the 14 isomers, each with Cs symmetry, approach the "14 Cs → C7v" thermally averaged structure. This is a superposition of the 14 equally populated isomer structures with an overall C7v symmetry. By extrapolation, the results for DCB yield working hypotheses for so far un-explored properties e.g. for the equilibration dynamics of C10H10.

Transcriptome and single-cell analysis reveal disulfidptosis-related modification patterns of tumor microenvironment and prognosis in osteosarcoma.

Osteosarcoma (OS) is the most common malignant bone tumor with high pathological heterogeneity. Our study aimed to investigate disulfidptosis-related modification patterns in OS and their relationship with survival outcomes in patients with OS. We analyzed the single-cell-level expression profiles of disulfidptosis-related genes (DSRGs) in both OS microenvironment and OS subclusters, and HMGB1 was found to be crucial for intercellular regulation of OS disulfidptosis. Next, we explored the molecular clusters of OS based on DSRGs and related immune cell infiltration using transcriptome data. Subsequently, the hub genes of disulfidptosis in OS were screened by applying multiple machine models. In vitro and patient experiments validated our results. Three main disulfidptosis-related molecular clusters were defined in OS, and immune infiltration analysis suggested high immune heterogeneity between distinct clusters. The in vitro experiment confirmed decreased cell viability of OS after ACTB silencing and higher expression of ACTB in patients with lower immune scores. Our study systematically revealed the underlying relationship between disulfidptosis and OS at the single-cell level, identified disulfidptosis-related subtypes, and revealed the potential role of ACTB expression in OS disulfidptosis.

Ultrasonic imaging of delamination in thick CFRP laminates using an energy-compensation reverse time migration method.

In ultrasonic reflection method, the precision of defect detection in thick carbon fiber reinforced plastics (CFRP) is compromised by acoustic energy attenuation. An energy-compensation reverse time migration (ECRTM) method is proposed to identify multiple defects accurately. Forward and backward wavefields are formed using the finite element method within an anisotropic acoustic model based on the Christoffel equation and Bond transformation. To enhance the imaging quality of CFRP laminates, a novel cross-correlation imaging condition is introduced to compensate for energy dissipation caused by geometric diffusion and variations of the far-field radiation intensity at the emitter with the propagation direction. Employing ultrasonic detection technology with a multi-element array, numerical and experimental research on defect imaging was conducted, considering delamination with various sizes and positions in a multidirectional CFRP laminate. In comparison to other ultrasonic imaging methods, the near-surface artifacts in RTM images are mitigated by the far-field radiation directivity factor, while the deep information is enhanced by the geometric diffusion compensation factor in the ECRTM images. As a result, the precise position of delamination in CFRP laminates is achievable, demonstrating superior imaging capabilities, especially for deep delamination.

SETDB1 promotes progression through upregulation of SF3B4 expression and regulates the immunity in ovarian cancer.

BACKGROUND: Ovarian cancer (OC) is the most lethal gynecologic malignant tumour. The mechanism promoting OC initiation and progression remains unclear. SET domain bifurcated histone lysine methyltransferase 1(SETDB1) acts as an oncogene in a variety of tumours. This study aims to explore the role of SETDB1 in OC. METHODS: GEO, TCGA, CSIOVDB and CPTAC databases jointly analysed SETDB1 mRNA and protein expression. Effect of SETDB1 expression on the clinical prognosis of OC patients was analysed through online Kaplan‒Meier plotter and CSIOVDB database. Then, the effect of SETDB1 in OC cells progression and mobility was examined using MTT, EdU, colony formation and transwell assay. Additionally, Cistrome DB database was used to visualize the binding of SETDB1 protein and splicing factor 3b subunit 4 (SF3B4) promoter, and dual-luciferase reporter gene assay was performed to confirm the interaction. Finally, bioinformatics analysis was employed to reveal the relationship between SETDB1 and the microenvironment of OC. RESULTS: In the present study, we found that SETDB1 was obviously upregulated in OC and its overexpression predicted poor prognosis of OC patients. Then, we verified that SETDB1 promoted the progression and motility of OC cells in vitro. Knockdown of SETDB1 had the opposite effect. Further research showed that SETDB1 acted as a transcription factor to activate SF3B4 expression. SF3B4 knockdown impaired the effect of SETDB1 to promote the proliferative capacity and motility of OC cells. Finally, the results of bioinformatics analysis confirmed that SETDB1 regulated the immune microenvironment of ovarian cancer. CONCLUSION: SETDB1 promoted ovarian cancer progression by upregulating the expression of SF3B4 and inhibiting the tumour immunity. SETDB1 may be a promising prognostic and therapeutic marker for OC.

