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Abstract Pancreatic ductal adenocarcinoma (PDAC) is considered the third leading cause of cancer mortality in the western world, offering advanced stage patients with few viable treatment options. Consequently, there remains an urgent unmet need to develop novel therapeutic strategies that can effectively inhibit pro-oncogenic molecular targets underpinning PDACs pathogenesis and progression. One such target is c-RAF, a downstream effector of RAS that is considered essential for the oncogenic growth and survival of mutant RAS-driven cancers (including KRASMT PDAC). Herein, we demonstrate how a novel cell-penetrating peptide disruptor (DRx-170) of the c-RAF–PDE8A protein–protein interaction (PPI) represents a differentiated approach to exploiting the c-RAF–cAMP/PKA signaling axes and treating KRAS–c-RAF dependent PDAC. Through disrupting the c-RAF–PDE8A protein complex, DRx-170 promotes the inactivation of c-RAF through an allosteric mechanism, dependent upon inactivating PKA phosphorylation. DRx-170 inhibits cell proliferation, adhesion and migration of a KRASMT PDAC cell line (PANC1), independent of ERK1/2 activity. Moreover, combining DRx-170 with afatinib significantly enhances PANC1 growth inhibition in both 2D and 3D cellular models. DRx-170 sensitivity appears to correlate with c-RAF dependency. This proof-of-concept study supports the development of DRx-170 as a novel and differentiated strategy for targeting c-RAF activity in KRAS–c-RAF dependent PDAC.

Objective Knee kinematic asymmetries after anterior cruciate ligament reconstruction (ACLR) are correlated with poor clinical outcomes, such as the progression of knee cartilage degenerations or reinjuries. Fast walking in patients with knee conditions may exacerbate knee kinematic asymmetries, but its impact on ACLR patients is uncertain. The aim of this study is to investigate if fast walking induces more knee kinematic asymmetries in unilateral ACLR patients. Methods This cross‐sectional study enrolled 55 patients with unilateral ACLR from January 2020 to July 2022. There were 48 males and seven females with an average age of 30.6 ± 6.4 years. Knee kinematic data were collected at three walking speeds: self‐selected, fast (150% normal), and slow (50% normal). A 3D knee kinematic analysis system measured the data, and self‐reported outcomes assessed comfort levels during walking. We used SPM1D for two‐way repeated ANOVA and posthoc paired t‐tests to analyze kinematic differences in groups. Results In fast walking, ACLR knees exhibited more transverse kinematic asymmetries than intact knees, including greater external rotation angle (1.8°, 38%–43%; gait cycle [GC], p

Summary: Background: Genetic variants in COL4A1 and COL4A2 (encoding collagen IV alpha chain 1/2) occur in genetic and sporadic forms of cerebral small vessel disease (CSVD), a leading cause of stroke, dementia and intracerebral haemorrhage (ICH). However, the molecular mechanisms of CSVD with ICH and COL4A1/COL4A2 variants remain obscure. Methods: Vascular function and molecular investigations in mice with a Col4a1 missense mutation and heterozygous Col4a2 knock-out mice were combined with analysis of human brain endothelial cells harboring COL4A1/COL4A2 mutations, and brain tissue of patients with sporadic CSVD with ICH. Findings: Col4a1 missense mutations cause early-onset CSVD independent of hypertension, with enhanced vasodilation of small arteries due to endothelial dysfunction, vascular wall thickening and reduced stiffness. Mechanistically, the early-onset dysregulated endothelium-dependent hyperpolarization (EDH) is due to reduced collagen IV levels with elevated activity and levels of endothelial Ca2+-sensitive K+ channels. This results in vasodilation via the Na/K pump in vascular smooth muscle cells. Our data support this endothelial dysfunction preceding development of CSVD-associated ICH is due to increased cytoplasmic Ca2+ levels in endothelial cells. Moreover, cerebral blood vessels of patients with sporadic CSVD show genotype-dependent mechanisms with wall thickening and lower collagen IV levels in those harboring common non-coding COL4A1/COL4A2 risk alleles. Interpretation: COL4A1/COL4A2 variants act in genetic and sporadic CSVD with ICH via dysregulated EDH, and altered vascular wall thickness and biomechanics due to lower collagen IV levels and/or mutant collagen IV secretion. These data highlight EDH and collagen IV levels as potential treatment targets. Funding: MRC, Wellcome Trust, BHF.

Abstract Background The objective of this research was to elucidate the association between the length of infertility and the outcomes of intrauterine insemination (IUI) in women of varying ages - a topic that has been the subject of investigation for numerous years, yet lacks a definitive consensus. Methods A retrospective cohort investigation involving 5268 IUI cycles was undertaken at the Reproductive Medicine Center of Nanjing Drum Tower Hospital from 2016 to 2022. Utilizing the smooth fitting curve along with threshold and saturation effect analysis, the correlation between infertility duration and IUI clinical pregnancy rates was discerned. Moreover, patients were bifurcated into two cohorts based on their respective infertility durations. A secondary examination was also performed employing propensity-score matching to mitigate the impact of confounding variables. Subsequent threshold and saturation effect analysis was carried out across various subgroups, segmented on the basis of age differentiation. Results When the duration of infertility was more than 5 years, the clinical pregnancy rate decreased with the increase of infertility duration (aOR: 0.894, 95%CI: 0.817–0.991, p = 0.043). The multivariate regression analysis suggested that longer duration of infertility (≥ 5 years) was significantly correlated with the lower clinical pregnancy rate (aOR: 0.782, 95% CI: 0.643–0.950, p = 0.01). After the propensity-score matching, the clinical pregnancy rate of women with longer infertility duration were also higher. When the duration of infertility was more than 5 years, the clinical pregnancy rate of women younger than 35 years old decreased with the increase of infertility duration (aOR: 0.906, 95%CI: 0.800–0.998, p = 0.043). Conclusions The clinical pregnancy rate and live birth rate of IUI in young women (

Objective·To investigate the efficacy and safety of hypertonic dextrose prolotherapy (DPT) in the treatment of postherpetic neuralgia.Methods·Seventy-eight patients with postherpetic neuralgia who visited the Department of Pain of The Affiliated Hospital of Xuzhou Medical University from June 2019 to December 2022 were selected. The patients were randomly assigned to a control group and a research group in a 1∶1 ratio, with 39 patients in each group. The control group was treated with traditional analgesic solution, while the research group was treated with traditional analgesic solution combined with DPT. Visual analog scale (VAS) was used to evaluate the patients' pain level before and after treatment, flow cytometry was used to measure the patients' T-cell subsets, and enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of C-reactive protein (CRP), interleukin-6 (IL-6), and IL-10 cytokines. The VAS scores were compared between the two groups of patients before and at 1, 2, 4, 8, and 12 weeks after treatment. CD4+/CD8+, CRP, IL-6, IL-10 levels, and the incidence of adverse reactions before and 2 weeks after treatment were compared between the two groups.Results·There was no statistically significant difference in sex ratio, age, and disease duration between the two groups of patients. The VAS scores of the two groups of patients at 1, 2, 4, 8, and 12 weeks after treatment were significantly lower than those before treatment, and the differences were statistically significant (all P

Abstract Yin Yang 1 (YY1) is a key transcription factor that has been implicated in the development of several malignancies. The stability of YY1 is regulated by the ubiquitin-proteasome system. The role of deubiquitinases (DUBs) and their impact on YY1 remain to be fully elucidated. In this study, we screened for ubiquitin-specific proteases that interact with YY1, and identified OTUD3 as a DUB for YY1. Over-expressed OTUD3 inhibited YY1 degradation, thereby increasing YY1 protein levels, whereas OTUD3 knockdown or knockout promoted YY1 degradation, thereby decreasing the proliferation of colorectal cancer (CRC). Furthermore, PLK1 mediates OTUD3 S326 phosphorylation, which further enhances OTUD3 binding and deubiquitination of YY1. In CRC tissues, elevated the expression level of OTUD3 and YY1 were significantly associated with poor prognostic outcomes. These findings suggest that the OTUD3-YY1 pathway has therapeutic potential in CRC, and OTUD3 plays a critical role in regulating YY1.

