Alternative splicing in ovarian cancer.

Ovarian cancer is the second leading cause of gynecologic cancer death worldwide, with only 20% of cases detected early due to its elusive nature, limiting successful treatment. Most deaths occur from the disease progressing to advanced stages. Despite advances in chemo- and immunotherapy, the 5-year survival remains below 50% due to high recurrence and chemoresistance. Therefore, leveraging new research perspectives to understand molecular signatures and identify novel therapeutic targets is crucial for improving the clinical outcomes of ovarian cancer. Alternative splicing, a fundamental mechanism of post-transcriptional gene regulation, significantly contributes to heightened genomic complexity and protein diversity. Increased awareness has emerged about the multifaceted roles of alternative splicing in ovarian cancer, including cell proliferation, metastasis, apoptosis, immune evasion, and chemoresistance. We begin with an overview of altered splicing machinery, highlighting increased expression of spliceosome components and associated splicing factors like BUD31, SF3B4, and CTNNBL1, and their relationships to ovarian cancer. Next, we summarize the impact of specific variants of CD44, ECM1, and KAI1 on tumorigenesis and drug resistance through diverse mechanisms. Recent genomic and bioinformatics advances have enhanced our understanding. By incorporating data from The Cancer Genome Atlas RNA-seq, along with clinical information, a series of prognostic models have been developed, which provided deeper insights into how the splicing influences prognosis, overall survival, the immune microenvironment, and drug sensitivity and resistance in ovarian cancer patients. Notably, novel splicing events, such as PIGV|1299|AP and FLT3LG|50,941|AP, have been identified in multiple prognostic models and are associated with poorer and improved prognosis, respectively. These novel splicing variants warrant further functional characterization to unlock the underlying molecular mechanisms. Additionally, experimental evidence has underscored the potential therapeutic utility of targeting alternative splicing events, exemplified by the observation that knockdown of splicing factor BUD31 or antisense oligonucleotide-induced BCL2L12 exon skipping promotes apoptosis of ovarian cancer cells. In clinical settings, bevacizumab, a humanized monoclonal antibody that specifically targets the VEGF-A isoform, has demonstrated beneficial effects in the treatment of patients with advanced epithelial ovarian cancer. In conclusion, this review constitutes the first comprehensive and detailed exposition of the intricate interplay between alternative splicing and ovarian cancer, underscoring the significance of alternative splicing events as pivotal determinants in cancer biology and as promising avenues for future diagnostic and therapeutic intervention.

Optimized dielectric mirror coating designs for quasi-harmonic cavity resonance.

High-finesse optical cavities have a wide range of applications, some of which are bichromatic. The successful operation of high-finesse bichromatic cavities can demand careful control on the temperature dependence of the wavelength-dependent reflection phase from the dielectric mirror coatings that constitute the optical cavity. We present dielectric coating designs that are optimized for minimal differential change in the reflection phase between a quasi-second-harmonic field and its fundamental field under temperature changes. These designs guarantee cavity resonance at a wavelength of interest via the control of its quasi-harmonic field. The proposed coating designs are additionally examined for their sensitivity to manufacturing errors in the coating layer thickness with promising results.

Temperature effects in narrow-linewidth optical cavity control with a surrogate quasi-second-harmonic field.

Fabry-Perot cavities are widely used in precision interferometric applications. Various techniques have been developed to achieve the resonance condition via the direct interrogation of the cavity with the main laser field of interest. Some use cases, however, require a surrogate field for cavity control. In this study, we construct a bichromatic cavity to study the surrogate control approach, where the main and the surrogate fields are related by the second-harmonic generation with nonlinear optics. We experimentally verify the temperature dependence of the differential reflection phase of a dielectric coating design optimized for the surrogate control approach of the optical cavities of the light-shining-through-a-wall experiment Any Light Particle Search II and develop a comprehensive cavity model for quasi-second-harmonic resonances that considers also other important factors, such as the Gouy phase shift, for a detailed analysis of the surrogate control approach.

[Effect and mechanism of Gusong Qianggu Decoction on reducing bone loss in ovariectomized mice by targeting endoplasmic reticulum stress-induced apoptosis of osteocytes].

