TET2 regulates extranodal NK/T cell lymphoma progression through regulation of DNA methylation.

The biological role of Ten-11 translocation 2 (TET2) and the conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) in the development of extra-nodal natural killer/T-cell lymphoma (ENKTL) remains unclear. The level of 5mC and 5hmC was detected in 112 cases of ENKTL tissue specimens by immunohistochemical (IHC) staining. Subsequently, TET2 knockdown and the overexpression cell models were constructed in ENKTL cell lines. Biochemical analyses were used to assess proliferation, apoptosis, cell cycle and monoclonal formation in cells treated or untreated with L-Ascorbic acid sodium salt (LAASS). Dot-Blots were used to detect levels of genome 5mC and 5hmC. Additionally, the ILLUMINA 850k methylation chip was used to analyze the changes of TET2 regulatory genes. RNA-Seq was used to profile differentially expressed genes regulated by TET2. The global level of 5hmC was significantly decreased, while 5mC was highly expressed in ENKTL tissue. TET2 protein expression was negatively correlated with the ratio of 5mC/5hmC (p < 0.0001). The 5mC/5hmC status were related to the site of disease, clinical stage, PINK score and Ki-67 index, as well as the 5-year OS. TET2 knockdown prolonged the DNA synthesis period, increased the cloning ability of tumor cells, increased the level of 5mC and decreased the level of 5hmC in ENKTL cells. While overexpression of TET2 presented the opposite effect. Furthermore, treatment of ENKTL cells with LAASS significantly induced ENKTL cell apoptosis. These results suggest that TET2 plays an important role in ENKTL development via regulation of 5mC and 5hmC and may serve as a novel therapeutic target for ENKTL.

Smooth endoplasmic reticulum aggregates in oocytes associated with increased risk of neonatal birth defects: A meta-analysis.

INTRODUCTION: Previous studies have indicated the association between smooth endoplasmic reticulum aggregates (SERa+) and poorer medically assisted reproduction outcomes. However, the link between SERa+ and neonatal outcomes remains controversial and open for debate. A comprehensive meta-analysis on the relation between SERa+ and the risk of birth defects is needed. MATERIAL AND METHODS: The literature search was conducted using the following databases: PubMed, Embase, Cochrane Libraries, Web of Science, and Chinese databases including China National Knowledge Infrastructure (CNKI) and Wan Fang from inception until July 2023. Risk ratio (RR) and 95% confidence interval (CI) were calculated by a fixed-effected model, while heterogeneity was assessed by forest plots and I2 statistic. Funnel plot was produced to assess publication bias. This meta-analysis has been registered on PROSPERO (CRD42022313387). RESULTS: The search resulted in 122 studies, 14 of which met the inclusion criteria. The analysis of birth defects revealed a higher risk (RR = 2.17, 95%CI 1.24 to 3.81, p = 0.007) in children derived from SERa+ cycle compared to SERa- cycles (711 vs. 4633). Meanwhile, in a subgroup analysis, the risk of birth defects was significantly increased in the SERa+ oocytes group as compared with the sibling SERa- oocytes group (RR = 3.53, 95%CI 1.21 to 10.24, p = 0.02). CONCLUSIONS: To conclude, our analysis indicated that SERa+ cycles/oocytes may have a potential risk of increased additional major birth defects comparing with SERa- cycles/oocytes. This conclusion may provide evidence-based support for clinicians in IVF clinical guidance and embryologists in prudent embryo selection strategy.

An overview of CFTR mutation profiles and assisted reproductive technology outcomes in Chinese patients with congenital obstructive azoospermia.