The content of ethanol in wine can affect its quality. Some edible alcohol contains small amounts of methanol, and its accumulation can cause serious health problems. Therefore, it is very important to test the contents of methanol and ethanol in alcohol products. In this paper, a rapid method for the determination of methanol and ethanol by ambient corona discharge ionization mass spectrometry was developed. The method is based on the interaction of water radical cation with methanol and ethanol, respectively. In the positive ion mode, the water dimer radical cation (H2O)2+· (m/z 36) with ambient corona discharge ionization source was prepared by using ambient corona discharge ionization source, and it was introduced into the mass spectrometer with methanol or ethanol through a dual-channel low-energy corona discharge ionization device. The two reacted with each other to form the corresponding water radical cationic complex [CH3OH+H2O]+· (m/z 50) and [CH3CH2OH+H2O]+· (m/z 64), which realized the direct and rapid qualitative and quantitative analysis of methyl alcohol and ethanol in different kinds of alcoholic beverages. The result showed that the limits of detection and the limits of quantification of methanol and ethanol were 0.011 and 0.004 mg/L, 0.038 and 0.014 mg/L, respectively. The correlation coefficients of the target ionic strength curves obtained by the interaction of different concentrations of standard methanol and ethanol with water free radical cation could reach to 0.990 4 and 0.991 1, respectively. By using this method, no methanol was detected in common alcoholic drinks, and the ethanol content in liquor was higher than beer. In the actual work, the method has good practicability through the experimental exploration and verification of different wines. This method does not require sample pretreatment, has the advantages of simple operation and fast analysis, and is especially suitable for the detection of aqueous system. This study has important guiding significance for the quantitative detection and analysis of methanol and ethanol in complex system, provides technical support for the detection of alcoholic beverages and food, and also provides an effective strategy for the quantitative detection of the content of small and medium molecular alcohols in actual samples.

Purpose The objective was to describe the technique and clinical outcome of microwave thermal ablation (MWA) and perfusion combined with synthetic bone substitutes in treating unicameral bone cysts (UBCs) in adolescents.Materials and Methods A total of 14 consecutive patients were enrolled by percutaneous MWA and saline irrigation combined with synthetic bone substitutes. Clinical follow-up included the assessment of pain, swelling, and functional mobility. Radiological parameters included tumor volume, physis-cyst distance, cortical thickness of the thinnest cortical bone, and the Modified Neer classification system.Results The mean follow-up was 28.9 months (26–52 months). All UBCs were primary, and all patients underwent the MWA, saline perfusion, and reconstruction combined with a synthetic bone substitute session, except for one patient (7.1%) who required a second session. All patients had good clinical results at the final follow-up. Satisfactory cyst healing was achieved in 13 cases according to radiological parameters. Tumor volume decreased from a mean of 49.7 cm3 before surgery treatment to 13.9 cm3 at the final follow-up (p

Abstract Layered thio- and seleno-phosphate ferroelectrics, such as CuInP2S6, are promising building blocks for next-generation nonvolatile memory devices. However, because of the low Curie point, the CuInP2S6-based memory devices suffer from poor thermal stability (

As the “smart sports” continue to heat up, some colleges and universities have launched the first practice in sports in terms of information technology and extensive data management. In this paper, we first constructed an innovative sports public service platform using information technology, created an intelligent management mode of sports in colleges and universities, and realized the synergistic governance of services and management of sports. Then, based on entropy weight-TOPSIS method, it constructed an evaluation model for the quality of intelligent sports management. It solved the implementation effect of college innovative sports from informationization management matching degree, safety management feedback and informationization sports teaching feedback. The results show that the average value of the feedback scores for college sports safety management is above 35 points. Students’ learning engagement and sports interest before and after the introduction of sports teaching management in colleges and universities showed significant differences at the 1% level. The research presented in this paper is conducive to deepening and expanding theoretical research on topics such as computerized sports management and campus sports, and promoting modernization and development of sports teaching and management.

This network meta‐analysis aims to evaluate the comparative effectiveness and safety of suture anchors (SA), tendon grafts (TG), hook plates (HP), Tight‐Rope (TR), and EndoButton (EB) in the treatment of acute acromioclavicular joint (ACJ) dislocation. The Embase, PubMed, and Web of Science databases were searched from their inception date to June 3, 2022. Studies included all eligible randomized controlled trials (RCTs) and cohort studies with the comparison of five different fixation systems among SA, TG, HP, TR, and EB were identified. All studies were reviewed, performed data extraction, and assessed the risk of bias independently by two reviewers. The primary outcomes are Constant–Murley score (CMS) improvement for assessing clinical efficacy, and complications. The second outcomes are visual analog scale (VAS) for assessing pain relief and the coracoclavicular distance (CCD) for assessing postoperative joint reduction. Version 2 of the revised Cochrane risk of bias tool for randomized trials (RoB 2) and the risk of bias in nonrandomized studies of interventions (ROBINS‐I) were used to assess the RCTs and non‐randomized trials, respectively. The continuous outcomes were presented as mean differences (MD), and risk ratios (OR) were used for dichotomous outcomes, both with 95% confidence intervals (CI). Surface under the cumulative ranking curves (SUCRA) results were calculated to offer a ranking of each intervention. We identified 31 eligible trials, including 1687 patients in total. HP showed less CMS improvement than TR and EB in both the Network Meta‐analysis (NMA) and pairwise meta‐analysis. HP also showed less CMS improvement than SA in NMA. For pain relief, HP performed worse than TR both in pairwise meta‐analysis and NMA. No significant differences were found for the measured value of CCD. Both TR and EB showed a lower incidence of complications than HP in pairwise meta‐analysis. The rank of SUCRA for CMS improvement was as follows: SA, TR, EB, TG, and HP; for pain relief: TR, EB, TG, SA, and HP; for CCD: HP, TR, SA, EB, and TG. For complications, HP showed the highest rank, followed by TG, EB, TR, and SA. SA shows better clinical effectiveness and reliable safety in the treatment of acute ACJ dislocation. Although HP is the most widely used surgical option currently, it should be carefully taken into consideration for its high incidence of complications.

Abstract Partial discharge (PD) diagnosis is a crucial tool to assess the insulation condition of wind farm cables. Among PD diagnosis techniques, PD localisation is promising as it can provide target maintenance indicators on the insulation weak points of the cables. Accordingly, this paper developed a portable PD detection and location system for wind farm inter‐array cables. The system consists of two non‐invasive and lightweight testing units, which can be conveniently deployed on an energised cable, enabling highly efficient online PD diagnosis of the widely distributed inter‐array cables. The system achieves accurate PD localisation of the energised cable via an improved double‐sided travelling wave method. The method exhibits two superior features: the double‐sided testing units are accurately synchronised via the joint application of Global Position Systems and a pulse‐based interaction process, and a windowed phase difference method is proposed and integrated into the system to robustly estimate the time‐of‐arrival difference in low signal‐to‐noise ratio environment. Validation experiments were conducted on both a 10‐kV cable in the laboratory and a real 35‐kV cable in an on‐shore wind farm.