This study aims to investigate the role and mechanism of Gusong Qianggu Decoction(GSQG) in attenuating bone loss in ovariectomized mice by targeting the endoplasmic reticulum stress(ERS)-induced apoptosis of osteocytes. After the modeling of osteoporosis in mice with bilateral ovary removal(OVX), 60 mice were randomized by the random number method into six groups: sham,model, low-, medium-, and high-dose GSQG(GSQG-L, GSQG-M, and GSQG-H, respectively), and estradiol(E_2), with 10 mice in each group. The mice in each group were administrated with corresponding drugs by gavage one month after surgery and the administration lasted for 3 months. Enzyme-linked immunosorbent assay(ELISA) was employed to determine the serum levels of osteocalcin(OCN), procollagen type Ⅰ N-terminal propeptide(PINP), carboxy-terminal cross-linked telopeptide of type Ⅰ collagen(CTX),and anti-tartarte acid phosphatase 5b(TRAcP-5b). Micro-CT was employed to observe the changes in bone microstructure of the distal femur. Hematoxylin-eosin(HE) staining was employed to observe the morphology of the bone tissue. RT-qPCR was conducted to determine the m RNA levels of tibial stem osteogenesis-associated genes [type Ⅰ collagen(Col-Ⅰ), alkaline phosphatase(ALP), Runtrelated transcription factor-2(Runx2), bone sialoprotein(BSP), and OCN] and bone-breaking related genes [tartrate-resistant acid phosphatase(TRAP), nuclear factor-activated T cell 1(NFATc1), and cathepsin K(CATK)]. TUNEL staining and immunohistochemistry were employed to detect the apoptosis of osteoblasts. Western blot was employed to measure the expression of ERS-related proteins glucose-regulated protein 78( Grp78), protein kinase RNA-like endoplasmic reticulum kinase( PERK), phosphorylated PERK(p-PERK),eukaryotic translation initiation factor 2 alpha(eIF2α), phosphorylated e IF2α(p-eIF2α), inositol-requiring enzyme 1 alpha(IRE1α), phosphorylated IRE1α(p-IRE1α), and activating transcription factor 6(ATF6) in the proximal tibial bone tissue. The results showed that GSQG significantly recovered the levels of OCN, PINP, TRAc P-5b, and CTX in the serum of ovariectomized mice, and Micro-CT showed that GSQG improved the bone microstructure of distal femur in a dose-dependent manner. Compared with the model group, GSQG widened and increased the bone trabeculae, restored the reticular structure with neat arrangement and enlarged interstitial gaps, and reduced the number of TUNEL-positive cells(P<0. 05, P<0. 01). Furthermore, GSQG down-regulated the expression levels of cysteine aspartate protease-3( caspase-3) and factor Bcl-2-associated X protein( Bax)(P< 0. 05,P<0. 01) and up-regulated the expression level of Bcl-2(P<0. 05, P<0. 01). The GSQG groups showed up-regulated m RNA levels of Col-Ⅰ, ALP, Runx2, BSP, and OCN(P< 0. 01) and down-regulated m RNA levels of TRAP, NFATc1, and CATK(P< 0. 05,P<0. 01). In addition, GSQG, especially GSQG-H, down-regulated the protein levels of Grp78, p-PERK, p-eIF2, p-IRE1α, and ATF6(P< 0. 05, P< 0. 01). In conclusion, GSQG can inhibit the apoptosis of osteocytes by inhibiting the Grp78/PERK/e IF2α/IRE1α/ATF6 signaling pathway in the proximal tibia tissue, thus reducing bone loss in ovariectomized mice.

Optics mounting and alignment for the central optical bench of the dual cavity enhanced light-shining-through-a-wall experiment ALPS II.

Any Light Particle Search II (ALPS II) is a light-shining-through-a-wall experiment seeking axion-like particles. ALPS II will feature two 120 m long linear optical cavities that are separated by a wall and support the same photon mode. The central optical bench at the core of the experiment will be equipped with a light-tight shutter and two planar mirrors for the cavities. We show that the mounting concept for ALPS II provides sufficient angular stability and verify that a simple autocollimator assisted alignment procedure for crucial components of the ALPS II optical cavities can lead to the required overlap of the cavity eigenmodes. Furthermore, we show that mounted quadrant photodiodes added to the optical bench can have sufficient stability to maintain this overlap even without a clear line of sight between the two optical cavities.

