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BACKGROUND: We aimed to investigate perineal nerve block versus periprostatic block in pain control for men undergoing a transperineal prostate biopsy. METHODS: In this prospective, randomised, blinded and parallel-group trial, men in six Chinese hospitals with suspected prostate cancer were randomly assigned (1:1) at the point of local anaesthesia to receive a perineal nerve block or periprostatic block and followed by a transperineal prostate biopsy. Centres used their usual biopsy procedure. Operators who performed anaesthesia were trained in both techniques before the trial and were masked to the randomised allocation until the time of anaesthesia and were not involved in the subsequent biopsy procedure and any assessment or analysis. Other investigators and the patients were masked until trial completion. The primary outcome was the level of the worst pain experienced during the prostate biopsy procedure. Secondary outcomes included pain (post-biopsy at 1, 6 and 24 h), changes in blood pressure, heart rate and breathing rate during the biopsy procedure, external manifestations of pain during biopsy, anaesthesia satisfaction, the detection rate of PCa and clinically significant PCa. This trial is registered on ClinicalTrials.gov, NCT04501055. FINDINGS: Between August 13, 2020, and July 20, 2022, 192 men were randomly assigned to perineal nerve block or periprostatic block, 96 per study group. Perineal nerve block was superior for the relief of pain during the biopsy procedure (mean 2.80 for perineal nerve block and 3.98 for periprostatic block; adjusted difference in means −1.17, P

Changes in soil CO

Background: The prognostic risk of non-metastatic clear cell renal cell carcinoma (ccRCC) with venous tumor thrombus (VTT) is variable among individual patients following radical nephrectomy and thrombectomy. However, the prognostic potential of multiple pathological features of VTT are unexploited, and risk stratification models specific for these patients are lacking.Patients and methods: This retrospective, nationwide cohort comprised 1263 non-metastatic ccRCC patients with VTT from multicentre, including Training (n=664), China-validation (n=517) and Poland-Validation cohorts (n=82). In addition to the collection of traditional clinicopathologic features, the pathologic characteristics of VTT were centrally reviewed. Independent predictors from multivariable Cox regression analysis were developed into a prognostic model. Harrell's concordance index (c-index), area under the receiver operating characteristic curve (AUC) and decision curve analysis were used to evaluate the association of the variables and prognostic models with overall survival (OS) and disease-free survival (DFS).Results: Using a multi-cohort of 1263 patients, we identified that VTT grading represents an unheeded and powerful independent prognostic factor of adverse outcomes across all cohorts in multivariate analysis for OS and DFS (P < .001; P < .001; P = 0.014 in Training, China-Validation, and Poland-Validation cohorts, respectively). Moreover, VTT grading showed superiority in predicting survival risk compared with the PT grading and other indicators. A risk positioning model, named the TT-GPS score, was constructed based on four independent predictors: VTT height, VTT Grading, Perinephric fat invasion, and Sarcomatoid differentiation in primary tumor. The TT-GPS score displayed better discriminatory ability than available models in risk assessment (OS, c-index: 0.736 and 0.746, AUC: 0.828 and 0.815; DFS, c-index: 0.705 and 0.710, AUC: 0.797 and 0.787 in Training and China-Validation cohorts, respectively). Poland-Validation cohort validated the superiority of the TT-GPS score (OS, c-index: 0.840, AUC: 0.874). Conclusions: VTT grading displayed superior accuracy in prediction of survival risk. By incorporating VTT grading, the TT-GPS score is a powerful predictor of adverse outcomes in non-metastatic ccRCC patients with VTT.