Summary: Mixed-dimensional heterostructures have drawn significant attention due to their intriguing physical properties and potential applications in electronic and optoelectronic nanodevices. However, limited by the lattice matching, the preparation of heterostructures is experimentally difficult and the underlying growth mechanism has not been well established. Here, we report a three-step seeding epitaxial growth strategy for synthesizing mixed-dimensional heterostructures of one-dimensional microwire (MW) and two-dimensional atomic thin film. Our growth strategy has successfully realized direct epitaxial growth of WSe2 film on WOx MW and significantly improves the quality of the epitaxial WSe2 monolayer, which is evidenced by the remarkably enhanced photoluminescence (PL). More intriguingly, the as-synthesized WOx MWs exhibit a strong nonlinear optical response due to the enhancement effect of the core (WOx)-shell (WSe2) nanocavity. Our work provides a feasible route for direct growth of WOx-based mixed-dimensional heterostructures, which possess potential applications in high-performance optoelectronic devices.

Condition-based maintenance of cables in wind farms is critical for their operation reliability and stability. A promising solution to this task is to carry out on-line partial discharge measurement on the cables. However, impulse noise interferences from wind turbines or adjacent overhead lines could severely reduce the sensitivity of in field partial discharge measurement. Accordingly, this paper proposes a robust method to recognize the harmful partial discharge signal from the severe impulse noise. The method is based on joint analysis of the noisy partial discharge signals detected by two non-invasive partial discharge sensors, which are mounted on the double sides of the cable or on its terminal. The noiseless partial discharge signal and the impulse noise can be separated well via performing statistical clustering analysis on the pulse source location map or peak ratio vector obtained from the two detected noisy signal sequences. Finally, the effectiveness and feasibility of the proposed method is validated on two real partial discharge-affected 35-kV cables in an onshore wind farm.

Abstract Background Although repeated cryopreservation is an occasional occurrence, the effect on perinatal outcomes is unclear. Therefore, the aim of this study was to evaluate the perinatal outcomes of singletons after embryo re-cryopreservation. Methods In this retrospective study, a total of 647 singleton live births after blastocyst freeze-thaw embryo transfer cycles were investigated. They were divided into two groups: vitrified-warmed blastocysts (once-vitrified group) and vitrified-warmed blastocysts derived from thawed cleaved embryos (re-vitrified group). Propensity score matching (PSM) was used to control for potential confounding factors. Results A total of 592 infants were included in the once-vitrified group, and 55 infants were included in the re-vitrified group. After PSM, 108 cases were generated for comparison. The median gestational age was 38 weeks for both groups, and the birthweights were comparable (3390.6 ± 601.5 g vs. 3412.8 ± 672.6 g, P > 0.05). The incidence of preterm birth (PTB) (20.4% vs. 16.7%), low birthweight (LBW) (3.7% vs. 7.4%), macrosomia (11.1% vs. 16.7%) and large for gestational age (LGA) (29.6% vs. 22.2%) were not significantly different between the two groups. Logistic regression analysis indicated that double vitrification-warming procedures did not affect the occurrence of PTB (OR, 2.58 [95% CI, 0.77, 8.63]), LBW (OR, 0.83 [95% CI, 0.08, 8.29]), macrosomia (OR, 0.60 [95% CI, 0.13, 2.69]), or LGA (OR, 1.51 [95% CI, 0.53, 4.27]) (P > 0.05, for all). Conclusion Our findings demonstrate that double vitrification-warming procedures do not increase the risk of adverse neonatal outcomes compared with those of once-vitrified embryos.

Abstract Background Infertility is one of the most important and underappreciated reproductive health problems in developing countries. Currently, in vitro fertilization and embryo transfer is the most effective treatment strategy for infertility. In a frozen-thawed cycle, single-blastocyst transfer can not only ensure relatively higher pregnancy and live birth rates but also effectively reduce the risk of maternal and neonatal complications. In frozen-thawed cycles, progesterone is initiated to promote the final phase of endometrial preparation prior to embryo transfer. However, the optimal duration of exposure to progesterone has remained inconclusive. Therefore, we designed a randomized controlled trial (RCT) to compare the effects of different prolonged progesterone transformation times (P+6 and P+7) on the pregnancy outcomes of D6 single blastocyst transfer in a frozen-thawed cycle. Methods This is a single-center, prospective, randomized controlled clinical trial involving 900 patients with single blastocyst transfer in the frozen-thawed cycle, aged from 20 to 38 years, with less than three transfers, and with HRT-cycle single D6 blastocyst transfer in the current cycle. Participants will be randomly assigned (1:1) into two parallel groups: the transfer of day 6 blastocysts on the 7th day of progesterone supplementation and the transfer of day 6 blastocysts on the 6th day of progesterone supplementation. The primary outcome measure is the clinical pregnancy rate. Secondary outcome measures include the miscarriage rate and live birth rate. Discussion This is the first randomized controlled trial to compare the transfer of day 6 blastocysts on the 6th and 7th day of progesterone supplementation. The results of this study will provide evidence for whether to prolong the duration of exposure to progesterone prior to embryo transfer. Trial registration ClinicalTrials.gov, ID: NCT04938011. Registered on 19 June 2021.

Diabetic kidney dysfunction is closely associated with renal fibrosis. Although the suppression of fibrosis is crucial to attenuate kidney damage, the underlying mechanisms remain poorly understood. In this study, renal injury in diabetic mice was induced by the intraperitoneal injection of streptozotocin (100 or 150 mg/kg) for 2 consecutive days. In the model mice, remarkable renal injury was observed, manifested by albuminuria, swelling of kidneys, and histopathological characteristics. The renal fibrosis was obviously displayed with high-intensity staining of fibrin, type IV collagen (Col IV), and fibronectin. The levels of Col IV and transforming growth factor-β1 were significantly increased in diabetic mice kidneys. The aggravated fibrotic process was associated with the overexpression of HMGB1, TLR2/4, and p-NF-κB. Furthermore, a high expression of F4/80 and CD14 indicated that macrophage infiltration was involved in perpetuating inflammation and subsequent fibrosis in the kidneys of diabetic mice. The results demonstrate that the severity of renal fibrosis is positively associated with the activation of HMGB1/TLR2/4 signaling in diabetes.

Research questionHormone replacement therapy (HRT) is one of the most used endometrial preparation protocols for frozen embryo transfer (FET) due to the convenience of its administration and stability of pregnancy outcomes. There are several HRT cycles accompanied by the development of dominant follicles. However, the relationship between dominant follicle development and clinical outcomes in HRT-FET cycles remains unclear.DesignWe carried out a retrospective cohort study of 13251 cycles at our reproductive medicine center from 2012 to 2019. Total cycles were divided into two groups according to whether there was dominant follicular development. In addition, we conducted a secondary analysis that used propensity-score matching to reduce confounding variables. A univariate and multivariable logistic regression model was further employed to analyze the effect of dominant follicle development in HRT cycles on clinical pregnancy outcomes.ResultsThere was no significant correlation between dominant follicle development in HRT-FET cycles and the clinical pregnancy rate (adjusted OR = 1.162, 95% CI: 0.737-1.832, P = 0.52). In addition, there was a positive correlation between the basic follicle-stimulating hormone (FSH) level and the development of dominant follicles, while there was a negative correlation between antral follicle count (AFC), menstrual cycle length and the development of dominant follicles in HRT cycles.ConclusionsThe development of dominant follicles in HRT-FET cycles does not affect the clinical pregnancy rate, early miscarriage rate and live birth rate. Therefore, it is not necessary to immediately cancel the FET cycle immediately when dominant follicle development is monitored in the HRT-FET cycle.