4-Octyl itaconate alleviates renal ischemia reperfusion injury by ameliorating endoplasmic reticulum stress via Nrf2 pathway.

Renal ischemia-reperfusion injury (IRI) is a common clinical complication of multiple severe diseases. Owing to its high mortality and the lack of effective treatment, renal IRI is still an intractable problem for clinicians. Itaconate, which is a metabolite of cis-aconitate, can exert anti-inflammatory and antioxidant roles in many diseases. As a derivative of itaconate with high cell membrane permeability, 4-octyl itaconate (4-OI) could provide a protective effect for various diseases. However, the role of 4-OI in renal IRI is still unclear. Herein, we examined whether 4-OI afforded kidney protection through attenuating endoplasmic reticulum stress (ERS) via nuclear factor erythroid-2-related factor 2 (Nrf2) pathway. To observe the effects of 4-OI on alleviating renal pathologic injury, improving renal dysfunction, decreasing inflammatory cytokines, and reducing oxidative stress, we utilized C57BL/6J mice with bilateral renal pedicle clamped and HK-2 cells with hypoxia/reoxygenation (H/R) exposure in our study. In addition, through western blot assay, we found 4-OI ameliorated renal IRI-induced ERS, and activated Nrf2 pathway. Moreover, Nrf2-knockout (KO) mice and Nrf2 knockdown HK-2 cells were used to validate the role of Nrf2 signaling pathway in 4-OI-mediated alleviation of ERS caused by renal IRI. We demonstrated that 4-OI relieved renal injury and suppressed ERS in wild-type mice, while the therapeutic role was not shown in Nrf2-KO mice. Similarly, 4-OI could exert cytoprotective effect and inhibit ERS in HK-2 cells after H/R, but not in Nrf2 knockdown cells. Our in vivo and in vitro studies revealed that 4-OI protected renal IRI through attenuating ERS via Nrf2 pathway.

Multiscale levels CO2 decouple reinforcement in China.

Decoupling economic growth from CO2 emissions is imperative for China. Meanwhile, establishing a consistent and comprehensive decoupling inventory that includes national (N), regional and provincial (RP), and city and county (CC) levels is essential for further policy formulation. This research aims to investigate the decoupling status using the "N-RP-CC" approach while considering changes in decoupling trends at the different levels. A combination of the Tapio decoupling model and cluster analysis is employed to study the decoupling's spatiotemporal characteristics and trends. The study first calculates the decoupling value for "national, 7; regions, 30; provinces, 1501 CCs" in China, 2006-2017. The results show that there continues to be an improvement in the decoupling trend at the national level. Conversely, the regional scale exhibits a more vulnerable decoupling trend compared to the national level, with weak and extended negative decoupling observed in northeastern and northern China. Moreover, provincial heterogeneities are increasingly evident, with poor decoupling statuses appearing in Jilin, Heilongjiang, Liaoning, and Xinjiang, as well as many central provinces. Additionally, although more than half of CCs exhibit weak decoupling during most years, seven different states of decoupling were also identified during the time frame. These findings further indicate that spatiotemporal heterogeneities extend beyond RP scales within CCs. Taking the Yangtze River as a boundary line reveals a severe situation in northern areas along with rapid development trends observed in southern regions. Finally, we clustered 1414 CCs based on their industrial proportions for 2017 which further highlights increasingly prominent heterogeneities that should be carefully considered. Based on these findings, policy recommendations such as spatial organization and optimization and technique investment are proposed to achieve CO2 emission decoupling under the N-RP-CC levels.

Effect of different metastasis patterns on the prognosis of patients with stage III high-grade serous ovarian cancer.

