可交联氟化氮杂环聚芳醚的合成及性能

以4-(4-羟基苯基)-2,3-二氮杂萘酮-1-酮(DHPZ)、双酚AF(6F-BPA)、五氟苯乙烯(FSt)和十氟联苯(DFBP)为原料,通过溶液缩聚反应合成了可交联的FSt-FPPE,所得共聚物的结构通过红外光谱和核磁共振确认与设计一致。FStFPPE呈无定形结构,可溶解在N-甲基吡咯烷酮、N,N-二甲基乙酰胺、N,N-二甲基甲酰胺、氯仿、四氢呋喃等有机溶剂中。与交联剂三聚氰酸三烯丙酯(TAC)进行共固化后,聚合物的玻璃化转变温度由235℃提升至255℃。氮气下热分解温度达497℃,800℃时残碳率为53%。固化后聚合物薄膜的拉伸强度为60~67 MPa,拉伸模量为1.05~1.23GPa,断裂伸长率为10%~12%。当TAC含量为1%时,拉伸强度达到最大值67MPa。在介电性能上,固化后介电常数降低,在10MHz~1GHz的频率下,介电常数在2.4~3.0之间。当TAC含量为3%时,介电常数达到最低值2.4。这些结果表明,FSt-FPPE具有优异的综合性能,在微电子领域中具有一定应用价值。

Tumor microenvironment in pancreatic ductal adenocarcinoma:Implications in immunotherapy

Pancreatic ductal adenocarcinoma is one of the most aggressive and lethal cancers.Surgical resection is the only curable treatment option,but it is available for only a small fraction of patients at the time of diagnosis.With current therapeutic regimens,the average 5-year survival rate is less than 10%in pancreatic cancer patients.Immunotherapy has emerged as one of the most promising treatment options for multiple solid tumors of advanced stage.However,its clinical efficacy is suboptimal in most clinical trials on pancreatic cancer.Current studies have suggested that the tumor microenvironment is likely the underlying barrier affecting immunotherapy drug efficacy in pancreatic cancer.In this review,we discuss the role of the tumor microenvironment in pancreatic cancer and the latest advances in immunotherapy on pancreatic cancer.

By Sector Water Consumption and Related Economy Analysis Integrated Model and Its Application in Hai River Basin, China

This paper established a by sector water consumption and economy analysis integrated model with input–output analysis method. The model can be used to identify the relationships between economic activities and the direct water consumption, the total water consumption and the intersectoral water transaction for detailed sectors in regional economy. The method is applied to Hai River Basin in China that is characterized by water shortage. The results found that in Hai River Basin, agriculture sector is responsible for 81.2% of the direct total water consumption in the region, but industrial and service sectors account for 53.2% of the indirect total water consumption. To 24 industrial and service sectors, their ratios of indirect water consumption to total water consumption belong to [90%, 99%]. To per unit output, water consumption intensity was highest in agriculture sector 1 at 96.91 m3 per thousand Yuan, the value of 28 industrial and service sectors were smaller than 1. Products of sector 1, sector 24, sector 3, sector 12, sector 6, sector 11 and sector 10 are the main suppliers of indirect water.

Validation of American Joint Committee on Cancer 8th edition of TNM staging in resected distal pancreatic cancer

