Neoadjuvant chemotherapy plus camrelizumab for locally advanced cervical cancer (NACI study): a multicentre, single-arm, phase 2 trial.

BACKGROUND: Locally advanced cervical cancer constitutes around 37% of cervical cancer cases globally and has a poor prognosis due to limited therapeutic options. Immune checkpoint inhibitors in the neoadjuvant setting could address these challenges. We aimed to investigate the efficacy and safety of neoadjuvant chemo-immunotherapy for locally advanced cervical cancer. METHODS: In this single-arm, phase 2 trial, which was done across eight tertiary hospitals in China, we enrolled patients aged 18-70 years with untreated cervical cancer (IB3, IIA2, or IIB/IIIC1r with a tumour diameter ≥4 cm [International Federation of Gynecology and Obstetrics, 2018]) and an Eastern Cooperative Oncology Group performance status of 0 or 1. Eligible patients underwent one cycle of priming doublet chemotherapy (75-80 mg/m2 cisplatin, intravenously, plus 260 mg/m2 nab-paclitaxel, intravenously), followed by two cycles of a combination of chemotherapy (cisplatin plus nab-paclitaxel) on day 1 with camrelizumab (200 mg, intravenously) on day 2, with a 3-week interval between treatment cycles. Patients with stable disease or progressive disease received concurrent chemoradiotherapy, and patients with a complete response or partial response proceeded to radical surgery. The primary endpoint was the objective response rate, by independent central reviewer according to Response Evaluation Criteria in Solid Tumours, version 1.1. Activity and safety were analysed in patients who received at least one dose of camrelizumab. This study is registered with ClinicalTrials.gov, NCT04516616, and is ongoing. FINDINGS: Between Dec 1, 2020, and Feb 10, 2023, 85 patients were enrolled and all received at least one dose of camrelizumab. Median age was 51 years (IQR 46-57) and no data on race or ethnicity were collected. At data cutoff (April 30, 2023), median follow-up was 11·0 months (IQR 6·0-14·5). An objective response was noted in 83 (98% [95% CI 92-100]) patients, including 16 (19%) patients who had a complete response and 67 (79%) who had a partial response. The most common grade 3-4 treatment-related adverse events during neoadjuvant chemo-immunotherapy were lymphopenia (21 [25%] of 85), neutropenia (ten [12%]), and leukopenia (seven [8%]). No serious adverse events or treatment-related deaths occurred. INTERPRETATION: Neoadjuvant chemo-immunotherapy showed promising antitumour activity and a manageable adverse event profile in patients with locally advanced cervical cancer. The combination of neoadjuvant chemo-immunotherapy with radical surgery holds potential as a novel therapeutic approach for locally advanced cervical cancer. FUNDING: National Key Technology Research and Development Program of China and the National Clinical Research Center of Obstetrics and Gynecology.

Radiomic signatures reveal multiscale intratumor heterogeneity associated with tissue tolerance and survival in re-irradiated nasopharyngeal carcinoma: a multicenter study.

BACKGROUND: Post-radiation nasopharyngeal necrosis (PRNN) is a severe adverse event following re-radiotherapy for patients with locally recurrent nasopharyngeal carcinoma (LRNPC) and associated with decreased survival. Biological heterogeneity in recurrent tumors contributes to the different risks of PRNN. Radiomics can be used to mine high-throughput non-invasive image features to predict clinical outcomes and capture underlying biological functions. We aimed to develop a radiogenomic signature for the pre-treatment prediction of PRNN to guide re-radiotherapy in patients with LRNPC. METHODS: This multicenter study included 761 re-irradiated patients with LRNPC at four centers in NPC endemic area and divided them into training, internal validation, and external validation cohorts. We built a machine learning (random forest) radiomic signature based on the pre-treatment multiparametric magnetic resonance images for predicting PRNN following re-radiotherapy. We comprehensively assessed the performance of the radiomic signature. Transcriptomic sequencing and gene set enrichment analyses were conducted to identify the associated biological processes. RESULTS: The radiomic signature showed discrimination of 1-year PRNN in the training, internal validation, and external validation cohorts (area under the curve (AUC) 0.713-0.756). Stratified by a cutoff score of 0.735, patients with high-risk signature had higher incidences of PRNN than patients with low-risk signature (1-year PRNN rates 42.2-62.5% vs. 16.3-18.8%, P < 0.001). The signature significantly outperformed the clinical model (P < 0.05) and was generalizable across different centers, imaging parameters, and patient subgroups. The radiomic signature had prognostic value concerning its correlation with PRNN-related deaths (hazard ratio (HR) 3.07-6.75, P < 0.001) and all causes of deaths (HR 1.53-2.30, P < 0.01). Radiogenomics analyses revealed associations between the radiomic signature and signaling pathways involved in tissue fibrosis and vascularity. CONCLUSIONS: We present a radiomic signature for the individualized risk assessment of PRNN following re-radiotherapy, which may serve as a noninvasive radio-biomarker of radiation injury-associated processes and a useful clinical tool to personalize treatment recommendations for patients with LANPC.