To investigate the effect of different metastatic patterns of stage III high-grade serous ovarian cancer on the patient prognosis. The clinical data of 134 patients with Stage III, high-grade serous ovarian cancer diagnosed in The Affiliated Hospital of Qingdao University from January 2018 to April 2020 were retrospectively collected, and the patients were grouped according to metastasis mode. Patients with simple lymph node metastasis (SLNM) were included in the SLNM group, and patients with simple abdominal implantation alone and patients with abdominal metastasis combined with lymph node metastasis were all in the abdominal metastasis (AM) group. The prognosis of the two groups was analyzed. Of the 134 enrolled patients, complete datasets from 128 were successfully collected. There were 20 cases of SLNM (15.63%) and 108 cases of AM (84.37%). Initial CA125, initial HE4, and whether neoadjuvant chemotherapy was used were compared between the two groups (P < 0.05). According to the chemotherapy results, patients was divided into two groups: chemotherapy remission and uncontrolled, including 111 patients with chemotherapy remission and 17 patients with uncontrolled chemotherapy. According to the criteria of relapse after complete completion of chemotherapy and clinical remission, 91 cases relapsed, 20 cases did not relapse, of which 78 cases were platinum-sensitive, and 13 were platinum-resistant relapses. There were 4 recurrence cases in SLNM group (4.40%) and 87 recurrence cases (95.60%) in AM group (P < 0.05). The recurrence sites of 91 patients were analyzed, including 52 cases (57.14%) in the peritoneum, 11 cases (12.09%) in distant regions, 9 cases (9.89%) in lymph nodes, 19 cases (20.88%) in the peritoneum and lymph nodes. Significant differences were noted in the two groups' peritoneum, lymph node, and distance (P < 0.05). The two groups had significant differences in progression-free survival, overall survival, and 3-year survival (all P < 0.05). Initial HE4 levels, chemotherapy sensitivity, and SLNM are independent prognostic factors for Stage III high-grade serous ovarian cancer patients. Initial HE4 level < 233.7 pmol/l and chemotherapy sensitivity were protective factors, indicating a good prognosis. Patients in the SLNM group had lower initial CA125 and HE4 levels and higher survival rates. Initial HE4 levels and chemotherapy sensitivity are independent factors affecting prognosis in Stage III high-grade serous ovarian cancer patients.

A review on guided-ultrasonic-wave-based structural health monitoring: From fundamental theory to machine learning techniques.

The development of structural health monitoring (SHM) techniques is of great importance to improve the structural efficiency and safety. With advantages of long propagation distances, high damage sensitivity, and economic feasibility, guided-ultrasonic-wave-based SHM is recognized as one of the most promising technologies for large-scale engineering structures. However, the propagation characteristics of guided ultrasonic waves in in-service engineering structures are highly complex, which results in difficulties in developing precise and efficient signal feature mining methods. The damage identification efficiency and reliability of existing guided ultrasonic wave methods cannot meet engineering requirements. With the development of machine learning (ML), numerous researchers have proposed improved ML methods that can be incorporated into guided ultrasonic wave diagnostic techniques for SHM of actual engineering structures. To highlight their contributions, this paper provides a state-of-the-art overview of the guided-wave-based SHM techniques enabled by ML methods. Accordingly, multiple stages required for ML-based guided ultrasonic wave techniques are discussed, including guided ultrasonic wave propagation modeling, guided ultrasonic wave data acquisition, wave signal pre-processing, guided wave data-based ML modeling, and physics-based ML modeling. By placing ML methods in the context of the guided-wave-based SHM for actual engineering structures, this paper also provides insights into future prospects and research strategies.

The Effect of Trichoderma harzianum Hypovirus 1 (ThHV1) and Its Defective RNA ThHV1-S on the Antifungal Activity and Metabolome of Trichoderma koningiopsis T-51.