Local intra-articular injection of resveratrol delays cartilage degeneration in C57BL/6 mice by inducing autophagy via AMPK/mTOR pathway.

Autophagy is an essential cellular homeostasis mechanism that was found to be compromised in aging and osteoarthritis (OA) cartilage. Previous studies showed that resveratrol can effectively regulate autophagy in other cells. The purpose of this study was to determine whether the chondroprotective effect of resveratrol was related to chondrocyte autophagy and to elucidate underlying mechanisms. OA model was induced by destabilization of the medial meniscus (DMM) in 10-week-old male mice. OA mice were treated with resveratrol with/without 3-MA for 8 weeks beginning 4 weeks after surgery. The local intra-articular injection of resveratrol delayed articular cartilage degradation in DMM-induced OA by OARSI scoring systems and Safranin O-fast green. Resveratrol treatment increased Unc-51-like kinase1, Beclin1, microtubule-associated protein light chain 3, hypoxia inducible factor-1α, phosphorylated AMPK, collagen-2A1, Aggrecan expressions, but decreased hypoxia inducible factor-2α, phosphorylated mTOR, matrix metalloproteinases13 and a disintegrin and metalloproteinase with thrombospondin motifs 5 expressions. The effects of resveratrol were obviously blunted by 3-MA except HIF and AMPK. These findings indicate that resveratrol intra-articular injection delayed articular cartilage degeneration and promoted chondrocyte autophagy in an experimental model of surgical DMM-induced OA, in part via balancing HIF-1α and HIF-2α expressions and thereby regulating AMPK/mTOR signaling pathway.

Coherently combined master oscillator fiber power amplifiers for Advanced Virgo.

Stable low-noise high-power lasers are indispensable in advancing the strain sensitivity of interferometric gravitational wave detectors. Advanced LIGO and Advanced Virgo are currently under commissioning and require about 200 W of single-frequency laser power, while the future detector design may require up to the order of 500 W. In this Letter, we present the design and, to the best of our knowledge, the first experimental demonstration of the laser system for Advanced Virgo that is based on coherently combined fiber laser amplifiers. We show the long-term performance of two 40 W fiber laser amplifiers, as well as their characterization in terms of beam quality, power noise, phase noise, and beam pointing. Moreover, a simple and compact setup utilizing fibered modulators and actuators for the coherent beam combination of these two fiber laser amplifiers is reported. A combination efficiency of about 96% was achieved, and no spurious noise was observed.

[Total ginsenosides fought against right ventricular hypertrophy through inhibiting calcineurin signal pathway].

OBJECTIVE: To observe the effect of total ginsenosides (TG) on monocrotaline (MCT) induced right ventricular hypertrophy rats, and to explore its correlation with calcineurin (CaN) pathway. METHODS: Fifty male Sprague Dawley rats were randomly divided into the normal control group, the MCT model group, and the low, middle, high dose TG treatment groups, 10 in each group. All medication was performed by peritoneal injection for 18 days. Right ventricular peak systolic pressure (RVSP), right ventricular hypertrophy index (RVHI), and right ventricular weight/body weight (RVW/BW) were measured. Intracellular free calcium concentrations were measured by Ca2+ fluorescence indicator Fura2/AM. The atrial natriuretic factor (ANF) and CaN mRNA expression of the myocardial tissue were quantitatively analyzed by Real-time PCR. The protein expression of CaN was detected by Western blot. RESULTS: Compared with the MCT model group, preventive treatment of TG at the 3 doses could significantly reduce RVSP, RVHI, RVW/BW, and ANF mRNA expression, and decrease Ca2+ concentration in myocardial cells, CaN mRNA and protein expression in the myocardial tissue. CONCLUSION: TG could obviously improve MCT-induced right ventricular hypertrophy, which was possibly achieved through suppressing MCT-activated CaN signal transduction.

[Effect of xuebijing injection on perioperative coagulation function and inflammatory reaction in senile patients receiving total hip arthroplasty].