The mechanical properties of polyurethane grouting materials were significantly improved when cement, sodium meta-silicate, red mud, slag, and fly ash were added. However, the grouting mechanisms of polyurethane composite materials are not clear. The grouting mechanisms of polyurethane composite materials in asphalt pavement subsidence were investigated. The results of computed tomography analysis show that polyurethane foam is filled with geopolymer hydration products. The results from ground penetrating radar after grouting show that mapping has no significant fluctuation or dislocation effect, which indicates that the grouting effect is strong. The high-density electrometer can also test the pavement subsidence place and distribution. The grouting mechanisms indicate that polyurethane foam acts as the consolidation structure, and the geopolymer filled with the foam pores of polyurethane and geopolymer forms a stable consolidated body. The seriflux includes under-layer seriflux (red mud, slag, water, and polyurethane composite materials) and upper-layer seriflux (polyurethane seriflux), and there exists a weak phase separation phenomenon, in which the separation phase is mainly polyurethane with little red mud-based geopolymer.

Abstract Background Poor decidualization and abnormal autophagy conditions in the endometria of adenomyosis patients have been reported previously. However, the specific regulatory mechanism of decidualization in adenomyosis and its relationship with autophagy levels have not been clarified. Methods Endometrial tissues from adenomyosis patients and uteri from an adenomyosis mouse model were collected for the detection of different expression patterns of KLF4 and autophagy markers (LC3-B/LC3-A and Beclin-1) compared with control groups. Human endometrial stromal cells (hESCs) isolated from adenomyosis and control endometrial tissues were employed to elucidate the biological functions of KLF4 in autophagy and decidualization. Gene expression regulation was examined by quantitative real-time PCR (qRT-PCR), western blotting and luciferase reporter assays. In addition, DNA promoter-protein interactions were examined by chromatin immunoprecipitation (ChIP)/PCR assay and avidin–biotin conjugate DNA precipitation (ABCD) assay. Results KLF4 expression was decreased in endometrial tissues from adenomyosis patients compared with those from fertile controls, especially in stromal compartments. The opposite results were observed for autophagy marker (LC3-B/LC3-A and Beclin-1) expression. At the same time, KLF4 reversed the poor decidualization of hESCs from adenomyosis patients. In addition, KLF4 could induce hESC decidualization by promoting the autophagy level. Mechanistically, KLF4 bound to a conserved site in the autophagy-related 5 (ATG5) promoter region and promoted ATG5 expression. Similar expression patterns of KLF4 and autophagy markers were detected in adenomyotic mice. Conclusions KLF4 overexpression increases the autophagy level of hESCs by transcriptionally promoting ATG5 expression, and abnormally decreased KLF4 in adenomyosis impairs hESC decidualization by repressing autophagy.

Abstract Background In our previous study, activin B in combination with ADSCs enhances skin wound healing. However, the underlying molecular mechanisms are not well studied. Cdc42 is recognized to play a critical role in the regulation of stem cells. Methods Pull-down assay was performed to investigate the activity of Cdc42. The dominant-negative mutant of Cdc42 (Cdc42N17) was used to explore the role of Cdc42 in activin B-induced ADSCs migration, proliferation, and secretion in vitro. Cdc42N17-transfected ADSCs were injected into a full-thickness excisional wound model to explore their efficiency in wound healing in vivo. The wound healing efficacy was evaluated by the wound closure rates and histological examination. The neovascularization and wound contraction were detected by immunohistochemistry staining of CD31 and α-SMA. Finally, the underlying mechanisms were explored by RNA sequencing. Results Cdc42N17 inhibited ADSCs migration, proliferation, and secretion induced by activin B. Furthermore, Cdc42N17-transfected ADSCs inhibited the wound closure rate and suppressed the expression of CD31 and α-SMA induced by activin B in vivo. The RNA sequencing showed that the differentially expressed genes in Cdc42N17-transfected ADSCs versus ADSCs were associated with cell migration, proliferation, and adhesion. Further study revealed that the Cdc42-Erk-Srf pathway was required for activin B-induced proliferation in ADSCs. Conclusions Our study indicates that Cdc42 plays a crucial role in ADSCs-mediated skin wound healing induced by activin B. Graphical Abstract

Abstract Background The use of keratinocytes derived from induced pluripotent stem cells (iPSCs-KCs) may represent a novel cell therapy strategy for burn treatment. There is growing evidence that extracellular vesicles, including exosomes, are primary mediators of the benefits of stem cell therapy. Herein, we thus explored the effects of exosomes produced by iPSCs-derived keratinocytes (iPSCs-KCs-Exos) in a model of deep second-degree burn wound healing and evaluated the mechanistic basis for the observed activity. Methods iPSCs-KCs-Exos were isolated from conditioned medium of iPSCs-KCs and verified by electron micrograph and size distribution. Next, iPSCs-KCs-Exos were injected subcutaneously around wound sites, and its efficacy was evaluated by measuring wound closure areas, histological examination, and immunohistochemistry staining. The effects of iPSCs-KCs-Exos on proliferation and migration of keratinocytes and endothelial cells in vitro were assessed by EdU staining, wound healing assays, and transwell assay. Then, high-throughput microRNA sequencing was used to explore the underlying mechanisms. We assessed the roles of miR-762 in iPSCs-KCs-Exos-induced regulation of keratinocytes and endothelial cells migration. Furthermore, the target gene which mediated the biological effects of miR-762 in keratinocytes and endothelial cells was also been detected. Results The analysis revealed that iPSCs-KCs-Exos application to the burn wound drove the acceleration of wound closure, with more robust angiogenesis and re-epithelialization being evident. Such iPSCs-KCs-Exos treatment effectively enhanced endothelial cell and keratinocyte migration in vitro. Moreover, the enrichment of miR-762 was detected in iPSCs-KCs-Exos and was found to target promyelocytic leukemia (PML) as a means of regulating cell migration through a mechanism tie to integrin beta1 (ITGB1). Conclusion These results thus provide a foundation for the further study of iPSCs-KCs-Exos as novel cell-free treatments for deep second-degree burns. Graphical Abstract

Research questionThe relationship between serum progesterone (P) and luteinizing hormone (LH) levels on the human chorionic gonadotropin (hCG) trigger day and the clinical pregnancy outcomes in modified natural frozen-thawed embryo transfer (mNC-FET) cycles are controversial.DesignThis was a retrospective study of 788 mNC-FET cycles. A smooth fitting curve and threshold effect analysis was performed to identify the effect of serum P and LH levels measured on the hCG day on the clinical pregnancy rate (CPR) and live birth rate (LBR) of mNC-FET cycles.ResultsThe CPR and LBR decreased significantly when the LH level on the hCG day was greater than or equal to 32 IU/L. Further subgroup analysis showed that the CPR decreased significantly when the P level on the hCG day was equal to or greater than 1 ng/mL. When the P level was lower (< 1 ng/mL), the patients with an LH level greater than or equal to 32 IU/L had reduced CPR and LBR in mNC-FET cycles.ConclusionApplying the hCG trigger on a day with a higher P level (≥ 1 ng/mL) leads to a decreased CPR and LBR. hCG administration with a higher LH level (≥ 32 IU/L) also leads to a decreased CPR and LBR in mNC-FET cycles when the P level is less than 1 ng/mL.