OTUB1 alleviates NASH through inhibition of the TRAF6-ASK1 signaling pathways.

BACKGROUND AND AIMS: NAFLD is considered as the hepatic manifestation of the metabolic syndrome, which includes insulin resistance, obesity and hyperlipidemia. NASH is a progressive stage of NAFLD with severe hepatic steatosis, hepatocyte death, inflammation, and fibrosis. Currently, no pharmacological interventions specifically tailored for NASH are approved. Ovarian tumor domain, ubiquitin aldehyde binding 1 (OTUB1), the founding member of deubiquitinases, regulates many metabolism-associated signaling pathways. However, the role of OTUB1 in NASH is unclarified. METHODS AND RESULTS: We demonstrated that mice with Otub1 deficiency exhibited aggravated high-fat diet-induced and high-fat high-cholesterol (HFHC) diet-induced hyperinsulinemia and liver steatosis. Notably, hepatocyte-specific overexpression of Otub1 markedly alleviated HFHC diet-induced hepatic steatosis, inflammatory responses, and liver fibrosis. Mechanistically, we identified apoptosis signal-regulating kinase 1 (ASK1) as a key candidate target of OTUB1 through RNA-sequencing analysis and immunoblot analysis. Through immunoprecipitation-mass spectrometry analysis, we further found that OTUB1 directly bound to tumor necrosis factor receptor-associated factor 6 (TRAF6) and suppressed its lysine 63-linked polyubiquitination, thus inhibiting the activation of ASK1 and its downstream pathway. CONCLUSIONS: OTUB1 is a key suppressor of NASH that inhibits polyubiquitinations of TRAF6 and attenuated TRAF6-mediated ASK1 activation. Targeting the OTUB1-TRAF6-ASK1 axis may be a promising therapeutic strategy for NASH.

Biomimetic Polylactic Acid Electrospun Fibers Grafted with Polyethyleneimine for Highly Efficient Methyl Orange and Cr(VI) Removal.

The rapid growth of industrialization has resulted in the release of large quantities of pollutants into the environment, especially dyes and heavy metals, which are environmentally hazardous for humans and animals. It is considered as the most promising and environmentally friendly route to develop green materials by using the green modification method, which has no negative impact on the environment. In this work, the green material of polylactic acid (PLA) was used as the substrate material, and a novel modification method of polydopamine (PDA)-assisted polyethyleneimine (PEI) grafting was developed. The electrospun PLA fibers are mainly composed of stereocomplex crystallites, which were achieved via the electrospinning of poly(l-lactic acid) and poly(d-lactic acid). The water-soluble PEI was grafted onto the PDA-modified PLA fibers through the glutaraldehyde-assisted cross-linking reaction. The prepared composite fibers can be degraded, which is environmentally friendly and meets the requirements of sustainable development. The potential application of such PLA composite fibers in wastewater treatment was intensively evaluated. The results show that at appropriate fabrication conditions (PDA concentration of 3 g·L-1 and a PEI molecular weight of 70,000 g·mol-1), the composite fibers exhibit the maximum adsorption capacities of 612 and 398.41 mg·g-1 for methyl orange (MO) and hexavalent chromium [Cr(VI)], respectively. Simultaneously, about 64.79% of Cr(VI) adsorbed on the composite fibers was reduced to Cr(III). The above results show that the PLA composite fibers have a good development prospect in the field of wastewater treatment.