OBJECTIVE: To observe the effect of xuebijing Injection (XI) on perioperative coagulation and inflammatory reaction in senile patients receiving total hip arthroplasty (THA). METHODS: Totally eighty patients receiving THA at Luoyang Orthopedics Hospital, 65 to 85 years old, were randomly assigned to the control group (40 cases) and the treatment group (40 cases). All patients received routine perioperative therapies. Those in the treatment group received XI (adding 50 mL XI in 100 mL normal saline, 30 min each time). XI was continually injected after THA, twice daily for 3 successive days. Blood samples were harvested on the morning of the 2nd admission day (TO), immediately after operation (T1), on the morning of the 3rd day after operation (T3), and on the morning of the 5th day after operation (T4) to detect prothrombin time (PT), thrombin time (TT), activated partial thromboplastin time (APTT), levels of FIB and D-dimer (D-D), changes of white blood cell (WBC), neutrophils (N), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and IL-6. Complications of surgery were compared between the two groups. RESULTS: There was no statistical difference in operation time, intraoperative blood loss, and blood transfusion between the two groups (P >0.05). Compared with TO in the same group, WBC, N, CRP, ESR, IL-6, PT, TT, and D-D all increased in the control group at T1-T4 (P < 0.05); APTT increased at T1-T2 (P <0.05); FIB increased at T1-T3 (P <0.05). WBC, N, IL-6, PT, and D-D all increased in the treatment group at T1-T3 (P <0.05); CRP and ESR increased at T1-T4 (P < 0.05); TT increased at T1-T2 (P <0.05); APTT and FIB increased at T1 (P <0.05). Compared with the control group at the same time period, WBC, N, CRP, and IL-6 all decreased in the treatment group at T1-T4 (P <0.05), ESR decreased at T3-T4 (P <0.05); PT and TT decreased at T1-T3 (P <0.05); FIB and D-D decreased at T2-T4 (P<0.05). The occurrence of each complication was significantly lower in the treatment groups than in the control group. CONCLUSION: XI could improve the perioperative high coagulation state of senile THA patients, inhibit inflammatory reactions, and reduce complications.

Intra-articular administration of PLGA resveratrol sustained-release nanoparticles attenuates the development of rat osteoarthritis.

Our previous studies have confirmed that resveratrol (RSV) can prevent the development of osteoarthritis through a variety of mechanisms, such as apoptosis inhibition, autophagy induction and SIRT 1 activation. However, the pharmaceutical application of RSV is mainly limited by its low bioavailability. Here, we designed and synthesized RSV-loaded poly (D, l-lactide-coglycolide acid) (PLGA)-nanoparticles (NPs). The average particle size, polydispersity index and positive charge of RSV-loaded PLGA NPs were 50.40 nm, 0.217 and 12.57 mV, respectively. These nanoparticles had marked encapsulation efficiency (92.35 %) and drug loading (15.1 %) for RSV. It was found that RSV-loaded PLGA NPs not only inhibited the apoptosis of chondrocytes induced by IL-1, but also rescued GAG loss in vitro. Pharmacokinetic data showed that RSV-loaded PLGA NPs demonstrated a significantly profound and prolonged concentration profile in joint tissues, with quantifiable RSV concentrations over 35 days. The therapeutic effects of RSV-loaded PLGA NPs were then examined in rat osteoarthritis models. In vitro magnetic resonance imaging results showed that RSV-loaded PLGA NPs treatment dramatically reduced both T1ρ and T2 relaxation times at 4, 8, 12 weeks during administration, implying that cartilage destruction was alleviated. Histological assessments showed that RSV-loaded PLGA NPs significantly improved osteoarthritis symptoms. Gene expression analysis revealed that osteoarthritis mediator genes were downregulated in rats treated with RSV-PLGA NPs. Mechanistic studies indicated that RSV-loaded PLGA NPs inhibit apoptosis and promote autophagy. Collectively, this study demonstrates that intra-articular delivery of RSV via PLGA NPs might be an effective therapeutic approach for osteoarthritis.

Luteolin rescues postmenopausal osteoporosis elicited by OVX through alleviating osteoblast pyroptosis via activating PI3K-AKT signaling.

