ABSTRACT Platinum-based chemotherapy failure represents a significant challenge in the management of ovarian cancer (OC) and contributes to disease recurrence and poor prognosis. Recent studies have shed light on the involvement of the gut microbiota in modulating anticancer treatments. However, the precise underlying mechanisms, by which gut microbiota regulates the response to platinum-based therapy, remain unclear. Here, we investigated the role of gut microbiota on the anticancer response of cisplatin and its underlying mechanisms. Our results demonstrate a substantial improvement in the anticancer efficacy of cisplatin following antibiotic-induced perturbation of the gut microbiota in OC-bearing mice. 16S rRNA sequencing showed a pronounced alteration in the composition of the gut microbiome in the cecum contents following exposure to cisplatin. Through metabolomic analysis, we identified distinct metabolic profiles in the antibiotic-treated group, with a notable enrichment of the gut-derived metabolite 3-methylxanthine in antibiotic-treated mice. Next, we employed a strategy combining transcriptome analysis and chemical–protein interaction network databases. We identified metabolites that shared structural similarity with 3-methylxanthine, which interacted with genes enriched in cancer-related pathways. It is identified that 3-methylxanthinesignificantly enhances the effectiveness of cisplatin by promoting apoptosis both in vivo and in vitro . Importantly, through integrative multiomics analyses, we elucidated the mechanistic basis of this enhanced apoptosis, revealing a dopamine receptor D1-dependent pathway mediated by 3-methylxanthine. This study elucidated the mechanism by which gut-derived metabolite 3-methylxanthine mediated cisplatin-induced apoptosis. Our findings highlight the potential translational significance of 3-methylxanthine as a promising adjuvant in conjunction with cisplatin, aiming to improve treatment outcomes for OC patients. IMPORTANCE The precise correlation between the gut microbiota and the anticancer effect of cisplatin in OC remains inadequately understood. Our investigation has revealed that manipulation of the gut microbiota via the administration of antibiotics amplifies the efficacy of cisplatin through the facilitation of apoptosis in OC-bearing mice. Metabolomic analysis has demonstrated that the cecum content from antibiotic-treated mice exhibits an increase in the levels of 3-methylxanthine, which has been shown to potentially enhance the therapeutic effectiveness of cisplatin by an integrated multiomic analysis. This enhancement appears to be attributable to the promotion of cisplatin-induced apoptosis, with 3-methylxanthine potentially exerting its influence via the dopamine receptor D1-dependent pathway. These findings significantly contribute to our comprehension of the impact of the gut microbiota on the anticancer therapy in OC. Notably, the involvement of 3-methylxanthine suggests its prospective utility as a supplementary component for augmenting treatment outcomes in patients afflicted with ovarian cancer.

IntroductionIn early-stage epithelial ovarian cancer (EOC), how to perform lymphadenectomy to avoid stage migration and achieve reliable targeted excision has not been explored in depth. This study comprehensively considered the stage migration and survival to determine appropriate numbers of examined lymph node (ELN) for early-stage EOC and high-grade serous ovarian cancer (HGSOC).MethodsFrom the Surveillance, Epidemiology, and End Results database, we obtained 10372 EOC cases with stage T1M0 and ELN ≥ 2, including 2849 HGSOC cases. Generalized linear models with multivariable adjustment were used to analyze associations between ELN numbers and lymph node stage migration, survival and positive lymph node (PLN). LOESS regression characterized dynamic trends of above associations followed by Chow test to determine structural breakpoints of ELN numbers. Survival curves were plotted using Kaplan-Meier method.ResultsMore ELNs were associated with more node-positive diseases, more PLNs and better prognosis. ELN structural breakpoints were different in subgroups of early-stage EOC, which for node stage migration or PLN were more than those for improving outcomes. The meaning of ELN structural breakpoint varied with its location and the morphology of LOESS curve. To avoid stage migration, the optimal ELN for early-stage EOC was 29 and the minimal ELN for HGSOC was 24. For better survival, appropriate ELN number were 13 and 8 respectively. More ELNs explained better prognosis only at a certain range.DiscussionNeither too many nor too few numbers of ELN were ideal for early-stage EOC and HGSOC. Excision with appropriate numbers of lymph node draining the affected ovary may be more reasonable than traditional sentinel lymph node resection and systematic lymphadenectomy.