Cutaneous nerve fibers participate in the progression of psoriasis by linking epidermal keratinocytes and immunocytes.

Recent studies have illustrated that psoriatic lesions are innervated by dense sensory nerve fibers. Psoriatic plaques appeared to improve after central or peripheral nerve injury. Therefore, the nervous system may play a vital role in psoriasis. We aimed to clarify the expression of nerve fibers in psoriasis and their relationship with immune cells and keratinocytes, and to explore the effect of skin nerve impairment. Our results illustrated that nerve fibers in psoriatic lesions increased and were closely innervated around immune cells and keratinocytes. RNA-seq analysis showed that peripheral sensory nerve-related genes were disrupted in psoriasis. In spinal cord hemi-section mice, sensory impairment improved psoriasiform dermatitis and inhibited the abnormal proliferation of keratinocytes. Botulinum toxin A alleviated psoriasiform dermatitis by inhibiting the secretion of calcitonin gene-related peptide. Collectively, cutaneous nerve fibers participate in the progression of psoriasis by linking epidermal keratinocytes and immunocytes. Neurological intervention may be a new treatment strategy for psoriasis.

Prognostic significance of AKR1C4 and the advantage of combining EBV DNA to stratify patients at high risk of locoregional recurrence of nasopharyngeal carcinoma.

BACKGROUND: Distinguishing patients at a greater risk of recurrence is essential for treating locoregional advanced nasopharyngeal carcinoma (NPC). This study aimed to explore the potential of aldo-keto reductase 1C4 (AKR1C4) in stratifying patients at high risk of locoregional relapse. METHODS: A total of 179 patients with locoregionally advanced NPC were grouped by different strategies; they were: (a) divided into two groups according to AKR1C4 expression level, and (b) classified into three clusters by integrating AKR1C4 and Epstein-Barr virus (EBV) DNA. The Kaplan-Meier method was used to calculate locoregional relapse-free survival (LRFS), overall survival (OS), progression-free survival (PFS), and distant metastasis-free survival (DMFS). The Cox proportional hazards model was used to determine potential prognostic factors, and a nomogram was generated to predict 3-year and 5-year LRFS. RESULTS: A significant difference in the 5-year LRFS was observed between the high and low AKR1C4 expression groups (83.3% vs. 92.7%, respectively; p = 0.009). After integrating AKR1C4 expression and EBV DNA, the LRFS (84.7%, 84.5%, 96.9%, p = 0.014) of high-, intermediate-, and low- AKR1C4 and EBV DNA was also significant. Multivariate analysis indicated that AKR1C4 expression (p = 0.006) was an independent prognostic factor for LRFS. The prognostic factors incorporated into the nomogram were AKR1C4 expression, T stage, and EBV DNA, and the concordance index of the nomogram for locoregional relapse was 0.718. CONCLUSIONS: In conclusion, high AKR1C4 expression was associated with a high possibility of relapse in NPC patients, and integrating EBV DNA and AKR1C4 can stratify high-risk patients with locoregional recurrence.

First-Line Immunochemotherapy Versus Palliative Chemotherapy Plus Definitive Radiation Therapy for de novo Metastatic Nasopharyngeal Carcinoma: A Matched Cohort Study.

BACKGROUND: The combined use of immune checkpoint inhibitors (ICIs) with palliative chemotherapy (PCT) is a promising first-line treatment for de novo metastatic nasopharyngeal carcinoma (mNPC). However, the efficacy of ICIs with PCT vs PCT with definitive radiation therapy (DRT) remain unclear. METHODS: Patients with mNPC who received first-line immunochemotherapy (ICI + PCT) or PCT + DRT were included. Propensity score matching (PSM) was applied to balance potential confounders between patients who did and did not undergo DRT (at a ratio of 1:1). Progression free survival (PFS) and overall survival (OS) were compared between the 2 groups using a log-rank test and Cox proportional hazard model. RESULTS: Among all participants, 149 received ICI + PCT. After PSM, 149 patients were included in the PCT + DRT group. First-line immunochemotherapy was associated with significantly improved PFS (median 9.0 months vs 12.0 months, P < .001) and OS (median 12.5 months vs 19.9 months, P < .001). Subgroup analysis revealed that tumor response to immunochemotherapy, metastatic organs, and number of metastatic sites potentially affected the efficacy of DRT after first-line immunochemotherapy. CONCLUSION: Compared with PCT + DRT, first-line immunochemotherapy was associated with improved PFS and OS in patients with mNPC but not in patients with unfavorable tumor response and metastasis involving the liver, distant nodes, or multiple sites.