PURPOSE: The cystic fibrosis transmembrane conductance regulator (CFTR) is the most common causative gene attributed to congenital obstructive azoospermia (OA). The aim of this study was to conduct an epidemiological survey of congenital OA patients, to screen for CFTR mutations, and to follow their pregnancy outcomes in assisted reproductive technology (ART). METHODS: This cohort study enrolled congenital OA patients undergoing ART and whole-exome sequencing from January 2018 to September 2023. Semen parameters, sex hormones, and seminal plasma biochemistry were evaluated. CFTR mutations identified in OA patients were analyzed. In addition, the laboratory outcomes, clinical outcomes, and neonatal outcomes were compared between OA patients carrying two CFTR mutations and the others after surgical sperm extraction-intracytoplasmic sperm injection (ICSI) treatment. RESULTS: A total of 76 patients with congenital OA were enrolled. CFTR mutations were identified in 35 (46.1%) congenital OA patients. A total of 60 CFTR mutation sites of 27 types were identified, and 10 of them were novel. The average frequency was 1.71 (60/35) per person. The most common mutation was c.1210-11T > G (25%, 15/60). After ICSI treatment, there were no statistically significant differences in laboratory outcomes, clinical outcomes, and neonatal outcomes between OA patients carrying two CFTR mutations (n = 25) and other OA patients (n = 51). CONCLUSION: Apart from the IVS9-5T mutation, the genetic mutation pattern of CFTR in Chinese OA patients is heterogeneous, which is significantly different from that of Caucasians. Although carrying two CFTR mutations or not had no effect on the pregnancy outcomes in OA patients after ICSI, genetic counseling is still recommended for such patients.

Study on the Tip Leakage Loss Mechanism of a Compressor Cascade Using the Enhanced Delay Detached Eddy Simulation Method.

The leakage flow has a significant impact on the aerodynamic losses and efficiency of the compressor. This paper investigates the loss mechanism in the tip region based on a high-load cantilevered stator cascade. Firstly, a high-fidelity flow field structure was obtained based on the Enhanced Delay Detached Eddy Simulation (EDDES) method. Subsequently, the Liutex method was employed to study the vortex structures in the tip region. The results indicate the presence of a tip leakage vortex (TLV), passage vortex (PV), and induced vortex (IV) in the tip region. At i=4°,8°, the induced vortex interacts with the PV and low-energy fluid, forming a "three-shape" mixed vortex. Finally, a qualitative and quantitative analysis of the loss sources in the tip flow field was conducted based on the entropy generation rate, and the impact of the incidence on the losses was explored. The loss sources in the tip flow field included endwall loss, blade profile loss, wake loss, and secondary flow loss. At i=0°, the loss primarily originated from the endwall and blade profile, accounting for 40% and 39%, respectively. As the incidence increased, the absolute value of losses increased, and the proportion of loss caused by secondary flow significantly increased. At i=8°, the proportion of secondary flow loss reached 47%, indicating the most significant impact.

Large-scale exploration of nitrogen utilization efficiency in Asia region for rice crop: Variation patterns and determinants.

Improving rice nitrogen utilization efficiency (NUtE) is imperative to maximizing future food productivity while minimizing environmental threats, yet knowledge of its variation and the underlying regulatory factors is still lacking. Here, we integrated a dataset with 21,571 data compiled by available data from peer-reviewed literature and a large-scale field survey to address this knowledge gap. The overall results revealed great variations in rice NUtE, which were mainly associated with human activities, climate conditions, and rice variety. Specifically, N supply rate, temperature, and precipitation were the foremost determinants of rice NUtE, and NUtE responses to climatic change differed among rice varieties. Further prediction highlighted the improved rice NUtE with the increasing latitude or longitude. The indica and hybrid rice exhibited higher NUtE in low latitude regions compared to japonica and inbred rice, respectively. Collectively, our results evaluated the primary drivers of rice NUtE variations and predicted the geographic responses of NUtE in different varieties. Linking the global variations in rice NUtE with environmental factors and geographic adaptability provides valuable agronomic and ecological insights into the regulation of rice NUtE.

Extranodal natural killer/T-cell lymphoma with hepatosplenic involvement: a retrospective study of a consecutive 14-year case series.