BACKGROUND: Recently, osteoblast pyroptosis has been proposed as a potential pathogenic mechanism underlying osteoporosis, although this remains to be confirmed. Luteolin (Lut), a flavonoid phytochemical, plays a critical role in the anti-osteoporosis effects of many traditional Chinese medicine prescriptions. However, its protective impact on osteoblasts in postmenopausal osteoporosis (PMOP) has not been elucidated. PURPOSE: This research aimed to determine the effect of Lut in ameliorating PMOP by alleviating osteoblast pyroptosis and sustaining osteogenesis. STUDY DESIGN: This research was designed to investigate the novel mechanism of Lut in alleviating PMOP both in cell and animal models. METHODS: Ovariectomy-induced PMOP models were established in mice with/without daily gavaged of 10 or 20 mg/kg body weight Lut. The impact of Lut on bone microstructure, metabolism and oxidative stress was evaluated with 0.104 mg/kg body weight Estradiol Valerate Tablets daily gavaged as positive control. Network pharmacological analysis and molecular docking were employed to investigate the mechanisms of Lut in PMOP treatment. Subsequently, the impacts of Lut on the PI3K/AKT axis, oxidative stress, mitochondria, and osteoblast pyroptosis were assessed. In vitro, cultured MC3T3-E1(14) cells were exposed to H2O2 with/without Lut to examine its effects on the PI3K/AKT signaling pathway, osteogenic differentiation, mitochondrial function, and osteoblast pyroptosis. RESULTS: Our findings demonstrated that 20 mg/kg Lut, similar to the positive control drug, effectively reduced systemic bone loss and oxidative stress, and enhanced bone metabolism induced by ovariectomy. Network pharmacological analysis and molecular docking indicated that the PI3K/AKT axis was a potential target, with oxidative stress response and nuclear membrane function being key mechanisms. Consequently, the effects of Lut on the PI3K/AKT axis and pyroptosis were investigated. In vivo data revealed that the PI3K/AKT axis was deactivated following ovariectomy, and Lut restored the phosphorylation of key proteins, thereby reactivating the axis. Additionally, Lut alleviated osteoblast pyroptosis and mitochondrial abnormalities induced by ovariectomy. In vitro, Lut intervention mitigated the inhibition of the PI3K/AKT axis and osteogenesis, as well as H2O2-induced pyroptosis. Furthermore, Lut attenuated ROS accumulation and mitochondrial dysfunction. The effects of Lut, including osteogenesis restoration, anti-pyroptosis, and mitochondrial maintenance, were all reversed with LY294002 (a PI3K/AKT pathway inhibitor). CONCLUSION: In summary, Lut could improve mitochondrial dysfunction, alleviate GSDME-mediated pyroptosis and maintain osteogenesis via activating the PI3K/AKT axis, offering a new therapeutic strategy for PMOP.

An ensemble learning model for predicting cancer-specific survival of muscle-invasive bladder cancer patients undergoing bladder preservation therapy.

Background: More muscle-invasive bladder cancer (MIBC) patients are now eligible for bladder-preserving therapy (BPT), underscoring the need for precision medicine. This study aimed to identify prognostic predictors and construct a predictive model among MIBC patients who undergo BPT. Methods: Data relating to MIBC patients were obtained from the Surveillance, Epidemiology and End Results (SEER) database from 2004 to 2016. Eleven features were included to establish multiple models. The predictive effectiveness was assessed using receiver operating characteristic (ROC) curves, calibration plots, decision curve analysis (DCA) and clinical impact curve (CIC). SHapley Additive exPlanations (SHAP) were used to explain the impact of features on the predicted targets. Results: The ROC showed that Catboost and Random Forest (RF) obtained better predictive discrimination in both 3- and 5-year models [test set area under curves (AUC) =0.80 and 0.83, respectively]. Furthermore, Catboost showed better performance in calibration plots, DCA and CIC. SHAP analysis indicated that age, M stage, tumor size, chemotherapy, T stage and gender were the most important features in the model for predicting the 3-year cancer-specific survival (CSS). In contrast, M stage, age, tumor size and gender as well as the N and T stages were the most important features for predicting the 5-year CSS. Conclusions: The Catboost model exhibits the highest predictive performance and clinical utility, potentially aiding clinicians in making optimal individualized decisions for MIBC patients with BPT.

[Inhibitory effect of nitric oxide-induced total ginsenosides on right ventricular hypertrophy in rats].