As an elemental carbon (C) and nitrogen (N) pool in the world, peatlands are very sensitive to environmental changes. Under global warming, the increase in available N affects the dynamic changes of plant community structure and nutrients in a permafrost peatland. This study was based on a long-term in situ N addition experiment that had been conducted for 9 years. It utilized the peatland in the permafrost area of Great Hing'an Mountain as the research object to analyze the effects of N addition on the growth characteristics, community structure, and nutrient dynamics of peatland plants. The N inputs were N1: 6 g N m

Background Small cell lung cancer (SCLC) is a highly aggressive lung malignancy which is characteristic of rapid tumor proliferation, metastasis as well as paraneoplastic neurological syndromes (PNS). Recent studies have shown that neuro-oncological ventral antigen-1 (NOVA1) plays a crucial role in the progression of various tumors. However, its effect on SCLC is still exclusive. This study was aimed to explore NOVA1 expression in tumor tissues of SCLC patients as well as its correlation with clinicopathological characteristics and cancer-specific overall survivals. Methods In this study, the patients pathologically diagnosed with new primary SCLC were enrolled. Firstly, we compared NOVA1 expression in SCLC tissues and adjacent normal tissues by immunohistochemistry. We further investigated the association of NOVA1 expression with clinicopathological markers (especially the categories of PNS) and survival time in SCLC patients. Results Our finding exhibited that NOVA1 was remarkably expressed in SCLC tumorous tissues compared with adjacent normal lung tissues (P

Background To investigate the expression of neuro-oncological ventral antigen-1 (Nova1) in small-cell lung cancer (SCLC) and its value in clinical pathological diagnosis of SCLCs. Methods Nova1 expression in the SCLC cell line H446, lung adenocarcinoma cell line A549, squamous cell carcinoma (SCC) cell line H226 and bronchial epithelial cell line BEAS-2B were examined by RT-PCR. It’s expression in paraffin specimens of 100 SCLC cases, 15 specimens of lung adenocarcinoma cases and 15 specimens of lung SCC cases, as well as adjacent normal tissue was determined by immunohistochemistry. The positive rate of Nova1 in SCLC tissue was compared with those of traditional neuroendocrine markers CD56, Syn and CgA. Results Nova1 expression in SCLC cell line H446 was significantly higher than that of bronchial epithelial cell line BEAS-2B and lung adenocarcinoma cell line A549 and SCC cell line H226. The positive rate of Nova1 in SCLC tissue was similar to that of CD56 but higher than those of Syn and CgA. Nova1 was neither expressed in the cancer tissue nor in the adjacent normal tissue of the 15 cases of SCC and the 15 cases of adenocarcinoma. In all six cases of combined SCLC, Nova1 was expressed in the SCLC component, whereas markers of SCC or adenocarcinoma were absent. Conclusions Nova1 can be used as a novel neuroendocrine marker for pathological diagnosis of SCLC in clinical practice with high sensitivity and specificity, in addition to its role as an independent prognostic marker of overall survival and tumour recurrence, as suggested by previous studies.

Background: Despite advances in treatment strategies, the prognosis in early-stage patients with lymph node metastasis (LNM) remains poor, and the 5-year overall survival is ~30%. Therefore, in this study, we aimed to explore the LNM-related long noncoding RNAs (lncRNAs) for the prognosis of cervical cancer patients. We obtained LNM-relevant mRNA and lncRNA expression profiles, copy number variant (CNV), and clinical follow-up data of patients with early-stage cervical cancer from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases.Results: Patients in the training set were divided into a high-risk score group with shorter overall survival (OS) or a low-risk score group with longer OS (p < 0.001); similar results were also determined for the validation set (p < 0.001). In addition, the CNV including chromosome arms 2q, 11q and 18q deletion, 11, 19q and 17q amplification were the most common forms in the high-risk score group. PF4708671 and GW4417556 might be sensitive drugs in chemotherapy, and the programmed death-ligand 1 expression of the low-risk score group was higher than that of the high-risk score group.Conclusions: The prognostic model based on LNM-relevant lncRNAs could help determining the immune status of cervical cancer patients at an early stage; this is conducive to accurate clinical diagnosis and individual treatment.