Extranodal natural killer/T-cell lymphoma (ENKTL) with hepatosplenic involvement is rare, accounting for approximately 0.2% of ENKTL cases. The clinicopathologic features of ENKTL with hepatosplenic involvement are still poorly understood. Seven cases of ENKTL with hepatosplenic involvement were investigated retrospectively by clinical features, pathology, immunophenotype, genotype, Epstein-Barr virus (EBV) status, and survival analysis. The median age was 36 years; three patients (3/7) had a history of primary nasal ENKTL. Six cases (6/7) presented liver or spleen structures that were replaced by neoplasms, and the neoplastic cells displayed diffuse infiltration; one case (1/7) displayed neoplastic cells scattered in hepatic sinuses and portal areas. The cellular morphology and immunohistochemical features were similar to those of ENKTL involving other sites. Follow-up data were available in five of the seven patients. All five patients received first-line chemotherapy based on L-asparaginase. Three patients died, and two were still alive by the last follow-up. The median overall survival (OS) was 21 months. ENKTL with hepatosplenic involvement is rare, regardless of whether it is initial or secondary. There are two histopathologic patterns of ENKTL with hepatosplenic involvement, and L-asparaginase-based chemotherapy combined with AHSCT might yield good efficacy. Morphological features of ENKTL in the spleen and liver A The architecture of the spleen was affected, and dense infiltration of the neoplastic cells was observed in the left part; B Focal infiltration of the neoplastic cells was located in the red pulp; C Dense infiltration of the neoplastic cells in the liver, accompanied by fatty change of hepatocytes and congestion; D More neoplastic cells accumulated in sinusoidal region.

Design method of freeform off-axis three-mirror reflective imaging systems.

In this paper, a novel, to the best of our knowledge, method is proposed to design a freeform off-axis three-mirror reflective imaging system. A special algorithm is demonstrated to calculate the data points on the unknown freeform surface using the rays from the pupil of the center field. Then the three-dimensional shape of the freeform surface is solved by these characteristic points, which serves as a good starting point for further optimization. The benefit of this design method is demonstrated by designing a freeform off-axis three mirror imaging system with high performance. The final system operates at F/2 with an entrance pupil diameter of 400 mm and a field of view of 2.4∘×2.4∘. The modulation transfer function (MTF) value of the system reaches 0.6 at 100 lp/mm or higher at all fields of view.

Genetic dissection of heterotic loci associated with plant weight by Graded pool-seq in heading Chinese cabbage (Brassica rapa).

MAIN CONCLUSION: Four heterotic QTL and a heterozygous segment for plant weight were identified by Graded Pool-Seq, QTL-seq and traditional genetic linkage analysis in heading Chinese cabbage. Heading Chinese cabbage (Brassica rapa L. spp. pekinensis) is a cross-pollinated leafy vegetable with significant heterosis. The use of heterosis is important for breeding high-yield Chinese cabbage hybrids. However, the formation and mechanism of heterosis have not been studied. We dissected the molecular mechanism of heterosis of yield-related traits in Chinese cabbage. An F1 hybrid with high-parent heterosis of yield-related traits was selected and self-pollinated to generate segregating F2 populations. QTL-seq, Graded Pool-seq (GPS), and traditional genetic linkage analysis were used to identify four heterotic quantitative trait loci (QTL) for plant weight: qPW1.1, qPW5.1, qPW7.1, and qPW8.1. Traditional genetic linkage analysis over two years showed that qPW8.1, located in marker A08_S45 (18,172,719) and A08_S85 (18,196,752), was mapped to a 23.5 kb genomic region. QTL qPW8.1 explained 8.6% and 23.6% of the phenotypic variation in plant weight and the total numbers of head leaves, respectively, and contained a heterozygous segment that might control the heterosis of plant weight. The qPW1.1 made an 11.7% phenotypic contribution to plant weight. The qPW7.1 was sensitive to environmental influence and explained 10.7% of the phenotypic variance. QTL qPW5.1 had a significant signal and was located in a genetic region near the centromere showing high heterozygosity. The "pseudo-overdominance" and "synergistic allelic" effects from parent line "XJD4" appear to play an important role in heterosis for plant weight in Chinese cabbage. These results provide a basis for an improved understanding of the molecular mechanism of yield-related traits and their heterosis.

Prognostic value and computer image analysis of p53 in mantle cell lymphoma.