Anterior cruciate ligament deficiency (ACLD) is often accompanied by concomitant meniscal tears. The study aimed to assess the kinematic alterations of patellofemoral joint (PFJ) in anterior cruciate ligament deficiency knees with or without meniscal tears during a single-leg lunge. Sixty unilateral anterior cruciate ligament deficiency patients were recruited for the study, including 15 isolated anterior cruciate ligament deficiency patients (group 1), 15 anterior cruciate ligament deficiency patients with medial meniscal tears (group 2), 15 patients with lateral meniscal tears (group 3) and 15 patients with combined medial/lateral meniscal tears (group 4). The patellofemoral joint kinematics were determined by a single fluoroscopic image system. Patellofemoral joint kinematics of contralateral anterior cruciate ligament-intact (ACLI) and anterior cruciate ligament deficiency knees were compared. With or without meniscal tears, anterior cruciate ligament deficiency knees had significantly smaller patellar flexion than the anterior cruciate ligament-intact knees (∼5°–10°; p < 0.05). anterior cruciate ligament deficiency knees had more patellar lateral tilting by approximately 1°–2° than the anterior cruciate ligament-intact knees (p < 0.05) in groups 2, 3, and 4. anterior cruciate ligament deficiency groups with medial meniscal deficiencies showed consistent increased lateral patellar translations (2–4 mm) compared to the anterior cruciate ligament-intact group during a single-leg lunge. The results indicate that meniscal tears alter anterior cruciate ligament deficiency patients’ patellofemoral joint kinematics and the types of the meniscal injuries also affect the patellofemoral joint kinematics. Considering the varying effects of meniscal tears on the patellofemoral joint kinematics, specific treatments for anterior cruciate ligament deficiency patients with meniscal tears should be proposed in some closed kinetic chain (CKC) exercise programs, such as single-leg lunge.

Abstract Ferroptosis, a recently identified and iron-dependent cell death, differs from other cell death such as apoptosis, necroptosis, pyroptosis, and autophagy-dependent cell death. This form of cell death does not exhibit typical morphological and biochemical characteristics, including cell shrinkage, mitochondrial fragmentation, nuclear condensation. The dysfunction of lipid peroxide clearance, the presence of redox-active iron as well as oxidation of polyunsaturated fatty acid (PUFA)-containing phospholipids are three essential features of ferroptosis. Iron metabolism and lipid peroxidation signaling are increasingly recognized as central mediators of ferroptosis. Ferroptosis plays an important role in the regulation of oxidative stress and inflammatory responses. Accumulating evidence suggests that ferroptosis is implicated in a variety of cardiovascular diseases such as atherosclerosis, stroke, ischemia-reperfusion injury, and heart failure, indicating that targeting ferroptosis will present a novel therapeutic approach against cardiovascular diseases. Here, we provide an overview of the features, process, function, and mechanisms of ferroptosis, and its increasingly connected relevance to oxidative stress, inflammation, and cardiovascular diseases.

Whether load carriage leads to six-degrees-of-freedom (6DOF) knee kinematic alterations remains unclear. Exploring this mechanism may reveal meaningful knee kinematic information that can be used to improve load carriage conditions, the design of protective devices, and the knowledge of the effects of load carriage on knees. We recruited 44 subjects to explore kinematic alterations from an unloaded state to 60% bodyweight (BW) load carriage. A three-dimensional gait analysis system was used to collect the knee kinematic data. One-way repeated analysis of variance (ANOVA) was used to explore the effects of load levels on knee kinematics. The effects of increasing load levels on knee kinematics were smooth with decreased or increased trends. We found that knees significantly exhibited increased lateral tibial translation (up to 1.2 mm), knee flexion angle (up to 1.4°), internal tibial rotation (up to 1.3°), and tibial proximal translation (up to 1.0 mm) when they went from an unloaded state to 60%BW load carriage during the stance phase (p < 0.05). Significant small knee adduction/abduction angle and posterior tibial translation alterations (

ObjectiveTo explore the effectiveness of cryoablation combined with arterial perfusion with programmed cell death protein 1 inhibitors in overcoming immune resistance in advanced solid cancers.MethodsIn this pilot retrospective study, nine patients with solid cancers were treated with tumour cryoablation and arterial perfusion with programmed cell death protein 1 inhibitors, which had previously proven ineffective. The CIBERSORT software was used to estimate the levels of tumour-infiltrating immune cells in the challenged tumour. Changes in the levels of circulating T cells were assessed using flow cytometry. The primary endpoints were disease control and objective response rates, and the secondary endpoint was safety.ResultsThe nine patients with advanced solid tumours received cryoablation combined with arterial perfusion with programmed cell death protein 1 inhibitors between June and December 2021. The median follow-up time was 5.8 months. We recorded an objective response rate in two patients (22.22%). The best overall responses were partial responses in two patients (22.22%) and one case (11.11%) of stable disease, while six patients (66.67%) presented progressive disease. However, the median overall survival time was not reached. The median progression-free survival was 2.4 months. Treatment-related severe adverse events included one case of abdominal infection and one case of upper gastrointestinal bleeding, which were cured after the intervention. The CIBERSORT software confirmed the importance of cryoablation in regulating tumour-infiltrating immune cells. Thus, macrophage polarisation from the M2 to the M1 phenotype in the challenged tumour and a gradual increase in the levels of circulating CD4+ T cells were observed after administration of the combination therapy.ConclusionCryoablation combined with arterial perfusion with programmed cell death protein 1 inhibitors has the potential efficacy and safety to overcome immune resistance in patients with advanced solid cancers. The combination therapy leads to macrophage polarisation from the M2 to the M1 phenotype in the challenged tumour to enhance antitumour immunity.

ObjectivesThis study aimed to investigate the technical methods and safety of artificial pneumothorax and artificial hydrothorax in the treatment of lung cancer adjacent to vital organs by CT-guided microwave ablation.Subjects and MethodsThree of the six patients were men and three were women, with a mean age of 66.0 years (range 47–78 years). There patients had primary pulmonary adenocarcinoma, one had lung metastasis from liver cancer, one had lung metastasis from colon cancer, and one had lung metastasis from bladder cancer. There were four patients with a single lesion, one with two lesions, and one with three lesions. The nine lesions had a mean diameter of 1.1 cm (range 0.4–1.9). In three patients, the lung cancer was adjacent to the heart, and in the remaining three, it was close to the superior mediastinum. Six patients were diagnosed with lung cancers or lung metastases and received radical treatment with microwave ablation (MWA) assisted by artificial pneumothorax and artificial hydrothorax in our hospital. Postoperative complications were observed and recorded; follow-up was followed to evaluate the therapeutic effect.ResultsThe artificial pneumothorax and artificial hydrothorax were successfully created in all six patients. A suitable path for ablation needle insertion was also successfully established, and microwave ablation therapy was carried out. 2 patients developed pneumothorax after operation; no serious complications such as operation-related death, hemothorax, air embolism and infection occurred.Moreover, 4–6 weeks later, an enhanced CT re-examination revealed no local recurrence or metastasis, and the rate of complete ablation was 100%.ConclusionsMicrowave ablation, assisted by artificial pneumothorax, artificial hydrothorax, is a safe and effective minimally invasive method for treating lung cancer adjacent to the vital organs, and optimizing the path of the ablation needle and broadening the indications of the ablation therapy

ObjectiveTo explore the correlation of CT-MRI pathology with lung tumor ablation lesions by comparing CT, MRI, and pathological performance of rabbit lung VX2 tumor after thermal ablation.MethodsThermal ablation including microwave ablation (MWA) and radiofrequency ablation (RFA) was carried out in 12 experimental rabbits with lung VX2 tumors under CT guidance. CT and MRI performance was observed immediately after ablation, and then the rabbits were killed and pathologically examined. The maximum diameter of tumors on CT before ablation, the central hypointense area on T2-weighted image (T2WI) after ablation, and the central hyperintense area on T1-weighted image (T1WI) after ablation and pathological necrosis were measured. Simultaneously, the maximum diameter of ground-glass opacity (GGO) around the lesion on CT after ablation, the surrounding hyperintense area on T2WI after ablation, the surrounding isointense area on T1WI after ablation, and the pathological ablation area were measured, and then the results were compared and analyzed.ResultsAblation zones showed GGO surrounding the original lesion on CT, with a central hypointense and peripheral hyperintense zone on T2WI as well as a central hyperintense and peripheral isointense zone on T1WI. There was statistical significance in the comparison of the maximum diameter of the tumor before ablation with a central hyperintense zone on T1WI after ablation and pathological necrosis. There was also statistical significance in the comparison of the maximum diameter of GGO around the lesion on CT with the surrounding hyperintense zone on T2WI and isointense on T1WI after ablation and pathological ablation zone. There was only one residual tumor abutting the vessel in the RFA group.ConclusionsMRI manifestations of thermal ablation of VX2 tumors in rabbit lungs have certain characteristics with a strong pathological association. CT combined with MRI multimodal radiomics is expected to provide an effective new method for clinical evaluation of the immediate efficacy of thermal ablation of lung tumors.