BACKGROUND In order to improve risk stratification and clinical management of the pancreatic ductal adenocarcinoma(PDAC),the American Joint Committee on Cancer(AJCC)has published its eighth edition staging manual.Some major changes have been introduced in the new staging system for both T and N categories.Given the rarity of resectable disease,distal pancreatic cancer is likely underrepresented in the published clinical studies,and how the impact of the staging system actually reflects on to clinical outcomes remain unclear.AIM To validate the AJCC 8th edition of TNM staging in distal PDAC.METHODS A retrospective cohort study was performed in seven academic medical centers in the United States.Clinicopathological prognostic factors associated with progression-free survival(PFS)and overall survival(OS)were evaluated through univariate and multivariate analyses.RESULTS Overall,454 patients were enrolled in the study,and were divided into 2 subgroups:Invasive intraductal papillary mucinous neoplasms(IPMN)(115 cases)and non-IPMN associated adenocarcinoma(339 cases).Compared to invasive IPMN,non-IPMN associated adenocarcinomas are more common in relatively younger patients,have larger tumor size,are more likely to have positive lymph nodes,and are associated with a higher tumor(T)stage and nodal(N)stage,lymphovascular invasion,perineural invasion,tumor recurrence,and a worse PFS and OS.The cohort was predominantly categorized as stage 3 per AJCC 7th edition staging manual,and it’s more evenly distributed based on 8th edition staging manual.T and N staging of both 7th and 8th edition sufficiently stratify PFS and OS in the entire cohort,although dividing into N1 and N2 according to the 8th edition does not show additional stratification.For PDAC arising in IPMN,T staging of the 7th edition and N1/N2 staging of the 8th edition appear to further stratify PFS and OS.For PDAC without an IPMN component,T staging from both versions fails to stratify PFS and OS.CONCLUSION The AJCC 8th edition TNM staging system provides even distribution for the T staging,however,it does not provide better risk stratification than previous staging system for distal pancreatic cancer.

Microscopic colitis: Is it a spectrum of inflammatory bowel disease?

Lymphocytic and collagenous colitis are forms of microscopic colitis which typically presents in elderly patients as chronic watery diarrhea. The association between microscopic colitis and inflammatory bowel disease is weak and unclear. Lymphocytic colitis progressing to ulcerative colitis has been previously reported; however there is limited data on ulcerative colitis evolving into microscopic (lymphocytic or collagenous) colitis. We report a series of six patients with documented ulcerative colitis who subsequently were diagnosed with collagenous colitis or lymphocytic colitis suggesting microscopic colitis could be a part of the spectrum of inflammatory bowel disease. The median duration of ulcerative colitis prior to being diagnosed with microscopic colitis was 15 years. We noted complete histological and/or symptomatic remission in three out of six cases while the other three patients reverted back into ulcerative colitis suggesting lymphocytic or collagenous colitis could present as a continuum of ulcerative colitis. The exact molecular mechanism of this histological transformation or the prognostic implications is still unclear. Till then it might be prudent to follow up these patients to assess for the relapse of inflammatory bowel disease as well as for dysplasia surveillance.

Discrimination of cervical cancer cells via cognition-based features

Computer-assisted cervical screening is an effective method to save the doctors'workload and improve their work efficiency.Usually,the correct classification of cervical cells depends on the nuclear segmentation effect and the extraction of nuclear features.However,the precise nucleus segmentation remains a huge challenge,especially for densely distributed nucleus.Moreover,previous cellular classification methods are mostly based on morphological features of nucleus size or color.Those individual features can make accurate classification for severe lesions,but not for mild lesions.In this paper,we propose an accurate instance segmentation algorithm and propose cognition-based features to identify cervical cancer cells.Different from previous individual nucleus features,we also propose population features and cognition-based features according to the Bethesda System(TBS)for reporting cervical cytology and the diagnostic experience of the cytologists.The results showed that the segmentation achieves better success in complex situa-tions than that by traditional segmentation algorithms.Besides,the cell classification via cog-nition-based features also help us find out more about less severe lesions'nuclei than that based on conventional features of individual nucleus,meaning an improvement of classification accu-racy for cervical screening.

OBSERVING NEURONAL ACTIVITIES WITH RANDOM ACCESS TWO-PHOTON MICROSCOPE

As a second messenger in signal transduction,calcium ion plays a very important role in neuronal information processing and integrating.Limited by the imaging technique,it is difficult to simultaneously perform deep tissue imaging and measure intracellular free calcium concentration([Ca^(2+)]i)in different compartments of neurons in brain slice noncollinearly.By means of random access two-photon microscopy,which provides high optical penetration into tissues and low photo damage,we successfully measured[Ca^(2+)]i of different parts of pyramidal neurons in neocortical layer V in rat brain slices with high spatial and temporal resolution.Combining the patch clamp technique,we stimulated the soma with depolarizing current and explored the dynamics of calcium in pyramidal neurons.