P53 prognostic cut-off values differ between studies of mantle cell lymphoma (MCL), and its immunohistochemistry (IHC) interpretation is still based on semiquantitative estimation, which might be inaccurate. This study aimed to investigate the optimal cut-off value for p53 in predicting prognosis of patients with MCL and the possible use of computer image analysis to identify the positive rate of p53. We calculated p53 positive rate using QuPath software and compared it with the data obtained by manual counting and semiquantitative estimation. Survival curves were generated by using the Youden index and the Kaplan-Meier method. The chi-squared (χ2) test was used to compare MIPI, Ann Arbor stage, and cell morphology with p53. Spearman rank correlation test and Bland-Altman analysis were used to compare manual counting, computer image analysis and semiquantitative estimation, as well as the consistency between different observers. The optimal cut-off value of p53 for predicting prognosis was 20% in MCL patients. Patients with p53 ≥ 20% had a significantly worse overall survival (OS) than those with p53 < 20% (P < 0.0001). MCL patients with MIPI intermediate to high risk, Ann Arbor stage III-IV, and blastoid/pleomorphic variant cell morphology had more p53 ≥ 20%. There was a strong correlation between computer image analysis and manual counting of p53 from the same areas in MCL tissues (Spearman's rho = 0.966, P < 0.0001). The results of computer analysis are completely consistent between observers, and computer image analysis of Ki-67 can predict the prognosis of MCL patients. MCL patients with p53 ≥ 20% had a shorter OS and a tendency for MIPI intermediate to high risk, Ann Arbor stage III-IV, and blastoid/pleomorphic variant. Computer image analysis could determine the actual positive rate of p53 and Ki-67 and is a more attractive alternative than semiquantitative estimation in MCL.

Novel tumour-infiltrating lymphocyte-related risk stratification based by flow cytometry for patients with de novo angioimmunoblastic T cell lymphoma.

Tumour-infiltrating lymphocytes (TILs) account for a large proportion of tumour microenvironment (TME) in angioimmunoblastic T cell lymphoma (AITL), and at present the significance of TIL in TME of AITL remains unclear. Overall, 50 de novo AITL patients undergoing lymph node flow cytometry from 2014 to 2019 were retrospectively analysed to assess the relationship between TILs and AITL prognosis. We found that high TIL-Bs (≥ 42.4%, p = 0.004) and high CD4:CD8 (≥ 0.85, p = 0.024) were independent favourable prognostic factors for de novo AITL in univariate or multivariate analyses. New TIL-related risk stratification was established based on TIL-Bs and CD4:CD8 factors. Patients in the low-risk group (TIL-Bs ≥ 42.4% and CD4:CD8 ≥ 0.85) had significantly better overall survival than the high-risk (TIL-Bs < 42.4% and CD4:CD8 < 0.85) (p < 0.001) or intermediate-risk group (TIL-Bs ≥ 42.4% and CD4:CD8 < 0.85 or TIL-Bs < 42.4% and CD4:CD8 ≥ 0.85) (p = 0.011). To our knowledge, our cohort is the largest one focusing on the TILs in de novo cases of AITL by analysing lymph node samples using flow cytometry, which is the first time to comprehensively consider humoral immunity and cellular immunity influence on AITL. Our new risk stratification was valuable and useful in evaluating prognosis of AITL and guiding immunotherapy strategies.

Dihydroartemisinin alleviates high glucose-induced vascular smooth muscle cells proliferation and inflammation by depressing the miR-376b-3p/KLF15 pathway.