Hypothesis generation: Quantitative research to levator ani muscle injury based on MRI texture analysis.

AIM: Patients with pelvic organ prolapse (POP) mostly have injury to the levator ani muscle (LAM). We aimed to assess LAM injury in POP patients by quantifying texture feature (TF) ratios between the LAM and the obturator internus muscle (OIM) using texture analysis. METHODS: This study retrospectively enrolled 32 participants, including 24 patients with POP and eight people with normal pelvic floor muscles. TFs of the LAM and the OIM were extracted using LIFEx version 6.30, and an independent samples t-test was performed to determine TF ratios characterizing LAM injury. After dimension reduction and binary logic analysis, the optimal TF ratio was obtained and the LAM injury quantitative evaluation was proposed. Spearman's correlation was performed to explore the correlations between TF ratios and clinical characteristics. We compared the diagnostic performance of quantitative evaluation and visual evaluation. RESULTS: There were significant differences in 13 TF ratios between the POP and control groups. The area under the receiver operating characteristic curve of the integrated TF ratio was 0.948. Integrated TF ratio was significantly correlated with body mass index, pregnancies, and vaginal deliveries but had no correlation with LAM volume, hiatal area or abortions. Compared with the visual evaluation, the diagnostic accuracy of the quantitative evaluation had improved by 63.2% and 14.3% in the "minor defect" and "major defect" categories, respectively. CONCLUSION: The integrated TF ratio can be used as a new quantifiable index to characterize LAM injury. The TF evaluation provides a potential role in LAM injury noninvasive diagnostic.

Dual Specificity Phosphatase 12 Regulates Hepatic Lipid Metabolism Through Inhibition of the Lipogenesis and Apoptosis Signal-Regulating Kinase 1 Pathways.

Nonalcoholic fatty liver disease (NAFLD) has become the most common cause of chronic liver disease worldwide. Due to the growing economic burden of NAFLD on public health, it has become an emergent target for clinical intervention. DUSP12 is a member of the dual specificity phosphatase (DUSP) family, which plays important roles in brown adipocyte differentiation, microbial infection, and cardiac hypertrophy. However, the role of DUSP12 in NAFLD has yet to be clarified. Here, we reveal that DUSP12 protects against hepatic steatosis and inflammation in L02 cells after palmitic acid/oleic acid treatment. We demonstrate that hepatocyte specific DUSP12-deficient mice exhibit high-fat diet (HFD)-induced and high-fat high-cholesterol diet-induced hyperinsulinemia and liver steatosis and decreased insulin sensitivity. Consistently, DUSP12 overexpression in hepatocyte could reduce HFD-induced hepatic steatosis, insulin resistance, and inflammation. At the molecular level, steatosis in the absence of DUSP12 was characterized by elevated apoptosis signal-regulating kinase 1 (ASK1), which mediates the mitogen-activated protein kinase (MAPK) pathway and hepatic metabolism. DUSP12 physically binds to ASK1, promotes its dephosphorylation, and inhibits its action on ASK1-related proteins, JUN N-terminal kinase, and p38 MAPK in order to inhibit lipogenesis under high-fat conditions. Conclusion: DUSP12 acts as a positive regulator in hepatic steatosis and offers potential therapeutic opportunities for NAFLD.

Integrated metabonomic-proteomic analysis reveals the effect of glucose stress on metabolic adaptation of Lactococcus lactis ssp. lactis CICC23200.