"创新是乡村全面振兴的重要支撑,要坚持把科技特派员制度作为科技创新人才服务乡村振兴的重要工作进一步抓实抓好."科技特派员制度在福建南平首创,在全国范围内推广,20多年来,始终不断发展完善,取得了显著成效.

现代科技与金融行业的结合催生了金融科技，而金融科技不仅重塑了传统金融体系，也改变了金融学的理论基础，拓宽了金融学的研究范畴，重建了金融学教学目标，原有的金融学教学模式已无法满足金融行业发展需求。本文通过分析金融科技对金融领域的影响，分析金融科技引领下金融学教学改革的必要性，针对金融科技引领金融学教学改革存在的问题，提出金融科技引领金融学教学改革的路径，以立足金融科技背景，加快推进金融学教学改革，提高人才培养质量，为金融行业提供有效的人力资源供给，满足金融科技领域发展需求。

Cesarean scar pregnancy (CSP) is a rare form of ectopic pregnancy, which is a long-term complication of cesarean section. Prompt and accurate diagnosis of CSP is important to decrease maternal mobility and mortality. However, it is difficult to make an early detection for CSP complicated with morbidly adherent placenta. Contrast-enhanced ultrasound with the advantage in blood flow imaging is low-cost, time-saving, safe and more accessible in clinical practice. Here, we report a case with early detection of CSP with placenta increta by contrast-enhanced ultrasound and its successful uterine-sparing surgical management.

PURPOSE:It is unclear whether vitamin D provides any benefit against the pro-inflammatory effects of homocysteine in elderly patients with type 2 diabetes mellitus (T2DM). METHODS:We compared lymphocyte counts for CD3, CD19, CD4, and CD8 subsets between elderly (age ≥65 years) T2DM patients (n = 5098) and nondiabetes control subjects (n = 20,590) based on the serum concentrations of homocysteine and total vitamin D (calcidiol + calcifediol [total vitamin D, TVD]; <20, 20-30, and >30 ng/mL). FINDINGS:Significant variation in CD19 (P = 0.019), CD4 (P = 0.015), and CD8 (P < 0.001) were associated with serum TVD in T2DM patients with homocysteine ≤15 μmol/L, whereas CD3 (P = 0.003) and CD8 (P = 0.019) varied in control subjects with homocysteine ≤15 μmol/L. In T2DM patients with high homocysteine (>15 μmol/L) levels, significant variation based on serum TVD occurred in CD19 only (P = 0.024), whereas CD3 (P = 0.016) and CD4 (P = 0.001) varied in control subjects with high homocysteine concentrations. IMPLICATIONS:Serum TVD influences variation in CD3, CD19, CD4, and CD8 lymphocyte subsets based on the serum homocysteine concentration in elderly T2DM patients and nondiabetic individuals with moderate to high homocysteine concentrations. The effect of TVD is partially attenuated in individuals with high homocysteine concentrations, with greater attenuation occurring in patients with T2DM. Differences in the variation of lymphocyte subsets between nondiabetes subjects with moderate homocysteine concentrations and those with high homocysteine concentrations constitute a shift from CD8-positive cells to CD4-positive cells, suggesting a change in TH1/TH2 balance based on TVD and homocysteine concentrations that is absent in diabetes cases with high homocysteine concentrations.

为了在不改变载波体制的情况下,提升传统单载波(Single Carrier,SC)和多载波系统(Multi-Carrier,MC)的抗衰落能力,本文利用广义混合载波(Generalized Hybrid Carrier,GHC)系统在信号设计方面的高灵活性,提出基于广义加权分数傅里叶变换(Generalized Weighted Fractional Fourier Transform,GWFRFT)的两分量组合抗衰落方案.针对SC系统,所提两分量方案包含时域和时域反转两个分量,可以有效提升系统抗时间选择性衰落的能力;针对MC系统,所提两分量方案由频域和频域反转两个分量组成,能够有效提升系统抗频率选择性衰落的能力.为了充分挖掘两分量组合信号的潜力,本文对这种信号形式获得性能优势的机理进行了分析.分析结果表明,两分量之间的功率分配和同一符号在两分量中所经历衰落的独立性是影响两分量信号性能的关键因素.鉴于此,本文提出两分量等功率设计和半码块反转方案,进一步优化了两分量组合信号的性能.在此基础上,本文给出两分量组合信号生成方法,并分析其实现复杂度和频谱特性.仿真结果表明,两分量组合方案可以在不占用额外时间和频谱资源的前提下,实现对传统SC和MC系统抗衰落性能的有效提升,而基于分量等功率分配和半码块反转的优化可以进一步增强这种性能提升的效果.