Immunogenicity has been a major concern in the safety evaluation of therapeutic proteins. The assessment of the unwanted immunogenicity of the therapeutic proteins performed in animals prior to clinical trials has been a regulatory requirement. In preclinical studies of therapeutic proteins, cynomolgus monkeys are usually the most relevant animal species. ZV0203, a recombinant humanized anti-human epidermal growth factor receptor 2 monoclonal antibody covalently bound to a cytotoxic drug (Duo-5), possesses a novel format of antibody drug conjugates. In this study, we reported the development, validation, and application of a bridging enzyme-linked immunosorbent assay for the detection of antibodies against ZV0203 in cynomolgus monkey serum. Drug interference at low positive control (18.0 ng/mL) and high positive control (130 ng/mL) of anti-ZV0203 antibodies was not observed when ZV0203 concentration is below 1.74 μg/mL and 1.49 μg/mL, respectively. In addition, no interference was found from mouse IgG1, but interference was observed with human IgG1. No effect of hemolysis was found on the analysis results of the testing samples present in 100% pooled rabbit serum containing 2% (V/V) erythrocyte hemolysates. Besides, spiked anti-ZV0203 antibody in rabbit serum was stable after 5 freeze/thaw cycles. The results showed that the method is suitable for the detection of anti-ZV0203 antibodies in cynomolgus monkey serum. The assay was also successfully applied in the repeated dose study of ZV0203.

Little is known about the risk of diabetes due to higher glycemic variability and the underlying mechanisms. We aimed to examine the association of visit-to-visit variability (VVV) in fasting plasma glucose (FPG) with incident diabetes in Chinese adults and whether the association was mediated by changes in insulin resistance (IR).We included 1856 community residents without a history of diabetes and having attended 3 examinations in 2008, 2009, and 2013 respectively. The SD, the average successive variability (ASV), the coefficient of variation (CV), and the variability independent of the mean (VIM) of three recorded FPG measurements were calculated for each participant, and SD, ASV, CV, and VIM were used as a measure of VVV in FPG. Incident diabetes was defined according to the 1999 World Health Organization criteria. IR was evaluated using the homeostatic model assessment (HOMA).A total of 153 (8.2%) participants developed incident diabetes at the third visit. Compared with the lowest tertile (0-5.83 mg/dl) of FPG-SD, the highest tertile (9.55-74.17 mg/dl) was associated with a 148% increased risk of diabetes (odds ratio [OR], 2.48; 95% confidence interval [CI], 1.36-4.49), after adjustment for covariates including mean FPG at 3 visits. Mediation analyses suggested that changes in IR (ΔHOMA-IR) might mediate 17.3% of the association between increased FPG-SD and elevated diabetes risk. Similar results were found for FPG-CV, FPG-ASV, and FPG-VIM.The VVV in FPG was significantly associated with risks of diabetes in Chinese adults, which was partially mediated by changes in IR.背景: 由于较高的血糖变异性和潜在机制，人们对糖尿病的风险知之甚少。我们旨在研究中国成年人空腹血糖 (FPG) 的就诊间变异 (VVV) 与糖尿病发病的关系，以及这种关联是否由胰岛素抵抗 (IR)介导。 方法: 我们纳入了1856名无糖尿病病史的社区居民，分别于2008年, 2009年和2013年参加了3次检查。为每个参与者计算了3次FPG测量值的标准差 (SD), 平均连续变异性 (ASV), 变异系数 (CV) 和与平均值无关的变异性 (VIM) 。SD, ASV, CV和 VIM 被用作 FPG 中 VVV 的量度。根据 1999 年世界卫生组织标准定义糖尿病。使用稳态模型评估 (HOMA) 评估 IR。 结果: 共有 153 名 (8.2%) 参与者在第 3 次就诊时出现糖尿病。校正包括 3 次就诊时的平均 FPG在内的协变量后，与 FPG-SD 最低三分位数 (0 - 5.83 mg/dL) 相比，最高三分位数 (9.55-74.17 mg/dL) 糖尿病风险增加 148% (OR = 2.48, 95% CI 1.36-4.49)。中介分析表明，IR的变化(ΔHOMA-IR)可能介导 FPG-SD 增加与糖尿病风险升高之间 17.3% 的关联。对于 FPG-CV , FPG-ASV 和 FPG-VIM 也发现了类似的结果。 结论: FPG 中的 VVV 与中国成年人患糖尿病的风险显着相关，这部分是由 IR 的变化介导的。.