Mycoviruses widely exist in filamentous fungi and sometimes cause phenotypic changes in hosts. Trichoderma harzianum hypovirus 1 (ThHV1) and its defective RNA ThHV1-S were found in T. harzianum and exhibited high transmissibility. In our previous study, ThHV1 and ThHV1-S were transferred to an excellent biological control agent T. koningiopsis T-51 to form a derivative strain 51-13. In this study, we assessed the metabolic changes in strain 51-13 and antifungal activity of its culture filtrate (CF) and volatile organic compounds (VOCs). The antifungal activity of CF and VOCs of T-51 and 51-13 was different. Compared with the CF of T-51, that of 51-13 exhibited high inhibitory activity against B. cinerea, Sclerotinia sclerotiorum, and Stagonosporopsis cucurbitacearum but low inhibitory activity against Leptosphaeria biglobosa and Villosiclava virens. The VOCs of 51-13 exhibited high inhibitory activity against F. oxysporum but low inhibitory activity against B. cinerea. The transcriptomes of T-51 and 51-13 were compared; 5531 differentially expressed genes (DEGs) were identified in 51-13 with 2904 up- and 2627 downregulated genes. In KEGG enrichment analysis, 1127 DEGs related to metabolic pathways (57.53%) and 396 DEGs related to biosynthesis of secondary metabolites (20.21%) were clearly enriched. From the CF of T-51 and 51-13, 134 differential secondary metabolites (DSMs) were detected between T-51 and 51-13 with 39 up- and 95 downregulated metabolites. From these, 13 upregulated metabolites were selected to test their antifungal activity against B. cinerea. Among them, indole-3-lactic acid and p-coumaric acid methyl ester (MeCA) exhibited strong antifungal activity. The IC50 of MeCA was 657.35 µM and four genes possibly related to the synthesis of MeCA exhibited higher expression in 51-13 than in T-51. This study revealed the mechanism underlying the increase in antifungal activity of T-51 because of the mycovirus and provided novel insights in fungal engineering to obtain bioactive metabolites via mycoviruses.

Radiomics nomogram for preoperative differentiation of early-stage serous borderline ovarian tumors and serous malignant ovarian tumors.

Objectives: This study aimed to construct a radiomics nomogram and validate its performance in the preoperative differentiation between early-stage (I and II) serous borderline ovarian tumors (SBOTs) and serous malignant ovarian tumors (SMOTs). Methods: Data were collected from 80 patients with early-stage SBOTs and 102 with early-stage SMOTs (training set: n = 127; validation set: n = 55). Univariate and multivariate analyses were performed to identify the independent clinicoradiological factors. A radiomics signature model was constructed using radiomics features extracted from multidetector computed tomography images of the venous phase, in which the least absolute shrinkage and selection operator regression was employed to lessen the dimensionality of the data and choose the radiomics features. A nomogram model was established by combining independent clinicoradiological factors with the radiomics signature. The performance of nomogram calibration, discrimination, and clinical usefulness was evaluated using training and validation sets. Results: In terms of clinicoradiological characteristics, age (p = 0.001), the diameter of the solid component (p = 0.009), and human epididymis protein 4 level (p < 0.001) were identified as the independent risk factors of SMOT, for which the area under the curves (AUCs) were calculated to be 0.850 and 0.836 in the training and validation sets, respectively. Nine features were finally selected to construct the radiomics signature model, which exhibited AUCs of 0.879 and 0.826 for the training and validation sets, respectively. The nomogram model demonstrated considerable calibration and discrimination with AUCs of 0.940 and 0.909 for the training and validation sets, respectively. The nomogram model displayed more prominent clinical usefulness than the clinicoradiological and radiomics signature models according to the decision curve analysis. Conclusions: The nomogram model can be employed as an individualized preoperative non-invasive tool for differentiating early-stage SBOTs from SMOTs.

Changes in Fruit Quality Phytochemicals of Late-Mature Peach 'Yonglian No.1' during Storage.

In this study, the changes in quality parameters and sensory-influencing parameters from the peel, red flesh, and white flesh of 'Yonglian No.1' peach fruits were analyzed during cold storage. The results indicated that the contents of total soluble solids (TSS), soluble sugar, organic acid, vitamin C, total anthocyanin, phenol, and flavonoids, as well as the good fruit rate varied depending on the storage stages and storage treatments. The peach fruits in MAP stored for 50 days had favorable exterior qualities, a good fruit rate of 100%, and a higher content of total soluble solids (TSS) at 12.6%. MAP was significantly effective at maintaining fruit firmness, the content of TSS, soluble sugar, organic acid, vitamin C, total anthocyanin, phenol, and flavonoids. Among the derivatives of anthocyanin, both cyanidin and pelargonidin were found in the peel, with a content of 33.45 mg/kg FW and 1.82 mg/kg FW, respectively. However, cyanidin was detected in the flesh with a content of 40.42 mg/kg FW. In the present work, the differences regarding phytochemical profiles and physical properties were mainly correlated with the storage stages and storage treatments of peach fruit. 'Yonglian No.1' had higher levels of health-promoting compounds during storage and maintained favorable quality.

Impact of intergenerational support and medical expenditures on depression: Evidence from rural older adults in China.