Background: Long non-coding RNA (lncRNA) nuclear enriched abundant transcript 1 (NEAT1) has been documented to implicate in diverse tumor progression. However, the mechanism of NEAT1 in glioma was rarely reported. Methods: The levels of NEAT1, microRNA-152-3p (miR-152-3p) and chaperonin containing TCP1 subunit 6A (CCT6A) in glioma tissues and cells were measured by quantitative real-time polymerase chain reaction (qRTPCR). The cell viability, apoptotic rate, the migrated and invaded abilities of A172 and U251 cells were evaluated via cell counting kit-8 (CCK-8), flow cytometry and Transwell assay, respectively. The mice xenograft model was constructed to further verify the effect of NEAT1. The interactions between miR-152-3p and NEAT1 or CCT6A were predicted by starBase v2.0 or TargetScan, then luciferase reporter assay, RNA immunoprecipitation (RIP) and RNA pull-down assay were performed to validate the interaction. The protein level of CCT6A was detected by Western blot assay. Results: The levels of NEAT1, CCT6A were highly expressed, but miR-152-3p was decreased in glioma tissues and cells. NEAT1 depletion or miR-152-3p mimics suppressed cell viability, migrated and invaded abilities but induced apoptotic rate in A172 and U251 cells, while the introduction of CCT6A partly counteracted these impacts. In addition, NEAT1 silencing impeded xenograft tumor growth in vivo. MiR-152-3p was verified as a direct target of NEAT1 and directly targeted CCT6A. CCT6A expression was upregulated by NEAT1 and reversed by miR-152-3p. Conclusion: NEAT1 enhanced glioma progression, partially through miR-152-3p/CCT6A pathway. The novel regulatory network might contribute to the diagnosis and treatment of glioma.

AimsTo investigate the diabetes-protective effect and weight-lowering potential of a novel long-acting triagonist at three metabolically related hormone receptors including glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), glucagon receptors.Main methodsTriagonist were designed in an iterative manner from native GLP-1, GIP and Glucogan. Main peptide chain (termed TG peptides) and subsequently modified LTG peptides were synthesized via solid phase synthesis. In vitro receptor activity assay was performed to screen the TG peptide with most balanced potency on all three receptors. The in vitro biological activities of modified TG peptides were further investigated by albumin-binding measurement and proteolytic cleavage test. Subsequently, oral glucose tolerance test (OGTT), pharmacokinetic test and chronic study were subjected to the acute and long-term efficacy evaluation of selected fusion peptide, LTG-6.Key findingsTG-8 exhibited equally aligned constituent efficacy and supraphysiological potency on corresponding receptor without cross-reactivity. Modified TG-8, termed LTG-6, exerted the great binding affinity for human serum albumin and the enhanced rational controlled-release of TG-8 in vitro. Further OGTT in different gene knockout mice and diabetic mice demonstrated the promising hypoglycemic and insulinotropic abilities of LTG-6. After long-term treatment for 8 weeks, LTG-6 was proved superior to co-agonists to decrease the body weight and %HbA1c, improve reverse dyslipidemia and glycemic control in the DIO models.SignificanceLTG-6, as a newly designed long-acting triagonist, holds potential to correct the obesity related metabolic disorders.