Pancreatic adenocarcinoma is one of the most lethal diseases with a 5-year survival rate of about 8%. ASXL2 is an epigenetic regulator associated with various tumors including colorectal cancer, breast cancer, and myeloid leukemia. However, the role of ASXL2 in pancreatic cancer remains unclear. This is the first research focusing on the prognostic value of ASXL2 in pancreatic cancer. In this research, we aimed to explore the correlation between ASXL2 and the prognosis, as well as other features in PAAD. We obtained gene expression profiles of PAAD and normal tissues from TCGA, GEO, and Xena databases. TIMER and CIBERSORT algorithms were employed to investigate the effect of ASXL2 on tumor microenvironment. GSEA along with GO and KEGG enrichment analyses were conducted to uncover the biological functions of ASXL2. The response to various chemotherapeutic drugs was estimated by algorithms in R package “pRRophetic”, while the sensitivity to immunotherapy was quantified by TIDE score. We found that ASXL2 was upregulated in the PAAD samples and elevated expression of ASXL2 was linked to poor overall survival. ASXL2 DNA methylation contributed to ASXL2 expression. Functional annotation indicated that ASXL2 was mainly involved in inflammatory response and epithelial mesenchymal transition. Patients with high ASXL2 expression were more likely to benefit from immune checkpoint blockade, gemcitabine, and mitomycin-C. Finally, external datasets and biospecimens were used and the results further validated the aberrant expression of ASXL2 in PAAD samples. In summary, our results highlight that ASXL2 is a potential prognostic and predictive biomarker in pancreatic cancer.

Background Liver cancer is one of the most commonly diagnosed cancers across the globe. The treatment is often difficult as it is diagnosed mostly at advanced stages. Moreover, the lack efficacious and less toxic drugs are another problem in the treatment of liver cancer. Against this background, in this study we evaluated the anticancer activity of morusinol against SK-HEP-1 liver cancer cells. Material/Methods The proliferation rate of liver cancer cell line was investigated by MTT assay. Autophagy was detected by transmission electron microscopy and cell cycle analysis was performed by flow cytometry. The protein expression was examined by Western blotting. Results Morusinol inhibited the proliferation of liver cancer SK-HEP-1 cells, with an IC50 of 20 μM against the SK-HEP-1 liver cancer cells. Further investigations indicated that the antiproliferative effects of morusinol are due to initiation of autophagy and G2/M cell cycle arrest, which was also associated with altered expression of several important proteins. Morusinol also suppressed the migration and invasion of SK-HEP-1 liver cancer cells, and it suppressed the expression of p-MEK and p-ERK, leading to suppression of the Raf/MEK/ERK signalling cascade. Conclusions We found that morusinol exerts significant anticancer and autophagic effects on liver cancer cells and our results suggest the potential of morusinol in treatment of liver cancer.

Background Aggressive systemic mastocytosis (ASM) is a very rare form of systemic mastocytosis (SM). The diagnosis of ASM requires the presence of SM criteria with C finding and does not meet the criteria for mast cell leukaemia. Herein, we report an ASM case that initially mimicked lymphoma based on clinical and radiographic analyses. Case presentation: A 87-year-old woman was admitted to our hospital due to the enlargement of cervical lymph nodes and weight loss. The lymph node biopsy is infiltrated by neoplastic mast cells with pale, faintly granular cytoplasm, and with reactive eosinophils in the lesions. The infiltrate is often parafollicular in distribution and the remnant of normal follicles can be seen. The neoplastic cell population was subsequently revealed to exhibit differentiation towards the mast cell lineage by expressing CD117 and CD25. Mutation analysis of c-KIT identified D816V mutation in exon 17. Conclusion ASM diagnosis can be challenging due to its rarity. This diagnosis can be confirmed or disregarded using immunohistochemical markers, such as CD117, CD2 and CD25, in combination with molecular analysis (KITD816V).