OBJECTIVE: To observe the effect of total ginsenosides (TG) on right ventricular hypertrophy induced by monocrotaline (MCT) in rats, and study its relationship with the nitric oxide pathway. METHOD: Male Sprague Dawley rats were randomly divided into the control group, the MCT model group, TG-treated (20, 40, 60 mg kg-1 d-1) groups, and the L-arginine (L-arg) th NO release, T + L-N and L-a + L-N groups were wi th NOS into study TG's effect 200 mg kg-1 d-1 group. Besides, and its relationship wi also set, intraperitoneally injected with TG 40 mg kg-1 d -1 and L-arg 200 mg kg-1 - d-1, and orally administered hibitor L-NAME 20 mg kg-1 d-1. After all of the groups were given drugs for 18 d, their right ventricular peak systolic pressure (RVSP) ventricular hypertrophy index (RVHI) and RVW/BW were determined. Ultra-structure of myocardial cells was observed with transmission electron microscope. The NO2 -/NO3 - content in myocardial tissues were detected with the nitrate reduction method. ANF and eNOS mRNA expressions in right ventricle tissues were detected by using real-time RT-PCR. RESULT: Low, middle and high doses of TG and L-arg preventive administration could significantly reduce RVSP, RVHI, RVW/BW and ANF mRNA expressions (P < 0. 05) , and ameliorate cellular mitochondrial swelling and degeneration. L-NAME could prevent the effect of L-arg on above indexes, whereas L-NAME of the same dose could not impact the reducing effect of TG 40 mg kg -1 on above indexes. TG 60 mg kg -1 could raise eNOS mRNA expression, but TG 20 mg kg-1 and 40 mg kg-1 showed no effect. CONCLUSION: TG can significantly attenuate MCT-induced right cardiac hypertrophy in rats. Its anti-hypertrophic effect is partially realized through NO.

Resveratrol protects osteocytes against oxidative stress in ovariectomized rats through AMPK/JNK1-dependent pathway leading to promotion of autophagy and inhibition of apoptosis.

A large number of studies in recent years indicate that osteocytes are the orchestrators of bone remodeling by regulating both osteoblast and osteoclast activities. Oxidative stress-induced osteocyte apoptosis plays critical roles in the pathological processes of postmenopausal osteoporosis. Resveratrol is a natural polyphenolic compound that ameliorates postmenopausal osteoporosis. However, whether resveratrol regulates osteocyte apoptosis via autophagy remains largely unknown. The effects of resveratrol on regulating osteocyte apoptosis and autophagy were analyzed both in vivo and in vitro. In vitro, cultured MLO-Y4 cells were exposed to H2O2 with or without resveratrol. In vivo, an ovariectomy-induced osteoporosis model was constructed in rats with or without daily intraperitoneal injection of 10 mg/kg body weight resveratrol. It was found that resveratrol attenuated H2O2-induced apoptosis through activating autophagy in cultured MLO-Y4 cells, which was mediated by the dissociation of Beclin-1/Bcl-2 complex in AMPK/JNK1-dependent pathway, ultimately regulating osteocytes function. Furthermore, it was shown that resveratrol treatment reduced osteocytes oxidative stress, inhibited osteocytes apoptosis and promoted autophagy in ovariectomized rats. Our study suggests that resveratrol protects against oxidative stress by restoring osteocytes autophagy and alleviating apoptosis via AMPK/JNK1 activation, therefore dissociating Bcl-2 from Beclin-1.

Electrical Tree Characteristics of Bisphenol A Epoxy Resin/Maleopimaric Anhydride Curing System.

Epoxy resin insulation materials are mainly derived from petrochemical materials which have the disadvantages of resource consumption and environmental pollution. In order to cure bisphenol A epoxy resin, a maleopimaric anhydride (MPA) curing agent was prepared from rosin, a renewable resource, and blended with a petroleum-based curing agent (methylhexahy-drophthalic anhydride). The influence of maleopimaric anhydride content on the initiation and growth characteristics of electrical trees was studied and analyzed in this paper using molecular dynamics simulation (MD) and electrical tree tests at an 18-kilovolt power frequency voltage. When the MPA content used was ≤10%, the free volume percentage of the curing system increased with MPA content, and thus the initiation voltage became lower; when the MPA content was ≥20%, the hydrogenated phenanthrene ring structure content increased significantly with increasing MPA content, and the rigidity of the curing system increased significantly; thus, the initiation voltage gradually increased. MPA4 had an 11.11% higher initiation voltage than the petroleum-based control group. The effect of the polar rigid structure within the curing system significantly inhibited the growth rate and length of electrical trees as MPA content increased. Electrical trees developed into light-colored, thin, and narrow dendritic structures when the MPA content reached 40%. The results show that curing epoxy resin with the rosin-based curing agent maleopimaric anhydride (MPA), in place of a petroleum-based curing agent, can produce environmentally friendly resins with excellent electrical tree resistance and potential application prospects.