We identify multi-wavelength counterparts to 1147 submillimeter sources from the S2COSMOS SCUBA-2 survey of the COSMOS field by employing a recently developed radio+machine-learning method trained on a large sample of Atacama Large Millimeter/submillimeter Array (ALMA)–identified submillimeter galaxies (SMGs), including 260 SMGs identified in the AS2COSMOS pilot survey. In total, we identify 1222 optical/near-infrared (NIR)/radio counterparts to the 897 S2COSMOS submillimeter sources with S850 > 1.6 mJy, yielding an overall identification rate of (78 ± 9)%. We find that (22 ± 5)% of S2COSMOS sources have multiple identified counterparts. We estimate that roughly 27% of these multiple counterparts within the same SCUBA-2 error circles very likely arise from physically associated galaxies rather than line-of-sight projections by chance. The photometric redshift of our radio+machine-learning-identified SMGs ranges from z = 0.2 to 5.7 and peaks at z = 2.3 ± 0.1. The AGN fraction of our sample is (19 ± 4)%, which is consistent with that of ALMA SMGs in the literature. Comparing with radio/NIR-detected field galaxy population in the COSMOS field, our radio+machine-learning-identified counterparts of SMGs have the highest star formation rates and stellar masses. These characteristics suggest that our identified counterparts of S2COSMOS sources are a representative sample of SMGs at z ≲ 3. We employ our machine-learning technique to the whole COSMOS field and identified 6877 potential SMGs, most of which are expected to have submillimeter emission fainter than the confusion limit of our S2COSMOS surveys ( mJy). We study the clustering properties of SMGs based on this statistically large sample, finding that they reside in high-mass dark matter halos ((1.2 ± 0.3) × 1013 h−1 ), which suggests that SMGs may be the progenitors of massive ellipticals we see in the local universe.

本文中,我们系统地表述一种自洽的宇宙学模型分析及其参数估计方法,并将其用于Ia型超新星（SNIa）光度距离作为宇宙学标准烛光的研究.我们利用贝叶斯图论方法及其与随机变量间因果性、信息流和概率独立性的对应关系构建我们的分析,并通过实例展示如何在宇宙学数据分析中恰当地运用联合光变曲线分析（JLA） SNIa数据集合中依赖于参数的协方差矩阵.我们的方法从概念到产出的结果均不同于传统的分析方法.可以证明,通常形如χ~2最小化的传统分析等效于施加在SNIa标准化模型变量先验分布上的隐含失真.通过显性地指明这一失真的形式,我们指出它无论从天体物理还是统计

Objective: In order to investigate the effect of secretagogin (SCGN) on colorectal cancer (CRC) cells apoptosis, invasion and migration in vitro. Methods: Expression of SCGN in CRC tissues and the paired adjacent non-tumorous tissues (n = 36) and four human CRC cell lines (HT29, HCT116, SW480 and SW620) were detected. SW480 cells were transfected with the SCGN overexpression plasmid (eGFP-SCGN), si-SCGN-773, and the corresponding negative controls (NCs). Then, cell-cycle distribution, cell apoptosis, migration, invasion and expression of apoptosis-and metastasis-related proteins were detected. Results: SCGN was significantly downregulated in CRC tissues as compared with the adjacent non-tumorous tissues. The expression of SCGN in HT29 and SW480 cells were lower than those in HT116 and SW620 cells. We transfected SW480 cells with SCGN overexpression plasmid eGFP-SCGN and found the increased cell apoptosis, with cell arresting at G0/G1 phase. SW480 cells with SCGN overexpression showed wider wound width and fewer invaded cells than control and blank cells, with upregulated Bax, cleaved Caspase 3 and E-cadherin, and downregulated Bcl-2 and Vimentin. We also transfected SW480 cells with si-SCGN-773 and found si-SCGN increased cell migration and invasion, but did not affect cell apoptosis and expression of related proteins. Conclusion: We concluded that the overexpression of SCGN in SW480 cells promoted cell apoptosis and inhibited cell migration and invasion.

We test the distance-duality relation eta equivalent to d(L) [(1 + z)(2)d(A)] = 1 between cosmological luminosity distance (d(L)) from the JLA SNe Ia compilation and angular-diameter distance (d(A)) based on Baryon Oscillation Spectroscopic Survey (BOSS) and WiggleZ baryon acoustic oscillation measurements. The d(L) measurements are matched to d(A) redshift by a statistically consistent compression procedure. With Monte Carlo methods, nontrivial and correlated distributions of. can be explored in a straightforward manner without resorting to a particular evolution template eta(z). Assuming independent constraints on cosmological parameters that are necessary to obtain d(L) and d(A) values, we find 9% constraints consistent with eta = 1 from the analysis of SNIa + BOSS and an 18% bound results from SNIa + WiggleZ. These results are contrary to previous claims that eta < 1 has been found close to or above the 1 sigma level. We discuss the effect of different cosmological parameter inputs and the use of the apparent deviation from distance-duality as a proxy of systematic effects on cosmic distance measurements. The results suggest possible systematic overestimation of SNIa luminosity distances compared with d(A) data when a Planck Lambda CDM cosmological parameter inference is used to enhance the precision. If interpreted as an extinction correction due to a gray dust component, the effect is broadly consistent with independent observational constraints.