Background Glomus tumors, as extremely rare tumors of the lung, since their rarity and the variety of the clinical symptoms, tend to be misdiagnosed. The location of these tumors as well as their early diagnosis is a pivot for the prognosis of the disease. Case presentation We report a case of old patient whose final diagnosis was primary pulmonary glomus tumor. She initially was found a nodule in the right lung, which was enlarged during follow-up and finally confirmed after surgery. Postoperative pathology was considered as a primary pulmonary glomus tumor. There has been no evidence of tumor recurrence or metastasis so far. Conclusion Primary pulmonary glomus tumor is rare. The clinical manifestations are related symptoms occupying lesions in the lung. The diagnosis of the tumor depends on histopathology and immunohistochemistry. Surgical resection is considered as the most effective treatment for this condition.

As one kind of the most important carbon (C) sink in the world, peatlands are sensitive to climate change. The decomposition of litter plays an important role in C fixation and nutrient utilization in peatlands. To reveal the mechanism of response of the litter decomposition to climate warming and the addition of nitrogen (N) in permafrost peatlands, we selected two typical plants, Eriophorum vaginatum and Sphagnum palustre, in the permafrost peatland of Da Xing’anling Mountains, China, as the research objects and conducted a 54-day litter decomposition experiment at 10 ℃ and 20 ℃. Three N addition treatments (CK: 0 mg N g−1, N1: 2.5 mg N g−1, and N2: 5 mg N g−1) were established. Our results showed that the E. vaginatum litter decomposed more quickly than that of Sphagnum, and an increase in temperature significantly promoted the litter decomposition and CO2 emission of E. vaginatum and Sphagnum. The addition of N promoted the decomposition of E. vaginatum litter, whereas the decomposition of Sphagnum litter was promoted by the N1 treatment but was inhibited by the N2 treatment. The enzyme activity in both types of litter was inhibited with the increase in temperature. The abundances of bacteria and fungi positively correlated with the decomposition constant and mean CO2 release rate by E. vaginatum and Sphagnum litter, indicating that the effects of temperature and N addition on the decomposition of plant litter were primarily regulated by microorganisms. This study provides a theoretical basis to understand and predict the effects of global climate change on the decomposition of plant litter in boreal peatlands.

Permafrost peatlands are important pools of soil carbon. Soil organic carbon (SOC) mineralization and its temperature sensitivity in permafrost peatlands are crucial for predictions of soil carbon-climate feedback. However, little is known about the changes in SOC mineralization and its mechanism in response to environmental change in the permafrost peatlands of Northeastern China. We collected seven permafrost peatland soils from Greater and Lesser Khingan Mountains in Northeastern China to investigate how the responses of microbes and labile substrates control the mineralization of SOC in the laboratory incubation study. The results show that temperature and sampling sites affected the mineralization of SOC. Elevated temperatures significantly increased the rate of carbon mineralization across the peatland soils. The mean sensitivity of SOC mineralization to temperature (Q10 value) was 2.96. The increase in substrate availability and microbial abundance in parallel with the increase in temperature is responsible for the high rates of decomposition of the organic carbon pools. We found that the mineralization of soil carbon positively correlated with the concentrations of soil dissolved organic carbon (DOC), NH4+-N, NO3−-N, as well as the abundances of bacteria, fungi, methanotrophs and nirK denitrifiers. Moreover, the content of DOC positively correlated with the abundances of soil bacteria, methanotrophs and nirK denitrifiers, indicating that the influences of soil microbial abundances on carbon mineralization were strongly mediated by the availability of carbon substrates. Our findings provide novel insights into the effects of increasing temperatures on the relationship between microbial communities and labile substrates and their roles in carbon decomposition in permafrost peatlands.