Inflammation and the proliferation of vascular smooth muscle cells (VSMCs) are seen to play critical roles in the development of vascular complications induced by diabetes and hyperglycemia. Dihydroartemisinin (DHA) has been identified as a semi-synthetic derivative of artemisinin that exhibits broad protective effects. However, the effect of DHA on high glucose (HG)-induced inflammation and proliferation of VSMCs remains unknown. Therefore, this study aims to show that DHA significantly inhibited the proliferation of VSMCs and that expression of the inflammatory cytokines IL-1ß and TNF-α was induced by HG in a dose-dependent manner. Additionally, we were able to determine that KLF15 played a critical role in HG-induced VSMC proliferation and inflammation, confirming its protective effects observed after DHA treatment in the HG-induced inflammatory response of VSMCs. DHA was observed to directly depress the HG-induced expression of miR-376b-3p, which targeted the 3'-UTR of KLF15 and inhibited its expression. These results suggested that DHA plays a protective role in HG-induced VSMC proliferation and associated inflammation by inhibiting the miR-376b-3p/KLF15 axis. Our findings provide new evidence of the mechanisms of DHA and its critical role in treating the pathogenesis of diabetic vascular complications.

Anatomically induced changes in rice leaf mesophyll conductance explain the variation in photosynthetic nitrogen use efficiency under contrasting nitrogen supply.

BACKGROUND: The ratio of CO2 mesophyll conductance (gm) to Ribulose-1, 5-bisphosphate carboxylase/oxygenase (Rubisco) content has been suggested to positively affect photosynthetic nitrogen use efficiency (PNUE). The anatomical basis of gm has been quantified, but information on the relationship between cell-level anatomies and PNUE is less advanced. Here, hydroponic experiments were conducted in rice plants supplied with ammonium (NH4+) and nitrate (NO3-) under three N levels (low, 0.71 mM; intermediate, 2.86 mM; high, 7.14 mM) to investigate the gas exchange parameters, leaf anatomical structure and PNUE. RESULTS: The results showed a lower PNUE in plants supplied with high nitrogen and NH4+, which was positively correlated with the gm/Rubisco ratio. A one-dimensional within-leaf model revealed that the resistance to CO2 diffusion in the liquid phase (rliq) dominated the overall mesophyll resistance (rm), in which CO2 transfer resistance in the cell wall, cytoplasm and stroma were significantly affected by nitrogen supply. The chloroplast surface area exposed to intercellular space (Sc) per Rubisco rather than the gm/Sc ratio was positively correlated with PNUE and was thus considered a key component influencing PNUE. CONCLUSION: In conclusion, our study emphasized that Sc was the most important anatomical trait in coordinating gm and PNUE with contrasting N supply.

Soil fungal assemblage complexity is dependent on soil fertility and dominated by deterministic processes.

In the processes controlling ecosystem fertility, fungi are increasingly acknowledged as key drivers. However, our understanding of the rules behind fungal community assembly regarding the effect of soil fertility level remains limited. Using soil samples from typical tea plantations spanning c. 2167 km north-east to south-west across China, we investigated the assemblage complexity and assembly processes of 140 fungal communities along a soil fertility gradient. The community dissimilarities of total fungi and fungal functional guilds increased with increasing soil fertility index dissimilarity. The symbiotrophs were more sensitive to variations in soil fertility compared with pathotrophs and saprotrophs. Fungal networks were larger and showed higher connectivity as well as greater potential for inter-module connection in more fertile soils. Environmental factors had a slightly greater influence on fungal community composition than spatial factors. Species abundance fitted the Zipf-Mandelbrot distribution (niche-based mechanisms), which provided evidence for deterministic-based processes. Overall, the soil fungal communities in tea plantations responded in a deterministic manner to soil fertility, with high fertility correlated with complex fungal community assemblages. This study provides new insights that might contribute to predictions of fungal community complexity.

Characterization of Response Frequency for the Pressure-Sensitive Paint Based on Fluorine-Containing Polymer Matrixes Using Oscillating Sound Wave Technique.

Five kinds of new homo-polymer and copolymers of methacrylate containing a fluorine ester group were synthesized and used for the binder of pressure-sensitive paint (PSP)to ensure the good compatibility between luminophore (Pt(II) meso-tetra (pentafluorophenyl) porphine (PtTFPP)) and polymer binder. In the work, we were concerned with how the structure of thesepolymers containing fluorine, especially the various ester group structure, affects the response frequency of PSP using oscillating sound wave technique. The results showed that the pressure sensitivities (Sp) of these PSP samples containing different polymers, exhibit some difference. The length of ester chain on the methacrylatepolymer affects the response frequency of PSP sensor layer composed of the polymer. The longer the chain length of the ester group, the higher the response frequency of the PSP sensor layer quenching by oxygen.