Abstract Lateral heterostructures of two-dimensional (2D) materials, integrating different phases or materials into a single piece of nanosheet, have attracted intensive research interests for electronic devices. Extending the 2D lateral heterostructures to spintronics demands more diverse electromagnetic properties of 2D materials. In this paper, using density functional theory calculations, we survey all IV, V, and VI group transition metal dichalcogenides (TMDs) and discover that CrS2 has the most diverse electronic and magnetic properties: antiferromagnetic (AFM) metallic 1T phase, non-magnetic (NM) semiconductor 2H phase, and ferromagnetic (FM) semiconductor 1T′ phase with a Curie temperature of ~1000 K. Interestingly, we find that a tensile or compressive strain can turn the 1T′ phase into a spin-up or spin-down half-metal. Such strain tunability can be attributed to the lattice deformation under tensile/compressive strain that selectively promotes the spin-up/spin-down VBM (valence band bottom) orbital interactions. The diverse electromagnetic properties and the strain tunability enable strain-controlled spintronic devices using a single piece of CrS2 nanosheet with improved energy efficiency. As a demo, a prototypical design of the spin-valve logic device is presented. It offers a promising solution to address the challenge of high energy consumption in miniaturized spintronic devices.

Abstract Background It is reported that appropriately 50% of early breast cancer patients with 1–2 positive sentinel lymph node (SLN) micro-metastases could not benefit from axillary lymph node dissection (ALND) or breast-conserving surgery with whole breast irradiation. However, whether patients with 1–2 positive SLN macro-metastases could benefit from ALND remains unknown. The aim of our study was to develop and validate nomograms for assessing axillary non-SLN metastases in patients with 1–2 positive SLN macro-metastases, using their pathological features alone or in combination with STMs. Methods We retrospectively reviewed pathological features and STMs of 1150 early breast cancer patients from two independent cohorts. Best subset regression was used for feature selection and signature building. The risk score of axillary non-SLN metastases was calculated for each patient as a linear combination of selected predictors that were weighted by their respective coefficients. Results The pathology-based nomogram possessed a strong discrimination ability for axillary non-SLN metastases, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.727 (95% CI: 0.682–0.771) in the primary cohort and 0.722 (95% CI: 0.653–0.792) in the validation cohort. The addition of CA 15–3 and CEA can significantly improve the performance of pathology-based nomogram in the primary cohort (AUC: 0.773 (0.732–0.815) vs. 0.727 (0.682–0.771), P

Mediators of insulin signalling are targets of cullin-RING ubiquitin ligases (CRL) that mediate protein degradation, but the role of protein degradation in insulin signalling is incompletely understood. Here, the authors identified a glucose-responsive CRL4-COP1-ETV5 proteolytic axis that promotes insulin secretion, and is inhibited under hypoglycemia.

ObjectivesTo prospectively investigate the feasibility and efficacy of MRI-guided MWA for lung malignant tumor in our single center.Materials and Methods22 patients [mean age, 56.86 ± 13.05(23–73)years] with 23 malignant lung tumors were enrolled in the study. 21 patients had a single lesion and 1 patient had 2 lesions in the ipsilateral lung. The average maximum diameter of the lesion was 1.26 ± 0.65 (0.50-2.58)cm. Percutaneous MWA was guided by 1.5T MRI scanner using a MR-compatible microwave antenna to the target the lung lesions and ablation area was monitored intraoperatively by using a shielded MR-compatible microwave device and then follow-up.ResultsAll patients were successfully treated under MR-guided MWA for lung tumors. Average operation time was 72.21 ± 24.99 (36–158) mins. T2WI signal intensity of the lesion gradually decreased over the course of MWA. The center of the ablated zones showed a short T1 and short T2 signals with the ring-like of long T1 and long T2 signals surrounded after immediately evaluation. No serious complications occurred. The average follow-up period was 12.89 ± 4.33 (2.0-19.6) months. Local recurrence occurred in one patient, representing a technical efficacy of 95.5% (21/22).ConclusionMagnetic resonance-guided microwave ablation for lung malignant tumor was feasible and demonstrated unique advantages in efficacy evaluation.

The burgeoning demand for enhanced power-system safety means that there is increased attention on technologies for the detection and location of cable faults. The double-terminal fault location method, which senses a fault current using a current transformer (CT), is the most effective and widely applied method in industrial practice. However, CT sensors may suffer from magnetic saturation when exposed to a high fault current, resulting in significant location errors, and their sensitivity cannot be adjusted. To address this problem, this paper describes an improved method for the acquisition of fault signal and the identification of fault-wave arrival time in power cables. First, a novel noncontact sensor (NCS) is developed for the detection of electric fields, and its sensitivity-adjustment curves are obtained by theoretical calculation and simulation. Then, based on feedback variational mode decomposition (FVMD) and the Wigner–Ville distribution (WVD), an improved method (the FVMD + WVD method) for the identification of fault-wave arrival time is devised, and its efficacy and accuracy are verified by simulations in Power Systems Computer-Aided Design/Electromagnetic Transients including DC (PSCAD/EMTDC) software. Finally, the fault-wave arrival-time detection performance of the NCS is examined in a series of on-site DC and AC experiments based on damped AC technology. The results show that the NCS exhibits feasible and effective performance, and that its response can be appropriately tuned based on its sensitivity-adjustment curves. The FVMD + WVD method is more accurate than several other current methods, as its error is only 0.48%, and thus this method enables the practical location of cable faults. In sum, these findings demonstrate that the NCS and the FVMD + WVD method comprise an improved system for the detection and location of cable faults, which will enhance cable safety in power systems.

Objective This study aimed to evaluate the clinical safety and efficacy magnetic resonance (MR)-guided percutaneous thermal ablation for the treatment of small liver malignant tumors of segment II and IVa (≤3.0 cm) abutting the heart. Method The enrollment of 24 patients with 25 malignant liver lesions located on the II or IVa segment abutting the heart who underwent MRI-guided thermal ablation between August 2010 and February 2020 were retrospectively analyzed. Follow-up MRI was performed to evaluate the curative effect. Local tumor progression-free survival and overall survival rates were also calculated. Results The procedures including radiofrequency ablation (RFA) for 15 patients and microwave ablation (MWA) for 9 patients were successfully accomplished (technical success rate of 100%) without major complications. The mean duration time was 78.4 ± 29.4 min (40–140 min), and mean follow-up time was 31.5 ± 22.2 months (6–92 months). The technical efficacy was 100% following one ablation session with MRI assessment after one month. Local tumor progression was observed in one patient with a metastatic lesion located in segment II at 18 months follow-up. The progression-free survival time was 20.1 ± 16.9 months (median: 15 months). The 1-, 3-, and 5-year local tumor progression-free survival rates of this patient were 100%, 94.7%, and 94.7%, respectively. With regards to all the patients, the 1-, 3-, and 5-year estimated overall survival rates were 91.7%, 80.6%, and 50.1%, respectively. Conclusion MR-guided thermal ablation is safe and effective for the treatment of small liver malignant tumors located on the II or IVa segment abutting the heart.