Objective: Globally, depression has become a major health issue among older adults, who experience poor physical health and high medical expenditures. In Asian countries, older adults are greatly dependent on their children. This study assessed the impact of different types of intergenerational support and medical expenditures on depression among older adults in rural China. Method: A three-phase balanced panel was constructed based on data from 1,838 rural older adults with comparable scores on the Center for Epidemiologic Studies Depression Scale (CES-D) from the China Family Panel Studies in 2012, 2016, and 2018. A fixed-effects model was used to analyze the impact of intergenerational support and medical expenditures on CES-D score and of intergenerational support on medical expenditures. The propensity score-matching model was used to test the regression results' robustness. Results: The findings were as follows. First, different types of intergenerational support had a heterogeneous impact on depression among rural older adults. Emotional support had a significantly negative impact on CES-D score, although too much care-based support had a positive impact on CES-D score. Low-level economic support had no significant effect on CES-D score. Second, medical expenditures impacted depression; among these, non-inpatient medical expenditure had a significant and positive impact on CES-D score. Third, CES-D scores among rural older adults were associated with chronic diseases and per capita family income. Fourth, care-based support was associated with reduced non-inpatient medical expenditures, and the sub-sample regression results indicated that the impact was significant for older adults with no chronic diseases and those younger than 75 years. Conclusion: Intergenerational emotional support and non-inpatient medical expenditures directly affected rural older adults' CES-D scores. The mediating role of medical expenditures between intergenerational support and CES-D score was not significant. Measures should be taken to encourage intergenerational emotional support and reduce the pressure on children's economic and care-based support. Further, the medical insurance reimbursement policy, as formal support, should be improved to alleviate depression among rural older adults when children's support is limited.

Contact Characteristics and Tribological Properties of the Weaving Surface of Mn-Cu and Fe-Zn Damping Alloys.

In this paper, laser texturing is performed on the surface of Mn-Cu and Fe-Zn damping alloys and the tribological properties of the samples with various surface weaves under dry-sliding conditions are investigated. The results show that the surface weave parameters affect the size of the contact surface and change the number of micro-convex bodies at the contact interface. This leads to changes in the tangential damping of the contact and further affects the magnitude of the friction coefficient. Additionally, the damping properties significantly affect the wear mechanism and make it more prone to adhesive wear.

Imaging a defect in layered media with different shaped interfaces using reverse time migration without velocity model known a priori.

In this work, the highly accurate image of a defect in the layered media using a reverse time migration (RTM) is obtained without priori information of the interface geometry and acoustic velocity of the lower medium. The interface of layered media is reconstructed by RTM, and its profile is determined using the reconstructed image within the range of -6 to 0 dB. At the assumed acoustic velocity of the lower medium, the minimum variance of the possible position distribution of a defect is evaluated to be an acoustic velocity of the lower medium by processing the travel times of the defect scattered echoes. The velocity model of the layered media is reconstructed by the mapped interface and the calibrated acoustic velocity of the lower medium, and a defect in the layered media is imaged by RTM. The proposed method is verified by utilizing the silicone rubber-water layered media with horizontal, titled, and circular arc interfaces. The obtained results for the interface geometry, acoustic velocity of the lower medium, and location of defect are consistent with the actual values. Therefore, a defect in the layered media can be accurately located and imaged without the velocity model of layered media known a priori via the RTM method.

Biological Control and Plant Growth Promotion by Volatile Organic Compounds of Trichoderma koningiopsis T-51.

Trichoderma spp. are widely used in plant disease control and growth promotion due to their high efficacy and multiple biocontrol mechanisms. Trichoderma koningiopsis T-51 is an effective biocontrol agent against gray mold disease by direct contact. However, the indirect physical contact biocontrol potential of Trichoderma spp. is not clear. In this study, the volatile organic compounds (VOCs) produced by T-51 showed high inhibitory activity against plant pathogenic fungi Botrytis cinerea and Fusarium oxysporum. The percentage of B. cinerea and F. oxysporum mycelial growth inhibition by T-51 VOCs was 73.78% and 43.68%, respectively. In both B. cinerea and F. oxysporum, conidial germination was delayed, and germ tube elongation was suppressed when exposed to T-51 VOCs, and the final conidial germination rate of B. cinerea decreased significantly after T-51 treatment. The VOCs from T-51 reduced the Botrytis fruit rot of tomato compared with that noted when using the control. Moreover, the T-51 VOCs significantly increased the size and weight of Arabidopsis thaliana seedlings. Twenty-four possible compounds, which were identified as alkenes, alkanes, and esters, were detected in VOCs of T-51. These results indicate that T. koningiopsis T-51 can exert biological control by integrating actions to suppress plant disease and promote plant growth.