How Do Young Children Manage Their Reputation among Peers?

Young children’s reputation management is closely related to their social development.The purpose of our study is to examine the interaction between theory of mind and partner choice on children’s reputation management.Participants consisted of 270 children who were 3 to 5 years old.First,we measured participants’theory of mind capabilities using the unexpected location task and unexpected content task and then randomly divided the participants into the control group,non-partner–choice group,and partner-choice group.We measured reputation management by comparing children’s willingness to share and sharing behavior between these groups.Thefindings are as follows:(1)Children from ages 3 to 5 demonstrated reputation management,and their reputation management followed a significant developmental trend.The reputation management of 4-to 5-year-old children was significantly better than that of 3-year-old children.(2)Scores on the theory of mind tasks positively predicted children’s reputation management.(3)Partner choice affected children’s reputation management.In the partner-choice group,children’s reputation management was more apparent.(4)Partner choice did moderate the relationship between theory of mind and children’s reputation management.In the partner-choice group,theory of mind had a stronger predictive effect on children’s reputation management.

Regulating Empathy: Exploring the Process through Agents and Strategies

Empathy is a complex emotional phenomenon that plays a crucial role in promoting cooperation and social cohesion within human society.However,there is ongoing debate regarding the mechanisms that underlie the generation of empathy.While the importance of biological emotional resonance in empathy is widely recognized,the influence of cognitive regulation on empathetic responses cannot be disregarded.This article seeks to review the agents and strategies involved in regulating empathy to construct a dynamic model depicting the process.The model highlights that the impact of specific goals on empathy regulation is not definitive;rather,it depends on an individual’s interpretation and pursuit of goals,which can either enhance or hinder empathy.To effectively regulate empathy,individuals employ various emotion regulation strategies,the effectiveness and frequency of which can vary depending on individual and contextual factors.This context provides a specific pathway for understanding the generation of empathy.Further research should be conducted to systematically investigate the regulatory mechanisms of empathy by integrating contextual factors and individual characteristics.Furthermore,it is incredibly important to enhance the impact of empathy on social interactions by utilizing its ability to be controlled for intervention and prediction purposes.

Potential and challenges of tannins as an alternative to in-feed antibiotics for farm animal production

Naturally occurring plant compounds including tannins, saponins and essential oils are extensively assessed as natural alternatives to in-feed antibiotics.Tannins are a group of polyphenolic compounds that are widely present in plant region and possess various biological activities including antimicrobial,anti-parasitic, anti-viral, antioxidant, anti-inflammatory, immunomodulation, etc.Therefore, tannins are the major research subject in developing natural alternative to in-feed antibiotics.Strong protein affinity is the well-recognized property of plant tannins, which has successfully been applied to ruminant nutrition to decrease protein degradation in the rumen, and thereby improve protein utilization and animal production efficiency.Incorporations of tannin-containing forage in ruminant diets to control animal pasture bloat, intestinal parasite and pathogenic bacteria load are another 3 important applications of tannins in ruminant animals.Tannins have traditionally been regarded as "anti-nutritional factor" for monogastric animals and poultry, but recent researches have revealed some of them, when applied in appropriate manner, improved intestinal microbial ecosystem, enhanced gut health and hence increased productive performance.The applicability of plant tannins as an alternative to in-feed antibiotics depends on many factors that contribute to the great variability in their observed efficacies.