Orexin is a neuropeptide that is primarily synthesized and secreted by the lateral hypothalamus (LH) and includes two substances derived from the same precursor (orexin A [OXA] and orexin B [OXB]). Studies have shown that orexin is not only involved in the regulation of eating, the sleep–wake cycle, and energy metabolism, but also closely associated with various physiological functions, such as cardiovascular control, reproduction, stress, reward, addiction, and the modulation of pain transmission. At present, studies that have been performed both domestically and abroad have confirmed that orexin and its receptors are closely associated with pain regulation. In this article, the research progress on acute pain regulation involving orexin is reviewed.

Antibiotics are refractory pollutants that have been widely found in various environmental media such as soil and surface water. Existing sewage treatments perform poorly at preventing antibiotics in urban sewage from polluting natural environments. In this study, we designed a bioelectrically enhanced bioretention cell system (bioretention cell-microbial fuel cell, BRC-MFC) that utilizes the unique structure of the BRC system to improve the removal of sewage antibiotics. This new system can efficiently remove antibiotics by using a synergy of plant absorption, filler adsorption, filler filtration and microbial degradation. To study the influences of multiple-antibiotics stress on the decontamination performance of BRC-MFC, ofloxacin (OFLX) and tetracycline (TC) were selected as target antibiotics, and five BRC-MFCs were built to treat sewage containing antibiotics of different concentrations. The concentrations of pollutant in the influent and effluent were measured and the pollutant removal performance of BRC-MFC was studied. The diversity of rhizosphere microorganisms and the abundance of denitrifying functional genes were analyzed. Experimental results showed that over 90% of OFLX and TC in each BRC-MFC were removed, with the removal rates positively correlating with the concentration of antibiotics. In addition, the removal rates of chemical oxygen demand (COD) in BRC-MFC were both over 90%, while the removal rate of total nitrogen (TN) was around 70%. Meanwhile, antibiotics could significantly improve the removal of ammonia nitrogen (NH4+-N, p < 0.01). The microbial richness decreased, and we found that combined antibiotic stress on microorganisms was stronger than single antibiotic stress. The abundance of denitrifying functional genes was reduced by antibiotic stress. The results of this study provide reference values for other projects focusing on removing various antibiotics from domestic sewage using BRC-MFC.

Organic phosphorus (Po) may play a vital role in phosphorus availability via its mineralization by alkaline phosphatase (ALP), being encoded by phoD gene, in calcareous soil. Understanding the effects of long-term fertilization on the community of phoD harboring bacteria and the related alteration of the P availability owing to the changes in ALP secretion may offer a chance to elucidate the Po contribution to soil available P. Based on a long-term experiment, we analyzed the phoD gene harboring microbial diversity, abundance and composition, ALP and Po forms, and their relationship. The treatments involved were control without any fertilizers (CK), synthetic nitrogen and potassium (NK), synthetic nitrogen, phosphorus and potassium (NPK), NPK and crop stalk return (SNPK), and NPK plus organic manure (MNPK). Fertilization increased the abundance and diversity of phoD gene harboring microbial over CK. Those receiving NPK and NPK treatments integrated with organic supplements significantly improved the relative abundance of Proteobacteria but decreased Gemmatimonadetes at the phylum level, while all fertilized treatments appreciably increased the relative abundance of Lysobacter but decreased that of Gemmatirosa and Afipia, at the genus level. SNPK and MNPK treatments noticeably increased the relative abundance of Methylobacter but reduced Pseudomonas and Streptomyces relative to those receiving synthetic fertilizer treatments. Long-term fertilization markedly raised ALP activity, which was significantly and positively correlated with the relative abundance of the phylum Proteobacteria as represented by the genera Methylobacterium and Lysobacter. ALP was closely associated with moderately labile Po, followed by enzyme P, recalcitrant Po, and labile Po. The changes in phoD bacteria and ALP were mainly driven by soil organic carbon, Olsen P and pH. We concluded that the long-term fertilization, especially the addition of organic supplements, profoundly modified the soil properties and subsequently changed the diversity and relative abundance of phoD gene harboring bacteria, which promoted the activity of ALP, and thus the mineralization of various forms of Po (mainly moderately labile Po) to enhance the P availability.

Lipid was an essential constituent of aquatic feeds, among which fish oil (FO) was the most excellent lipid source for its nutritive values. However, high price and limited production restricted its application, thus leading to the consideration of developing other alternative lipid sources, and soybean oil (SO) instead of FO was applied as the main lipid source in the commercial feed of grass carp. In the present study, two typical lipids sources FO and SO were used to prepare grass carp feed, and their comparative effects on the growth performance, nutrient composition and metabolic signaling were investigated. The growth performance of two groups exhibited no significant difference, while crude lipid was much higher in the muscle of SO group. Additionally, muscle fatty acid composition of both groups were highly correlated with that of diets, and the proportion of muscle n-3 polyunsaturated fatty acids was notably higher in the FO group, especially that of C20:5n-3 (EPA) and C22:6n-3 (DHA). Comparative digital gene expression profiles (DGE) was conducted and 1261 differentially expressed genes (DEGs) had been identified, then gene ontology (GO) enrichment analysis revealed the enriched functional subterms were primarily focused on cellular metabolic processes and regulation. KEGG pathway analysis elucidated the main metabolism related pathways, and DEGs involved in fatty acid elongation, fatty acid metabolism, and glycerolipid metabolism pathways were listed, including elongation of very long chain fatty acids protein 7 (el7), lysophospholipid acyltransferase 4 (lpcat4), long-chain acyl-CoA synthetase (acs), phosphatidate phosphatase LPIN (lpin), cathepsin L, and glucose-6-phosphate isomerase (gpi) et al. In conclusion, the nutritional composition rather than growth performance of grass carp was affected by different lipid sources, and the underlying regulatory signaling was predicted, which would provide theoretical basis for fish diet formulation.

Tetraphenyl porphyrin (TPP) has enormous potential for use as gas chromatography stationary phases because it has a distinctive extended π–π conjugated coplanar structure and a range of interesting properties such as a good solubility in dichloromethane, high melting point, and good thermal stability. In this work, a TPP column was successfully prepared using a static method. The column was nonpolar and had a high efficiency. The chromatographic selectivity of the TPP column was assessed. The TPP column showed superiority retention and higher resolution for alicyclic, aromatic molecules through ring matching and π-π stacking interaction comparable to HP-5MS column. The unique mechanisms through which the TPP column retained polychlorinated biphenyls allowed the peak pair of 2,2ʹ,5-trichlorobiphenyl and 4,4ʹ-dichlorobiphenyl to be resolved better on the TPP column than the HP-5MS column. The TPP column was thermally stable even at 260°C for 2 h and gave results of a high degree of precision (run-to-run and column-to-column) with relative standard deviations

Abstract Background Neuromedin U (NMU) is a neuropeptide belonging to the neuromedin family. Recently, significant associations between NMU and several cancers have been reported. However, no studies have examined the association between NMU and hepatocellular carcinoma (HCC). The purpose of this study was to examine the role of NMU in HCC. Methods An enzyme-linked immunosorbent assay was used to measure the level of NMU protein in the sera of patients with hepatic hemangioma and HCC. NMU and cytokine mRNA expression was assessed in HCC samples via RT-qPCR. A tissue microarray consisting of 228 HCC peri- and intra-tumor tissues was used to detect NMU expression via immunohistochemical analysis. The association between NMU expression and overall survival (OS) and disease-free survival (DFS) was analyzed by Kaplan-Meier curves, the log-rank test, and Cox proportional hazard model. Results The level of NMU protein was increased in the sera of HCC patients (p = 0.006). NMU was expressed in intercellular space, rather than in hepatocytes or HCC cells. The prognosis of HCC patients with high NMU expression in peri-tumor tissue was significantly poorer than that of patients with low NMU expression (OS: p = 0.002, DFS: p = 0.033). Peri-tumor NMU expression was also a significant independent prognostic factor for OS (hazard ratio: 1.541, 95% confidence interval: 1.092–2.175, p = 0.014). The level of NMU expression was positively associated with M2 macrophage percentage and the levels of type-2 inflammatory cytokines in HCC tissue. Conclusions NMU may serve as a novel prognostic biomarker for HCC patients, although further validation is needed in the future. The activation of M2 macrophages and a type-2 inflammatory response may involve in the role of NMU in patients with HCC.