Cloning and Expression Analysis of Flavonoid 3', 5'-Hydroxylase Gene from Brunfelsia acuminata.

The full-length cDNA sequence of F3'5'H gene from the Brunfelsia acuminata was obtained by RT-PCR and RACE, whose GenBank accession number is JQ678765. The sequence contains a 1521 bp open reading frame, 120 bp 5'UTR and 61 bp 3'UTR, encoding a total of 506 amino acids. The molecular mass of the predicted protein is 56.47 kDa with an estimated pI of 8.78, respectively. Sequence alignment showed that the amino acid sequence of F3'5'H was 91%, 87% and 84% with that of Petunia × hybrida, Nierembergia sp., Solanum tuberosum, respectively. Real-time quantitative PCR analysis showed that the expression of F3'5'H gene was different in petals of different days, which was the highest expression level on day 0 and significantly higher than other days. The results indicated that F3'5'H might play key role in flower color regulation and provide a theoretical reference for blue flower molecular breeding.

Bailing Capsule combined with α-ketoacid tablets for stage 3 chronic kidney disease: Protocol of a double-blinded, randomized, controlled trial.

BACKGROUND: Chronic kidney disease (CKD) is a progressive and irreversible loss of kidney function. After stage 3, there will be increased risks of hypertension, heart failure, bone disease, anemia, gastrointestinal symptoms, and progression to end-stage kidney failure without proper intervention and treatment. Compound α-ketoacid tablets (KA) administration plays an important role in clinical CKD adjunctive therapy for patients with restricted protein intake. Bailing Capsule (BC), a commonly used Chinese patent medicine for renal diseases, could regulate human immune function, repair renal tubular epithelial cells, prevent renal tubular atrophy, and reduce kidney damage to improve renal function. In this study, we try to conduct a double-blinded, randomized, controlled trial to observe the efficacy and safety of BC combined with KA in treating patients with stage 3 CKD. METHODS: This is a double-blinded, randomized, controlled trial. Patients will be randomly divided into treatment group (BC and KT) and control group (BC-simulation and KT) in a 1:1 ratio according to random number table. The treatment course will be 8 weeks, and the changes of subjective symptoms, patient global assessment (PGA) scale, serum creatinine, cystatin C, and estimated glomerular filtration rate, all related adverse events, vital sign measurements, and physical examinations will be recorded. SPSS 21.0 will be used for data analysis. CONCLUSIONS: The results will show whether BC combined with KA could alleviate the symptoms of fatigue, anorexia, halitosis, nausea, itching, and edema, improve kidney function in patients with CKD at stage 3. TRIAL REGISTRATION: OSF Registration number: DOI 10.17605/OSF.IO/24AJ7.

Evaluation of Ovarian Tumors with Multidetector Computed Tomography and Tumor Markers: Differentiation of Stage I Serous Borderline Tumors and Stage I Serous Malignant Tumors Presenting as Solid-Cystic Mass.

BACKGROUND The aim of this study was to determine multidetector computed tomography (MDCT) features and tumor markers for differentiating stage I serous borderline ovarian tumors (SBOTs) from stage I serous malignant ovarian tumors (SMOTs). MATERIAL AND METHODS In total, 48 patients with stage I SBOTs and 54 patients with stage I SMOTs who underwent MDCT and tumor markers analysis were analyzed. MDCT features included location, shape, margins, texture, papillary projections, vascular abnormalities, size, and attenuation value. Tumor markers included serum cancer antigen 125 (CA125), carbohydrate antigen 19-9 (CA19-9), carcinoembryonic antigen (CEA), and human epididymis protein 4 (HE4). Parameters of clinical characteristic, MDCT features, and tumor markers were compared using a chi-square test and Mann-Whitney U tests. A binary logistic regression analysis was performed to detect predictors for SMOTs. A receiver operating characteristic (ROC) curve analysis was used to assess the potential diagnostic value of the quantitative parameters. Kappa and intraclass correlation coefficients were used to evaluate interobserver reproducibility for MDCT features. RESULTS Median ages between patients with SBOTs and SMOTs were significantly different. Compared with SBOTs, vascular abnormalities were significantly more common in SMOTs. CA125, HE4, the maximum thickness of the wall, the maximum thickness of the septa, and the maximum diameter of the solid portions were significantly higher in patients with SMOTs. A binary logistic regression analysis revealed that age, vascular abnormalities, and the maximum diameter of the solid portion were independent factors of SMOTs. ROC analysis was used to assess the potential diagnostic value for predicting SMOTs. Moderate or good interobserver reproducibility for MDCT features were identified. CONCLUSIONS Age, vascular abnormalities, and the maximum diameter of the solid portion were independent factors for differentiating SBOTs from SMOTs. The combined analysis of age, vascular abnormalities, and the maximum diameter of the solid portion may allow better differentiation between SBOTs and SMOTs.