Histological evaluation in ulcerative colitis

This review summarizes diagnostic problems,challenges and advances in ulcerative colitis(UC).It emphasizes that,although histopathological examination plays a major role in the diagnosis and management of UC,it should always be interpreted in the context of clinical,endoscopic,and radiological findings.Accurate diagnosis requires knowledge of the classic morphological features of UC,as well as a number of atypical pathological presentations that may cause mis-classification of the disease process,either in resection or biopsy specimens.These atypical pathological presentations include rectal sparing and patchiness of disease at initial presentation of UC in pediatric patients or in the setting of medically treated UC,cecal or ascending colon inflammation in left-sided UC,and backwash ileitis in patients with severe ulcerative pancolitis.Loosely formed microgranulomas,with pale foamy histiocytes adjacent to a damaged crypt or eroded surface,should not be interpreted as evidence of Crohn’s disease.Indeterminate colitis should only be used in colectomy specimens as a provisional pathological diagnosis.Patients with UC are at risk for the development of dysplasia and carcinoma;optimal outcomes in UC surveillance programs require familiarity with the diagnostic criteria and challenges relating to UC-associated dysplasia and malignancy.Colon biopsy from UC patients should always be evaluated for dysplasia based on cytological and architectural abnormalities.Accurate interpretation and classification of dysplasia in colon biopsy from UC patients as sporadic adenoma or UC-related dysplasia[flat,adenoma-like,or dysplasia-associated lesion or mass(DALM)]requires clinical and endoscopic correlation.Isolated polypoid dysplastic lesions are considered to be sporadic adenoma if occurring outside areas of histologically proven colitis,or adenoma-like dysplasia if occurring in the diseased segment.Recent data suggest that such lesions may be treated adequately by polypectomy in the absence of flat dysplasia in the patient.UC patients with DALM or flat high-grade dysplasia should be treated by colectomy because of the high probability of adenocarcinoma.The natural history of low-grade dysplasia(LGD)is more controversial:while multifocal LGD,particularly if detected at the time of initial endoscopic examination,is treated with colectomy,unifocal flat LGD detected during surveillance may be managed by close follow-up with increased surveillance.The surveillance interval and treatment options for UC patients with dysplasia are reviewed in detail.

Nodal Promotes mir206 Expression to Control Convergence and Extension Movements During Zebrafish Gastrulation

Nodal, a member of the transforming growth factor β （TGF-β） superfamily, has been shown to play a role in mesendoderm induction and gastrulation movements. The activity of Nodal signaling can be modulated by microRNAs （miRNAs） as previously reported, but little is known about which miRNAs are regulated by Nodal during gastrulation. In the present study, we found that the expression of mir206, one of the most abundant miRNAs during zebrafish early embryo development, is regulated by Nodal signaling. Abrogation of Nodal signal activity results in defective convergence and extension （CE） movements, and these cell migration defects can be rescued by supplying an excess of mir206, suggesting that mir206 acts downstream of Nodal signaling to regulate CE movements. Furthermore, in mir206 morphants, the expression of cell adhesion molecule E-cadherin is significantly increased, while the key transcriptional repressor of E-cadherin, snailla, is depressed. Our study uncovers a novel mechanism by which Nodal-regulated mir206 modulates gastrulation movements in connection with the Snail/E-cadherin pathway.

Weak characteristic information extraction from early fault of wind turbine generator gearboxKeywords wind turbine generator gearbox, B-singular value decomposition, local mean decomposition, weak characteristic information extraction, early fault warning

Given the weak early degradation characteristic information during early fault evolution in gearbox of wind turbine generator, traditional singular value decomposition （SVD）-based denoising may result in loss of useful information. A weak characteristic information extraction based on μ-SVD and local mean decomposition （LMD） is developed to address this problem. The basic principle of the method is as follows： Determine the denoising order based on cumulative contribution rate, perform signal reconstruction, extract and subject the noisy part of signal to LMD and μ-SVD denoising, and obtain denoised signal through superposition. Experimental results show that this method can significantly weaken signal noise, effectively extract the weak characteristic information of early fault, and facilitate the early fault warning and dynamic predictive maintenance.