Performance Research and Formulation Optimization of High-Performance Local Insulation Spray Coating Materials.

Bird pest control has become a major task for the operation and maintenance of distribution network lines. Epoxy resin that cures quickly at room temperature can be used to coat locations where birds frequently build their nests. However, epoxy resin has enormous internal stress and is brittle, so it is essential to toughen it. In this paper, for a room temperature curing system composed of polyurethane-modified epoxy resin and a polythiol curing agent, three kinds of particles, i.e., Al2O3, SiO2, and Mg(OH)2, were used to modify a polyurethane modified epoxy resin. Orthogonal experiments were designed to study the effects of different fillers on the comprehensive properties of polyurethane-modified epoxy resins. The experimental results showed that there were not only independent effects of different kinds if particles on the resin, but also synergistic effects of multiple particles. Nanoparticles can reduce the defects introduced by microparticles to a certain extent and improve the mechanical and electrical properties of the resin. The overall performance of the resin was optimized when the amounts of SiO2, Al2O3, and Mg(OH)2 were 1.7%, 2.5%, and 7%, respectively. The tensile strength of the resin was increased by 70%, the elongation at a break by 67.53%, and the breakdown strength by 20.31% compared with before the addition of filler. The microscopic morphology and thermal properties of the resin before and after the addition of filler were also studied. Adding fillers caused more cracks to absorb part of the energy when the resin matrix was stressed and increased the rigidity of the resin matrix and the resin's glass transition temperature (Tg) by 13.48 °C. Still, the temperature corresponding to the maximum rate of weight loss (Tmax) remained unchanged.

Development and validation of a prognostic nomogram for predicting cancer-specific survival in patients with metastatic clear cell renal carcinoma: A study based on SEER database.

Objectives: Clear cell renal cell carcinoma (ccRCC) is highly prevalent, prone to metastasis, and has a poor prognosis after metastasis. Therefore, this study aimed to develop a prognostic model to predict the individualized prognosis of patients with metastatic clear cell renal cell carcinoma (mccRCC). Patients and Methods: Data of 1790 patients with mccRCC, registered from 2010 to 2015, were extracted from the Surveillance, Epidemiology and End Results (SEER) database. The included patients were randomly divided into a training set (n = 1253) and a validation set (n = 537) based on the ratio of 7:3. The univariate and multivariate Cox regression analyses were used to identify the important independent prognostic factors. A nomogram was then constructed to predict cancer specific survival (CSS). The performance of the nomogram was internally validated by using the concordance index (C-index), calibration plots, receiver operating characteristic curves, net reclassification improvement (NRI), integrated discrimination improvement (IDI), and decision curve analysis (DCA). We compared the nomogram with the TNM staging system. Kaplan-Meier survival analysis was applied to validate the application of the risk stratification system. Results: Diagnostic age, T-stage, N-stage, bone metastases, brain metastases, liver metastases, lung metastases, chemotherapy, radiotherapy, surgery, and histological grade were identified as independent predictors of CSS. The C-index of training and validation sets are 0.707 and 0.650 respectively. In the training set, the AUC of CSS predicted by nomogram in patients with mccRCC at 1-, 3- and 5-years were 0.770, 0.758, and 0.757, respectively. And that in the validation set were 0.717, 0.700, and 0.700 respectively. Calibration plots also showed great prediction accuracy. Compared with the TNM staging system, NRI and IDI results showed that the predictive ability of the nomogram was greatly improved, and DCA showed that patients obtained clinical benefits. The risk stratification system can significantly distinguish the patients with different survival risks. Conclusion: In this study, we developed and validated a nomogram to predict the CSS rate in patients with mccRCC. It showed consistent reliability and clinical applicability. Nomogram may assist clinicians in evaluating the risk factors of patients and formulating an optimal individualized treatment strategy.

Artificial Intelligence Combined With Big Data to Predict Lymph Node Involvement in Prostate Cancer: A Population-Based Study.