Soil microbes and enzymes in permafrost peatland are sensitive to temperature changes, which might result in more potential loss of carbon and increase in available nitrogen from permafrost peatlands in a warming world. We previously demonstrated that 3-year warming could affect soil microbial abundance and enzymatic activity. However, soil microbial abundance and enzymatic activity in permafrost peatlands under long-term climate warming is not well understood. Therefore, a 6-year field manipulation experiment was used to assess the impact of long-term warming on soil microbial abundance and enzymatic activity in a permafrost peatland in northeastern China. Results showed that 6-year warming increased the abundance of bacteria in 0 to 15 cm soil under tussock and from shrub rhizosphere, fungi from shrub non-rhizosphere, and archaea under tussock and from the rhizosphere of shrub. These increased microbial abundances could stimulate soil carbon cycling and accelerate soil carbon loss in permafrost peatland under warming. Six-year warming increased methanogen abundance in 0 to 15 cm soil and methanotroph abundance in 15 to 30 cm soil under tussock, indicating that warming could enhance CH4 cycling. Soil nirS-denitrifier abundance from the 0 to 15 cm shrub rhizosphere increased under warming, thereby suggesting that warming stimulated denitrification and N2O emission. β-Glucosidase activity in 0 to 15 cm soil under tussock and from shrub rhizosphere increased, but invertase activity in 15 to 30 cm soil under tussock and from shrub rhizosphere showed opposite tendency under warming. DOC content tended to increase in the 0 to 15 cm rhizosphere soil, but decreased in shrub non-rhizosphere soil. Warming increased NH4+–N content in both rhizosphere and non-rhizosphere soil. Positive correlations between abundances of bacteria, archaea, contents of DOC, and NH4+–N in 0 to 15 cm soil suggest that increases in bacterial and archaeal abundance could indicate higher carbon and nitrogen availability in topsoil of permafrost peatlands under warming. The results offer new insights into the response of plant–soil-microbe interactions in permafrost peatlands to climate change.

Peatlands in permafrost region are large carbon pools sensitive to global warming. However, the effects of increased temperature on carbon emissions and associated microbial abundances of peatlands under anaerobic condition remain largely unknown, especially when considering depths. For supplementing the deficiency about this, we collected soil from 0 to 150 cm depth of a permafrost peatland in the Great Hing'an Mountain and incubated at 5 and 15 °C for 55 days under anaerobic condition. Soil CO2 and CH4 emissions were detected during incubation, and inorganic nitrogen, dissolved organic carbon, and carbon-cycling microbial abundances were analyzed at the end of incubation. Results showed that emission rates and cumulative emissions amount of CO2 and CH4 at 15 °C across all soil depths were higher than those observed at 5 °C. Specifically, 0–20 cm and 20–40 cm layers had the highest CO2 emission rates and cumulative emission amounts, whereas the 40–60 cm and 60–80 cm layers had the highest CH4 emission rates and cumulative emission amounts. Mean temperature sensitivity (Q10) values of CO2 and CH4 were 2.39 and 55.49 respectively. Q10 values of bacteria, fungi, archaea, methanogen, and methanotroph abundances were 1.17, 3.85, 1.75, 1.68, and 1.66 respectively, which were calculated by the abundance ratio of microbial functional gene at 15 °C and 5 °C. Similar to the trend of CO2 emissions, high bacteria, fungi, archaea, methanogen, and methanotroph functional gene abundances were also observed in 0–20 cm and 20–40 cm layers, and such abundances increased along with temperature increasing. In sum, elevated temperature enhances the carbon emission of peatland in permafrost region, and the warming simulated CO2 emission is linked to the abundances of carbon-cycling microorganisms.