Identification of the distinguishing features of Crohn’s disease and ischemic colitis using computed tomographic enterography

Background and aims:The differential diagnosis between Crohn’s disease(CD)and ischemic colitis(ISC)is important as their clinical management is different.ISC can easily be misdiagnosed as CD,especially in elderly populations.The distinctive radiographic features of the two disease entities have not been investigated.The aim of this study is to assess the utility of computed tomographic enterography(CTE)in the differential diagnosis between CD and ISC.Methods:Patients with confirmed CD and ISC were identified through an electronic medical record search of the Cleveland Clinic Foundation.Patients who had undergone CTE,with or without concurrent colonoscopy and histopathological specimens,were included in this study.CTE images were blindly re-reviewed by an expert gastrointestinal radiologist.The sensitivities,specificities,accuracies and positive and negative predictive values for each of the CTE findings in differentiating CD from ISC were estimated.Kappa coefficients(j)were calculated tomeasure diagnosis agreement between CTE and the reference standard.Results:A total of 34 eligible patients were included in this study with 17 having CD and 17 having ISC.In differentiating CD from ISC,the presence ofmucosal hyperenhancement and absence of the“target sign”on CTE showed a sensitivity of 100% each for CD,while the two radiographic features yielded a low specificity of 35.3%and 76.5%,respectively.The presence of stricture had a lower sensitivity of 64.7% for the detection of CD but had a high specificity of 100%.In distinguishing CD fromISC,the accuracy of presence ofmucosal hyperenhancement,stricture and absence of target sign were 67.7%,82.4% and 88.2%,respectively.The combination of the presence ofmucosal hyperenhancement and the absence of the target sign achieved an accuracy of 100%for distinguishing CD from ISC.There was a good correlation between CTE and the reference standard for distinguishing CD fromISC(k=0.882).Conclusions:CTE appeared to be clinically useful in distinguishing CD from ISC.

Neural spike train reconstruction from calcium imaging via a signal-shape composition model

Dear Editor,Since calcium imaging can simultaneously record the calcium signals of several hundred neurons, it has been a powerful tool in measuring the functional activity of neural populations. However, calcium imaging is an indirect measurement of neuronal firing activity, and this technique requires reconstructing the AP trains from the corresponding calcium fluorescence signals of the recorded neurons.

Generation ofαGal-enhanced bifunctional tumor vaccine

Hepatocellular carcinoma(HCC)is a common malignant tumor with poor prognosis and high mortality.In this study,we demonstrated a novel vaccine targeting HCC and tumor neovascular endothelial cells by fusing recombinant MHCC97H cells expressing porcine a-1,3-galactose epitopes(a Gal)and endorphin extracellular domains(END)with dendritic cells(DCs)from healthy volunteers.END^(+)/Gal^(+)-MHCC97H/DC fusion cells induced cytotoxic T lymphocytes(CTLs)and secretion of interferon-gamma(IFN-γ).CTLs targeted cells expressing a Gal and END and tumor angiogenesis.The fused cell vaccine can effectively inhibit tumor growth and prolong the survival time of human hepatoma mice,indicating the high clinical potential of this new cell based vaccine.

Averrhoa carambola extractive inhibits breast cancer via regulating CEPT1 and LYPLA1

Liposomes have been widely exploited as a drug delivery system in treating tumors because of their advantage to enhance anti-tumor efficacy and reduce side effects. In this study, the tumor-targeted 2-dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione(DMDD, i.e., Averrhoa carambola extractive) liposomes(HA/TN-DLP) were conducted and assessed. HA/TN-DLP showed controllable drug loading(up to 83%)with high stability. In vitro and in vivo studies showed good cell uptake behavior and high inhibition rate of breast cancer compared to free DMDD. HA/TN-DLP might be the suitable for DMDD due to its better advantages in delivery, penetrability, and targeting-tumor capability. For in vivo mouse model tests,HA/TN-DLP effectively inhibited tumor growth compared to free DMDD. Further analyses indicated that HA/TN-DLP inhibited the glycerophospholipid metabolism pathway by reducing the biosynthesis of phosphatidylcholine and 1-acyl-sn-glycero-3-phosphocholine through regulating the expressions of CEPT1 and LYPLA1, and inhibited tumor cell growth by regulating the PI3K/Akt and NF-κ B signaling pathways. In conclusion, the obviously enhanced antitumor effect further demonstrated that HA/TN-DLP may be a promising tumor-targeting agent.