Generalized crystal-storing histiocytosis with diffuse large B-cell lymphoma and monoclonal gammopathy in a Chinese elderly woman: a case report.

BACKGROUND: Crystal-storing histiocytosis (CSH) is a rare lesion characterized by sheets of crystal-laden non-neoplastic histiocytes. CSH shows a prominent association with lymphoproliferative disorders that express monoclonal immunoglobulins, mainly multiple myeloma (MM), lymphoplasmacytic lymphoma (LPL) and monoclonal gammopathy of undetermined significance (MGUS). However, no aggressive B cell lymphoma has been reported to be associated with CSH. CASE PRESENTATION: A 74-year-old Chinese woman presented with multiple subcutaneous masses, abdominal pain, and fever. An IgM kappa type of monoclonal gammopathy (MG) was noted by immunofixation performed on the patient's serum. Computed tomographic (CT) scan revealed subcutaneous masses on the left upper arm and at the waist and multiple low-density lesions in the spleen. Microscopically, sections of subcutaneous masses revealed sheets of large polygonal and spindle cells with abundant eosinophilic cytoplasm, round to ovoid eccentric nuclei, reticulate chromatin, and median nucleoli. Massive needle-shaped crystals were confined to the cytoplasm. Immunohistochemically, these crystal-containing cells were positive for CD68/PGM1, CD163, IgM, and Igκ. Meanwhile, the splenic tumour was diagnosed as diffuse large B-cell lymphoma (DLBCL), non-germinal-centre B (non-GCB) subtype (Hans algorithm). Immunohistochemistry for IgM was positive in the cytoplasm of some neoplastic cells. Immunoglobulin heavy chain (IgH) gene rearrangement was detected by PCR analysis of the subcutaneous mass and the splenic tumour. CONCLUSION: To the best of our knowledge, this is the first case of generalized CSH with DLBCL and MG. Although the rarity of CSH and separate locations of CSH and lymphoma led to a diagnostic dilemma, the presence of MG was a clue to appreciate the relation between CSH and DLBCL. This case stressed a full investigation into the underlying lymphoproliferative disorder for integrated diagnosis and correct treatments.

Novel risk stratification of de novo diffuse large B cell lymphoma based on tumour-infiltrating T lymphocytes evaluated by flow cytometry.

The prognostic value of tumour-infiltrating T lymphocytes (TIL-Ts) has been demonstrated in many solid tumours but remained unclear in diffuse large B cell lymphoma (DLBCL). We conducted a retrospective cohort study reviewing the TIL-Ts proportion and CD4:CD8 of 66 de novo DLBCL by flow cytometry to construct a risk stratification based on TIL-Ts-related prognostic factors. In univariate analysis, low TIL-Ts (< 14%) was significantly related to shorter survival (HR = 2.58, 95% CI 1.11-5.99, p = 0.028). In multivariate analysis, low TIL-Ts (HR = 6.48, 95% CI 2.16-19.46, p = 0.001) and high CD4:CD8 (> 1.2) (HR = 4.22, 95% CI 1.43-12.35, p = 0.009) were independent risk factors. For the risk stratification, three groups were defined based on TIL-Ts-related risk factors: low-risk group (high TIL-Ts and low CD4:CD8), intermediate risk group (low TIL-Ts, low CD4:CD8 or high TIL-Ts, high CD4:CD8) and high-risk group (low TIL-Ts and high CD4:CD8). The patients in high-risk group have significantly shorter survival than that in intermediate risk group (p = 0.025) and low-risk group (p = 0.002). This new risk stratification which is independent of performance status and age of the patients could hint the prognosis and may guide treatment of DLBCL.

Epstein-Barr virus positive peripheral T cell lymphoma with novel variants in STAT5B of a pediatric patient: a case report.