Soil microbial abundance, which is related to soil characteristics and process rates, is an early indicator of changes in soil health and quality. However, microbial functional groups in permafrost peatland soils have rarely been studied. These soils are important C and N stores and possibly vulnerable to climate warming. We randomly gathered surface soils (0–15 cm and 15–30 cm soil layers) from 10 peatlands in sporadic island, discontinuous island, and continuous permafrost regions in Northeast China. The aim was to clarify the soil microbial abundance distribution in different types of permafrost peatlands. Results revealed different effects of permafrost types on different soil C- and N-cycling microbial abundances in peatlands. The bacteria, amoA, and nirK gene abundances in the two soil layers were the highest in discontinuous island permafrost peatlands. Soil mcrA and pmoA gene abundances in 0–15 cm soil were high in continuous and discontinuous island permafrost peatlands, respectively. The amoA gene abundance in both soil layers and nirS gene abundance in 15–30 cm soil were high in discontinuous island permafrost peatlands. The average nirK gene abundance in both soil layers was in the order: discontinuous island permafrost peatlands > continuous permafrost peatlands > sporadic island permafrost peatlands. No significant differences in archaeal abundance were observed in both soil layers among the different types of permafrost peatlands. Moreover, 42.5%, 15.9%, and 15.3% of the variation in soil microbial abundances could be explained by soil ammonia-N, pH, and total C, respectively. Our results imply that soil microbial abundance can be utilized as effective soil N availability, C pool, and pH indicators in permafrost peatlands.

New radiosensitizers are urgently needed for radiation therapy patients with localized hepatocellular carcinoma (HCC) that is refractory to radical surgery. We previously found that genistein, a major soy isoflavone, exerts radioprotective effects on L-02 normal liver cells at low concentrations. Here, we report that 5 µM genistein shows less harm to L-02 cells than HCC cells and that it significantly enhances the radiosensitivity of HCC cells by enhancing DNA damage, chromosomal aberrations and cell cycle arrest at G2/M phase and by exacerbating apoptosis. Mechanistically, genistein aggravates X-ray-induced decreases in the levels of phospho-Bad (Ser136) but enhances the levels of phospho-Chk2 (Thr68), phospho-ATM (Ser1981) and γ-H2AX. Micro-array analysis indicated that downregulation of POU6F and CCNE2 expression and upregulation of FBXO32 and cyclin B1 expression might play vital roles in genistein-induced radiosensitivity. These findings suggest genistein as an interesting candidate for adjuvant radiotherapy for HCC and indicate that genistein causes less harm to normal cells than HCC cells by inducing G2/M arrest and apoptosis.

In eukaryotic cells, the s oluble N -ethylmaleimide- s ensitive f actor (NSF) a ttachment protein re ceptor (SNARE) proteins comprise the minimal machinery that triggers fusion of transport vesicles with their target membranes. Comparative studies revealed that genes encoding the components of the SNARE system are highly conserved in yeast, insect, and human genomes. Upon infection of insect cells by the virus Autographa californica multiple nucleopolyhedrovirus (AcMNPV), the transcript levels of most SNARE genes initially were upregulated. We found that overexpression of dominant-negative (DN) forms of NSF or knockdown of the expression of NSF, the key regulator of the SNARE system, significantly affected infectious AcMNPV production. In cells expressing DN NSF, entering virions were trapped in the cytoplasm or transported to the nucleus with low efficiency. The presence of DN NSF also moderately reduced trafficking of the viral envelope glycoprotein GP64 to the plasma membrane but dramatically inhibited production of infectious budded virions (BV). Transmission electron microscopy analysis of infections in cells expressing DN NSF revealed that progeny nucleocapsids were retained in a perinuclear space surrounded by inner and outer nuclear membranes. Several baculovirus conserved (core) proteins (Ac76, Ac78, GP41, Ac93, and Ac103) that are important for infectious budded virion production were found to associate with NSF, and NSF was detected within the assembled BV. Together, these data indicate that the cellular SNARE system is involved in AcMNPV infection and that NSF is required for efficient entry and nuclear egress of budded virions of AcMNPV. IMPORTANCE Little is known regarding the complex interplay between cellular factors and baculoviruses during viral entry and egress. Here, we examined the cellular SNARE system, which mediates the fusion of vesicles in healthy cells, and its relation to baculovirus infection. Using a DN approach and RNA interference knockdown, we demonstrated that a general disruption of the SNARE machinery significantly inhibited the production of infectious BV of AcMNPV. The presence of a DN NSF protein resulted in low-efficiency entry of BV and the retention of progeny nucleocapsids in the perinuclear space during egress. Combined with these effects, we also found that several conserved (core) baculovirus proteins closely associate with NSF, and these results suggest their involvement in the egress of BV. Our findings are the first to demonstrate that the SNARE system is required for efficient entry of BV and nuclear egress of progeny nucleocapsids of baculoviruses.