BACKGROUND: A more accurate preoperative prediction of lymph node involvement (LNI) in prostate cancer (PCa) would improve clinical treatment and follow-up strategies of this disease. We developed a predictive model based on machine learning (ML) combined with big data to achieve this. METHODS: Clinicopathological characteristics of 2,884 PCa patients who underwent extended pelvic lymph node dissection (ePLND) were collected from the U.S. National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2015. Eight variables were included to establish an ML model. Model performance was evaluated by the receiver operating characteristic (ROC) curves and calibration plots for predictive accuracy. Decision curve analysis (DCA) and cutoff values were obtained to estimate its clinical utility. RESULTS: Three hundred and forty-four (11.9%) patients were identified with LNI. The five most important factors were the Gleason score, T stage of disease, percentage of positive cores, tumor size, and prostate-specific antigen levels with 158, 137, 128, 113, and 88 points, respectively. The XGBoost (XGB) model showed the best predictive performance and had the highest net benefit when compared with the other algorithms, achieving an area under the curve of 0.883. With a 5%~20% cutoff value, the XGB model performed best in reducing omissions and avoiding overtreatment of patients when dealing with LNI. This model also had a lower false-negative rate and a higher percentage of ePLND was avoided. In addition, DCA showed it has the highest net benefit across the whole range of threshold probabilities. CONCLUSIONS: We established an ML model based on big data for predicting LNI in PCa, and it could lead to a reduction of approximately 50% of ePLND cases. In addition, only ≤3% of patients were misdiagnosed with a cutoff value ranging from 5% to 20%. This promising study warrants further validation by using a larger prospective dataset.

A Novel Machine Learning Algorithm Combined With Multivariate Analysis for the Prognosis of Renal Collecting Duct Carcinoma.

OBJECTIVES: To investigate the clinical and non-clinical characteristics that may affect the prognosis of patients with renal collecting duct carcinoma (CDC) and to develop an accurate prognostic model for this disease. METHODS: The characteristics of 215 CDC patients were obtained from the U.S. National Cancer Institute's surveillance, epidemiology and end results database from 2004 to 2016. Univariate Cox proportional hazard model and Kaplan-Meier analysis were used to compare the impact of different factors on overall survival (OS). 10 variables were included to establish a machine learning (ML) model. Model performance was evaluated by the receiver operating characteristic curves (ROC) and calibration plots for predictive accuracy and decision curve analysis (DCA) were obtained to estimate its clinical benefits. RESULTS: The median follow-up and survival time was 16 months during which 164 (76.3%) patients died. 4.2, 32.1, 50.7 and 13.0% of patients were histological grade I, II, III, and IV, respectively. At diagnosis up to 61.9% of patients presented with a pT3 stage or higher tumor, and 36.7% of CDC patients had metastatic disease. 10 most clinical and non-clinical factors including M stage, tumor size, T stage, histological grade, N stage, radiotherapy, chemotherapy, age at diagnosis, surgery and the geographical region where the care delivered was either purchased or referred and these were allocated 95, 82, 78, 72, 49, 38, 36, 35, 28 and 21 points, respectively. The points were calculated by the XGBoost according to their importance. The XGBoost models showed the best predictive performance compared with other algorithms. DCA showed our models could be used to support clinical decisions in 1-3-year OS models. CONCLUSIONS: Our ML models had the highest predictive accuracy and net benefits, which may potentially help clinicians to make clinical decisions and follow-up strategies for patients with CDC. Larger studies are needed to better understand this aggressive tumor.

Effect of particle size on the stability and flavor of cloudy apple juice.

Different particle sizes in cloudy apple juice were obtained following filtration with different mesh sizes (100, 200, 300, and 400-mesh). The effects of cloud particle size on the stability, nutrient content, and volatile flavor of cloudy apple juice were evaluated. With increasing mesh number, particle size decreased (p < 0.05) and particle shape changed. Particle size had an effect on volatile flavor compounds, especially nitrogen oxides, alcohols, and aromatic compounds. The content of pectin and total phenol decreased with decreasing particle size, while the content of soluble protein was not affected. The reduction of cloud particle size increased absolute value of ζ-potential, cloud stability, and apparent viscosity and decreased turbidity and cloud values. Pearson correlation analysis showed that there was a strong correlation between particle size and quality indicators, except for soluble protein.