The primarily metabolic abnormality in type 2 diabetes mellitus (T2DM) is the defect in gluconeogenesis and glucose uptake. Itraconazole (ITCZ) is a traditional azole drug with anti-fungal and anticancer properties. However, limited attention has been directed towards the contribution of ITCZ to hepatic gluconeogenesis and glucose uptake in T2DM. The present study aimed to investigate the potential effects of ITCZ on hepatic gluconeogenesis and glucose uptake as well as the underlying mechanisms. No obvious change in cell viability was detected by MTT assay in HepG2 cells with ITCZ treatment at gradually increasing concentrations. Western blot analysis demonstrated that the phosphorylation level of 5' adenosine monophosphate-activated protein kinase (AMPK) was significantly elevated by ITCZ treatment at ≥5 µg/ml (P<0.05). Moreover, ITCZ repressed the gluconeogenesis of HepG2 cells, as evidenced by the dose-dependently increased glycogen synthase kinase 3β phosphorylation level and a notably decreased glucose production rate (P<0.05). Simultaneously, the expression of peroxisome proliferator-activated receptor γ co-activator 1α, phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) in HepG2 cells was reduced by ITCZ in a dose-dependent manner (P<0.001). Furthermore, a 2-deoxyglucose uptake assay revealed that the glucose uptake of HepG2 cells was notably enhanced, accompanied by the ITCZ dose-dependent upregulation of glucose transporter-4 (GLUT-4) (P<0.05). Conversely, silencing of AMPK by small interfering RNA resulted in an increase of ITCZ-reduced gluconeogenesis and inhibition of ITCZ-induced glucose uptake with relative upregulation of PEPCK and G6Pase and downregulation of GLUT4 in the presence of 50 µg/ml ITCZ (P<0.05). Overall, the results indicated that AMPK has an important role in regulating ITCZ-induced glucose uptake by stimulating GLUT4 in HepG2 cells. Therefore, ITCZ may become a promising candidate for T2DM therapy.

1,5-anhydroglucitol (1,5-AG), uric acid and urinary proteins are excreted into the urine with increasing glucosuria. In the present retrospective study we analyzed whether these factors could be used as indicators for type 2 diabetes mellitus (T2DM) glucose control in 6,766 (T2DM) patients. There were 3,988 cases (58.9%) with HbA1c ≤ 6.5%, 853 cases (12.61%) with HbA1c levels ranging from 6.5% to 7% and 1,925 cases (28.5%) with HbA1c > 7%. HbA1c percentages were correlated with age, MA and 1,5-AG serum concentrations ( P < 0.001). The serum uric acid concentration ( P < 0.001) was significantly lower in elevated MA ( P < 0.001) and 24-hour urinary protein ( P = 0.024) patients. Hb1Ac percentages ( P < 0.001) were significantly enhanced in patients with 1,5-AG serum concentrations ≤10 mg/L compared to >10 mg/L. With a derived receiver operating characteristic (ROC) curve, a 1,5-AG cut-off value of 11.55 mg/L for hyperglycemia could be diagnosed with a specificity of 71.2 (69.7–72.6) and a sensitivity of 75.3 (73.6–76.9). The serum 1,5-AG concentration is a marker for hyperglycemia and may be particularly useful as an indicator for short-term glycemic excursions in order to improve treatments in T2DM patients.

为了提升光伏阵列的输出效率,设计了一种以复杂可编程逻辑器件(CPLD)为核心,基于MSP430F169单片机的光伏数据采集系统.针对传统的数据采集方式速度慢、外围电路复杂、安全性低的问题,开发设计了基于CPLD的光伏发电数据采集系统,并且内部采用了先进的先入先出队列(FIFO)存储结构.通过RS232串口方式和无线模块方式与上位机通信传输.实验证明,本设计数据采集速度快、功耗低、传输稳定可靠.