Supplemental Digital Content is available in the text, Nasal-type natural killer/T-cell (NK/T-cell) lymphoma is a more aggressive sub-group of non-Hodgkin lymphoma, which is more common in Asia. The phosphatase and tensin homolog (PTEN) was originally discovered as a candidate tumor suppressor mutated and lost in various cancers. However, its clinical value and role in NK/T-cell lymphoma remain to be further explored. In the present study, we analyzed PTEN protein expression in 60 cases of human NK/T-cell lymphoma tissues and 40 cases of control nasal mucosa tissues specimens by immunohistochemical analysis. As a result, positive rate of PTEN protein expression in NK/T-cell lymphoma tissues (33.3%) is significantly lower than that of control nasal mucosa tissues (85.0%) (P .05). Instead, PTEN protein was inversely corrected with Ki-67 expression, indicating a functional role in PTEN in human NK/T-cell lymphoma (P

Global warming is likely to influence the soil microorganisms and enzyme activity and alter the carbon and nitrogen balance of peatland ecosystems. To investigate the difference in sensitivities of carbon and nitrogen cycling microorganisms and enzyme activity to warming, we conducted three-year warming experiments in a boreal peatland. Our findings demonstrated that both mcrA and nirS gene abundance in shallow soil and deep soil exhibited insensitivity to warming, while shallow soil archaea 16S rRNA gene and amoA gene abundance in both shallow soil and deep soil increased under warming. Soil pmoA gene abundance of both layers, bacterial 16S rRNA gene abundance in shallow soil, and nirK gene abundance in deep soil decreased due to warming. The decreases of these gene abundances would be a result of losing labile substrates because of the competitive interactions between aboveground plants and underground soil microorganisms. Experimental warming inhibited β-glucosidase activity in two soil layers and invertase activity in deep soil, while it stimulated acid phosphatase activity in shallow soil. Both temperature and labile substrates regulate the responses of soil microbial abundances and enzyme activities to warming and affect the coupling relationships of carbon and nitrogen. This study provides a potential microbial mechanism controlling carbon and nitrogen cycling in peatland under climate warming.

As a powerful and object-oriented graphical modeling language, Unified Modeling Language (UML) has been introduced into the design and development of safety-critical computer systems. However, UML model is difficult to reflect the concurrency and consistency of constraint rules between objects and impossible to completely demonstrate the dynamic behavior characteristics of a system. Further, it cannot be directly expressed and analyzed by mathematical tools. Petri net modeling technology uses graphical element place and transition to clearly describe the internal interactions of a system. Meanwhile, Petri net has mature mathematical analysis methods. We have proposed to combine these two tools for designing and analyzing a system with a set of transformation rules from UML statecharts to Petri net. In this paper, an automatic conversion tool is introduced. The tool performs the transformation with three steps as follows: (1) Transforming UML model into XML document, which makes information extraction of the UML model become easier. (2) Analyzing semantics of UML model and Petri net model, then designing data structure for transformation, and completing the transformation based on the transformation rules. (3) Analyzing the transformed Petri net model to verify the characteristics of the UML model. The transformation rules and the tools are developed based on a new railway interlocking system.