BACKGROUND: Epstein-Barr virus positive peripheral T cell lymphoma (EBV + PTCL) is a rare type of lymphoproliferative disorder which is always present in late adulthood. However, pediatric EBV + PTCL is extremely rare and always present with lymphadenopathy. Additionally, gene detection was not performed in all of these pediatric patients. CASE PRESENTATION: We report an EBV + PTCL in a 9-year-old child with initial symptom of subcutaneous masses without lymph node involvement. Histologically, the neoplastic cells were centroblastoid with round or oval nuclei, slightly condensed chromatin and median eosinophilic inconspicuous nucleoli. Immunohistochemically, all neoplastic cells were positive for CD8, GranzymeB and TIA-1. Two novel variants (S420Y and E623K) were detected in STAT5B. CONCLUSION: To the best of our knowledge, this is the first case of EBV + PTCL with STAT5B variants of a pediatric patient presented as extranodal lesions.

An update on the management of pancreatic neuroendocrine tumors.

Pancreatic neuroendocrine tumors (PNETs) are a rare and heterogeneous group of neoplasia and differ in their clinical presentation, behavior, and prognosis based on both histological features and cancer stage at the time of diagnosis. Although small-sized tumors can be surgically resected, locally advanced and metastatic tumors confer a poor prognosis. In addition, only limited treatment options are available to the latter group of patients with PNETs, such as hormonal analogs, cytotoxic agents, and targeted therapy. In selected patients, liver-directed therapies are also used. As expected, clinicians taking care of these patients are challenged to develop an effective and comprehensive treatment strategy for their patients amid a wide variety of treatment modalities. Targeted therapy for PNETs is limited to sunitinib and everolimus. Presently, a number of clinical studies are ongoing to assess the efficacy of newer targeted agents alone and in combination with previous agents for the treatment of advanced PNETs. The authors reviewed the current treatment and also discussed the emerging agents and emphasized the need to identify biomarkers.

Piezoresistivity of resin-impregnated carbon nanotube film at high temperatures.

This paper presents the development of a continuous carbon nanotube (CNT) composite film sensor with a strain detecting range of 0%-2% for structural composites. The strain-dependent resistance responses of continuous CNT film and its resin-impregnated composite films were investigated at temperatures as high as 200 °C. The results manifest that impregnation with resin leads to a much larger gauge factor than pristine film. Both the pristine and composite films show an increase in resistivity with increasing temperature. For different composite films, the ordering of gauge factors is consistent with that of the matrix moduli. This indicates that a resin matrix with higher modulus and strong interactions between CNTs/CNT bundles and the resin matrix are beneficial for enhancing the piezoresistive effect. The CNT/PAA composite film has a gauge factor of 4.3 at 150 °C, an order of magnitude higher than the metal foil sensor. Therefore, the CNT composite films have great potential for simultaneous application for reinforcement and as strain sensor to realise a multifunctional composite.

Improved force prediction model for grinding Zerodur based on the comprehensive material removal mechanism.

There have been few investigations dealing with the force model on grinding brittle materials. However, the dynamic material removal mechanisms have not yet been sufficiently explicated through the grain-workpiece interaction statuses while considering the brittle material characteristics. This paper proposes an improved grinding force model for Zerodur, which contains ductile removal force, brittle removal force, and frictional force, corresponding to the ductile and brittle material removal phases, as well as the friction process, respectively. The critical uncut chip thickness agc of brittle-ductile transition and the maximum uncut chip thickness agmax of a single abrasive grain are calculated to identify the specified material removal mode, while the comparative result between agmax and agc can be applied to determine the selection of effective grinding force components. Subsequently, indentation fracture tests are carried out to acquire accurate material mechanical properties of Zerodur in establishing the brittle removal force model. Then, the experiments were conducted to derive the coefficients in the grinding force prediction model. Simulated through this model, correlations between the grinding force and grinding parameters can be predicted. Finally, three groups of grinding experiments are carried out to validate the mathematical grinding force model. The experimental results indicate that the improved model is capable of predicting the realistic grinding force accurately with the relative mean errors of 6.04% to the normal grinding force and 7.22% to the tangential grinding force, respectively.