After-sale service is an integrable part of marketing activities. The after-sale service experience of a consumer can be measured by the dynamic maintenance (DM) strategy used by the merchant, i.e., the instantaneous fractions of the maintenance cost paid by the merchant in the total maintenance cost at all time. This paper aims to develop an optimal DM strategy for a word-of-mouth (WOM) marketing campaign. First, we propose an individual-based WOM propagation model in which the effect of the DM strategy is accounted for. Second, we convert the original problem into an optimal control problem, where the objective functional stands for the expected marketing profit, each optimal control stands for an optimal DM strategy. Third, we derive the optimality system for the optimal control problem. By solving the optimality system, we get a potential optimal control. Next, through comparative experiments we conclude that the DM strategy associated with the potential optimal control outperforms most DM strategies in terms of the expected marketing profit. Therefore, we recommend this potential DM strategy. Finally, we examine the effect of some factors on the expected marketing profit for the potential DM strategy. Our findings help to enhance the marketing profit of a WOM marketing campaign.

With the advent of Internet-of-Things (IoT) age, IoT-based distributed denial-of-service (DDoS) attacks have become the mainstream of DDoS attacks. This paper is devoted to exploring the possibility of launching an IoT-based DDoS attack at an extremely low cost. First, a new DDoS attack architecture is proposed. Since the proposed architecture enjoys the advantages of zero management cost, good undetectability, and strong robustness, it is especially suited to resource-limited DDoS attackers. In this architecture and based on a novel botnet growth model, the optimal design of attack strategy is reduced to a variational problem, where the objective functional stands for the estimated expected impact of the DDoS attack associated with a DDoS attack strategy. Finally, the variational problem is resolved for three different types of DDoS defense strategies. This work deepens our understanding of IoT-based DDoS attacks.

Purpose To evaluate the clinical safety and efficacy of percutaneous radiofrequency ablation (RFA) using multitined expandable electrodes under magnetic resonance imaging (MRI) guidance in the treatment of small hepatocellular carcinomas (HCCs) in the hepatic dome. Materials and methods The data of 49 patients with 50 HCC lesions in the hepatic dome who underwent MRI-guided RFA from April 2010 to January 2018 were retrospectively analyzed. Planning, targeting, and controlling were performed under MR-guidance during the procedure. The complications after RFA were observed. Follow-up MRI was performed to evaluate the curative effect. The local progression-free survival, recurrence-free survival, and overall survival rates were calculated using the Kaplan-Meier survival curve. Results The procedures were successfully accomplished in all patients without major complications. The mean follow-up time was 36.9 ± 25.8 months (range, 3–99 months). Technical success was 100% after one RFA session with MRI assessment after 1 month. Local tumor progression was observed in one patient (2%) with the lesion located in the hepatic dome at 4 months on a subsequent follow-up MRI. The progression-free survival time was 25.0 ± 22.7 months (median, 17.0 months). The 1-,3-, and 5-year local tumor progression-free survival rates were all 98.0%. The 1-,3-, and 5-year recurrence-free survival rates were 68.1%, 39.9%, and 28.5%, respectively, and the estimated overall survival rates were 93.7%, 76.3%, and 54.3%, respectively. Conclusion Planning, targeting, and controlling of RFA were well supported by MRI with acceptable time. MRI-guided RFA for small HCCs in the hepatic dome is safe and effective with fewer RF sessions.

Objectives To investigate the feasibility and efficacy of liver-specific magnetic resonance imaging (MRI) with gadolinium-containing contrast agent guidance for microwave ablation (MWA) of recurrent small hepatocellular carcinoma (HCC). Materials and methods The Ethics Committee of the First Affiliated Hospital of Fujian Medical University approved this study. Eighteen patients presented with 30 recurrent small HCCs, at least one lesion per patient was undetectable on unenhanced MRI, but this was clearly demonstrated in the hepatobiliary phase after liver-specific MRI contrast agent administration. Gd-BOPTA (16 cases) or Gd-EOB-DTPA (2 cases) were injected half an hour before the procedure, and MWA was performed by percutaneous puncture of the target lesion with a magnetic resonance-compatible microwave antenna under 1.5 T MRI guidance. Results The technical success rate was 100%. The mean maximum diameter of the lesions was 9.7 ± 2.8 mm (5.0–15.4 mm). The mean follow-up time was 11.6 ± 4.7 months (range, 4–19 months), and no local recurrence was observed. Conclusions MWA of small HCCs guided by enhanced liver-specific MRI contrast agent is a safe and effective technique.

Previous study has confirmed that hsa_circ_0092276 is highly expressed in doxorubicin (DOX)-resistant breast cancer cells, indicating that hsa_circ_0092276 may be involved in regulating the chemotherapy resistance of breast cancer. Here we attempted to investigate the biological role of hsa_circ_0092276 in breast cancer. We first constructed DOX-resistant breast cancer cells (MCF-7/DOX and MDA-MB-468/DOX). The 50% inhibiting concentration of MCF-7/DOX and MDA-MB-468/DOX cells was significantly higher than that of their parental breast cancer cells, MCF-7 and MDA-MB-46. MCF-7/DOX and MDA-MB-468/DOX cells also exhibited an up-regulation of drug resistance-related protein MDR1. Compared with MCF-7 and MDA-MB-46 cells, hsa_circ_0092276 was highly expressed in MCF-7/DOX and MDA-MB-468/DOX cells. Hsa_circ_0092276 overexpression enhanced proliferation and the expression of LC3-II/LC3-I and Beclin-1, and repressed apoptosis of breast cancer cells. The effect of hsa_circ_0092276 up-regulation on breast cancer cells was abolished by 3-methyladenine (autophagy inhibitor). Hsa_circ_0092276 modulated autophagy-related gene 7 (ATG7) expression via sponging miR-384. Hsa_circ_0092276 up-regulation promoted autophagy and proliferation, and repressed apoptosis of breast cancer cells, which was abolished by miR-384 overexpression or ATG7 knockdown. In addition, LV-circ_0092276 transfected MCF-7 cell transplantation promoted autophagy and tumor growth of breast cancer in mice. In conclusion, our data demonstrate that hsa_circ_0092276 promotes autophagy and DOX resistance in breast cancer by regulating miR-348/ATG7 axis. Thus, this article highlights a novel competing endogenous RNA circuitry involved in DOX resistance in breast cancer.

Non-destructive plant growth parameters measurement is an important concern in automatic-seedling transplanting. Recently, several image-based monitoring approaches have been proposed and potentially developed for several agricultural applications. The presented study proposed and developed a RealSense-based machine vision system for the close-shot seedling-lump integrated monitoring. The strategy was based on the close-shot depth information. Further, the point cloud clustering and suitable algorithms were applied to obtain the segmentation of 3D seedling models. In addition, the data processing pipeline was developed to assess the different morphological parameter of 4 different seedling varieties. The experiments were carried out with 4 different seedling varieties (pepper, tomato, cucumber, and lettuce) and trained under different light conditions (light and dark). Moreover, analysis results showed that there was not significantly different (p