C-Myc-activated long non-coding RNA PVT1 enhances the proliferation of cervical cancer cells by sponging miR-486-3p.

Cervical cancer is one of the most prevalent gynecological malignancies. Although the functions of long non-coding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) and c-Myc in tumorigenesis have been acknowledged, the roles of c-Myc and lncRNA-PVT1 in the proliferation of cervical cancer are still unclear. Our study is designed to demonstrate the regulatory network involving c-Myc and lncRNA-PVT1 in cervical cancer. Quantitative real-time PCR and western blot assays were performed in our research to estimate the expression levels of RNA and proteins. CCK8 assays were applied to demonstrate the viability of HeLa and SiHa cells. Immunofluorescence assay was then used to investigate the co-localization of lncRNA-PVT1 and miR-486-3p. Binding of c-Myc to the promoter region of PVT1 was identified by ChIP-assay. Functionally, upregulation of lncRNA-PVT1 enhanced the proliferation and viability of cervical cancer cells. Mechanistically, lncRNA-PVT1 sponged miR-486-3p and released its repression of extracellular matrix protein 1. Besides, c-Myc functioned as an activator of lncRNA-PVT1 and upregulated its expression by binding to the promoter of PVT1 in cervical cancer cells. lncRNA-PVT1 was upregulated by c-Myc and thus enhanced the proliferation of cervical cancer cells by sponging miR-486-3p.

SiRNA-Mediated RRM2 Gene Silencing Combined with Cisplatin in the Treatment of Epithelial Ovarian Cancer In Vivo: An Experimental Study of Nude Mice.

Introduction: We aimed to explore small interfering (si)RNA silencing of ribonucleotide reductase M2 (RRM2) gene combined with cisplatin for the treatment of human ovarian cancer in nude mice models of subcutaneous transplantation of tumor cells. Methods: After conventional cultivation of human ovarian cancer cell line SKOV3 in vitro, SKOV3 cells were injected into the right back of nude mice by subcutaneous injection to establish the subcutaneous tumor models. Twenty-four tumor-burdened rats were randomly divided into four groups (n=6): siRNA group, siRNA in combination with cisplatin group, cisplatin group, and control group. Intraperitoneal injection of cisplatin and subcutaneous injection of siRNA were performed weekly. Tumor volume was measured, and tumor growth inhibition rate was calculated. RRM2 expression at the mRNA and protein levels was detected by reverse transcription-polymerase chain reaction and immunohistochemistry. Results: In the siRNA group, the tumor volume and tumor growth inhibition rate were 249.60±20.46 mm³ and 36.39%, respectively. The tumor growth inhibition rate and tumor volume were significantly different between the siRNA and control groups (p<0.05). In the cisplatin group, the tumor volume and tumor growth inhibition rate were 249.86±12.46 mm³ and 41.10%, respectively. The tumor growth inhibition rate and tumor volume were significantly different between the cisplatin and control groups (p<0.05). In the siRNA + cisplatin group, the tumor volume reduced to 180.84±16.25 mm³ and the tumor growth inhibition rate was increased to 64.33%, which were significantly different compared with the control group (p<0.01). Significant downregulation of RRM2 mRNA and protein expression in the tumor tissues was detected by reverse transcription polymerase chain reaction and immunohistochemistry assay (p<0.05). Discussion: siRNA alone or combined with cisplatin can effectively inhibit the growth of human ovarian cancer in nude mice models of subcutaneous transplantation of tumor cells. RRM2 gene silencing may be a potential treatment regimen for ovarian cancer in future.