A recombinant Newcastle disease virus expressing MMP8 promotes oncolytic efficacy

Oncolytic virus is an emerging anti-cancer strategy. However, extracellular matrix(ECM), as a physical barrier, limits virus spread within the tumor. To overcome the obstacle, we constructed a recombinant Newcastle disease virus(NDV) expressing matrix metalloproteinase(MMP8)(NDV-MMP8) using with reverse genetic technology. In vitro, NDV-MMP8 was identified and verified by WB and ELISA. Cell viability was detected by CCK-8 assay. In vivo, we established two liver cancer xenograft models. NDV-MMP8 was injected into the tumor to observe the tumor volume and survival of mice. The changes in extracellular matrix were observed by Masson’s trichrome staining. Virus expression in tumor tissues was detected by immunofluorescence assay. The virus titer in tumor tissues was detected by TCID50. Histopathological changes were detected by hematoxylin and eosin(HE) and terminal deoxynucleotidyl transferase d UTP nick end labeling(TUNEL) staining. Intratumoral administration of NDV-MMP8 can effectively degrade ECM, promote the spread of the virus within the tumor, and reduce tumor growth rate. Therefore, the method of increasing intratumoral virus accumulation by degradation of the ECM to enhance the oncolytic effect has great potential for clinical application.

Histologic patterns of liver injury induced by anti-PD-1 therapy

Background:Nivolumab and pembrolizumab—two monoclonal antibodies that block human programmed cell death-1(PD-1)—have been successfully used to treat patients with multiple advanced malignancies.The histologic patterns of hepatic toxicity induced by anti-PD-1 treatment have not been well studied and the aim of this study was to explore them.Methods:Eight patients with advanced malignancies who were treated with either nivolumab or pembrolizumab were identified from five institutions.These patients had no history of underlying liver disease and a viral hepatitis panel was negative in all patients.Results:Seven of eight patients exhibited mild to moderate gastrointestinal symptoms such as abdominal pain,fatigue,nausea,vomiting,and jaundice after anti-PD-1 treatment.Significant elevations in liver-chemistry tests were detected in all patients.Six cases(6/8)demonstrated an acute lobular hepatitis pattern of histologic injury.The remaining two cases showed different histologic patterns of injury:steatohepatitis with mild cholestasis(1/8)and pure acute cholestatic injury(1/8).No case showed typical features of autoimmune hepatitis.The liver function recovered in all eight cases after cessation of anti-PD-1 agents and with immunosuppressive therapy.Conclusions:Our study suggests that screening patients for abnormal liver-function tests prior to anti-PD-1 therapy as well as periodic monitoring of liver-function tests are necessary to prevent severe liver injury.Rather than causing classical autoimmune hepatitis,PD-1 inhibitors appear to produce an immune-mediated nonspecific acute hepatitis.Drug cessation,without steroid therapy,may therefore be sufficient in some patients.

Overexpression of p53 predicts colorectal neoplasia risk in patients with inflammatory bowel disease and mucosa changes indefinite for dysplasia

Background and aims:We previously demonstrated a significant colorectal neoplasia risk in inflammatory bowel disease(IBD)patients with mucosal changes indefinite for dysplasia(IND)and the potential diagnostic utility of p53 and cytokeratin 7 immunohistochemistry in IBD-associated neoplasia.The primary aim of this exploratory study was to determine the predictive value of the two markers for neoplasia risk in the IBD-IND population.Methods:We identified 44 eligible cases with IBD and IND in colon biopsy from our pathology database.We semi-quantified the expression of p53 and cytokeratin 7 in the colon biopsies by immunohistochemistry and correlated their expression,demographic information,and clinical features with colorectal neoplasia outcome.Results:The mean age of the cohort was 46.6615.1 years,with 25(56.8%)being male.The median follow-up was 101 months(range:6–247)after IND diagnosis.Among these 44 patients,11(25%)progressed to neoplasia(low-grade dysplasia¼6;high-grade dysplasia¼2;cancer 3)at a median follow-up of 66 months(range:19–145).Univariate analysis demonstrated that age and p53 overexpression were associated with progression to neoplasia.Conclusions:Twenty-five percent of patients with IBD and IND developed colorectal dysplasia or cancer.Overexpression of p53 and age are associated with neoplastic progression.