Bayesian graphical models are an efficient tool for modelling complex data and derive self-consistent expressions of the posterior distribution of model parameters. We apply Bayesian graphs to perform statistical analyses of Type Ia supernova (SN Ia) luminosity distance measurements from the joint light-curve analysis (JLA) data set. In contrast to the chi(2) approach used in previous studies, the Bayesian inference allows us to fully account for the standard-candle parameter dependence of the data covariance matrix. Comparing with chi(2) analysis results, we find a systematic offset of the marginal model parameter bounds. We demonstrate that the bias is statistically significant in the case of the SN Ia standardization parameters with a maximal 6s shift of the SN light-curve colour correction. In addition, we find that the evidence for a host galaxy correction is now only 2.4s. Systematic offsets on the cosmological parameters remain small, but may increase by combining constraints from complementary cosmological probes. The bias of the chi(2) analysis is due to neglecting the parameter-dependent log-determinant of the data covariance, which gives more statistical weight to larger values of the standardization parameters. We find a similar effect on compressed distance modulus data. To this end, we implement a fully consistent compression method of the JLA data set that uses a Gaussian approximation of the posterior distribution for fast generation of compressed data. Overall, the results of our analysis emphasize the need for a fully consistent Bayesian statistical approach in the analysis of future large SN Ia data sets.

Robots that work in the wild envi-ronment with heavy load usually use a hydraulic system as its actuator.Considering the structure and control characteristic of the robot,the charac-teristic of single rod hydraulic system on P Q valve is studied.By establishing and using the sys-tem’s nonlinear model and with the characteristic of the P Q valve in mind,this paper analyzes the closed position loop stiffness of the system.The result shows that the equivalent stiffness is propor-tional to the gain of the system when the system is in closed loop condition with external force dis-turbance and this provides a theoretical basis for the control of the legged robot and the analysis of the characteristic of the robot.

Using the longitudinal expression of Hubble expansion rate for the general Lemitre-Tolman-Bondi (LTB) metric as a function of cosmic time, we examine the scale on which the Copernican principle holds in the context of a void model. By way of performing parameter estimation on the constrained Garcia-Bellido-Haugbolle void model, we show that the Hubble parameter data favors a void with a characteristic radius of 2-3 Gpc. This brings the void model closer, but not yet enough, to harmony with observational indications given by the background kinetic Sunyaev-Zel'dovich effect and the normalization of near-infrared galaxy luminosity function. However, the test of such void models may ultimately lie in the future detection of the discrepancy between longitudinal and transverse expansion rates, a touchstone of inhomogeneous models. With the proliferation of observational Hubble parameter data and future large-scale structure observation, a definitive test could be performed on the question of cosmic homogeneity. Particularly, the spherical LTB void models have been ruled out, but more general nonspherical inhomogeneities still need to be tested by observation. In this paper, we utilize a spherical void model to provide guidelines into how observational tests may be done with more general models in the future.

OBJECTIVE:To investigate whether inhibitors of dipeptidyl peptidase-4 (DPP-4) can suppress the atherosclerotic development in diabetic patients.METHODS:The prospective study was carried out in the Out-patient Department of XuHui Central Hospital, Shanghai, China, between March and August 2013. The correlation of major index of glucose and lipid metabolism profiles, and the arterial stiffness index (AI) between diabetic patients and healthy subjects were analyzed.PATIENTS OR MATERIALS:39 patients with type 2 diabetes and 29 healthy subjects were enrolled for measurements of blood glucose, plasma insulin, HbA1c, TC, cholesterol, HDL, AI and body mass index (BMI).RESULTS:Significant differences were found between DPP-4 and blood glucose (fasting and 2 h postprandial), HbA1c, cholesterol, high density lipoprotein and arterial stiffness in normal subjects and diabetic patients. Only the fasting insulin concentration and high density lipoprotein had a significant impact on DPP-4 levels.CONCLUSIONS:It was clear that insulin (fasting) and HDL levels had an impact on DPP-4 activity but only in patients with Type 2 diabetes. The arterial stiffness index was not correlated with DPP-4 levels in Type 2 diabetic patients.