A combined proteomic and metabonomic approach was used to investigate the metabolism of Lactococcus lactis ssp. lactis subjected to glucose stress treatment. A proteomic method was used to determine 1,427 altered proteins, including 278 proteins with increased expression and 255 proteins with decreased expression. A metabonomic approach was adopted to identify 98 altered metabolites, including 62 metabolites with increased expression and 26 metabolites with decreased expression. The integrated analysis indicated that the RNA and DNA mismatch repair process and energy metabolism were enhanced in response to high-glucose stress in L. lactis. Lactococcus lactis responded to glucose stress by up-regulating oxidoreductase activity, which acted on glycosyl bonds, hydrolase activity, and organic acid transmembrane transporter activity. This led to an improvement in the metabolic flux from glucose to pyruvate, lactate, acetate, and maltose. Down-regulation of amino acid transmembrane transporter, aminoacyl-transfer RNA ligase, hydroxymethyl-, formyl-, and related transferase activities resulted in a decrease in the nitrogen metabolism-associated metabolic pathway, which might be related to inhibition of the production of biogenic amines. Overall, we highlight the response of metabolism to glucose stress and provide potential possibilities for the reduced formation of biogenic amines in improved level of sugar in the dairy fermentation industry. Moreover, according to the demand for industrial production, sugar concentration in fermented foods should be higher, or lower, than a set value that is dependent on bacterial strain and biogenic amine yield.

Crystal structure of the crenarchaeal ExoIII AP endonuclease SisExoIII reveals a conserved disulfide bond endowing the protein with thermostability.

AP endonuclease recognizes and cleaves apurinic/apyrimidinic (AP) sites and plays a critical role in base excision repair. Many ExoIII and EndoIV family AP endonucleases have been characterized both biochemically and structurally in Eukaryote and Bacteria. However, relatively fewer have been studied in Euryarchaeota and there is no such report on an AP endonuclease from Crenarchaeota. Here we report, for the first time, the crystal structure of a crenarchaeal ExoIII AP endonuclease, SisExoIII, from Sulfolobus islandicus REY15A. SisExoIII comprises a two-layer core formed by 10 ß-sheets and a shell formed by 9 surrounding α-helices. A disulfide bond connecting ß8 and ß9 is formed by Cys142 and Cys215. This intra-molecular linkage is conserved among crenarchaeal ExoIII homologs and site-directed mutagenesis revealed that it endows the protein with thermostability, however, disruption of the disulfide bond only has a slight effect on the AP endonuclease activity. We also observed that several key residues within the catalytic center including conserved Glu35 and Asn9 show different conformation compared with known ExoIII proteins and form various intra-molecular salt bridges. The protein possesses three putative DNA binding loops with higher flexibility and hydrophobicity than those of ExoIIIs from other organisms. These features may result in low AP endonuclease activity and defect of exonuclease activity of SisExoIII. The study has deepened our understanding in the structural basis of crenarchaeal ExoIII catalysis and clarified a role of the disulfide bond in maintaining protein thermostability.

Influences of anion concentration and valence on dispersion and aggregation of titanium dioxide nanoparticles in aqueous solutions.

Dispersion and aggregation of nanoparticles in aqueous solutions are important factors for safe application of nanoparticles. In this study, dispersion and aggregation of nano-TiO2 in aqueous solutions containing various anions were investigated. The influences of anion concentration and valence on the aggregation size, zeta potential and aggregation kinetics were individually investigated. Results showed that the zeta potential decreased from 19.8 to -41.4mV when PO43- concentration was increased from 0 to 50mg/L, while the corresponding average size of nano-TiO2 particles decreased from 613.2 to 540.3nm. Both SO42- and NO3- enhanced aggregation of nano-TiO2 in solution. As SO42- concentration was increased from 0 to 500mg/L, the zeta potential decreased from 19.8 to 1.4mV, and aggregate sizes increased from 613.2 to 961.3nm. The trend for NO3- fluctuation was similar to that for SO42- although the range of variation for NO3- was relatively narrow. SO42- and NO3- accelerated the aggregation rapidly, while PO43- did so slowly. These findings facilitate the understanding of aggregation and dispersion mechanisms of nano-TiO2 in aqueous solutions in the presence of anions of interest.

Biodegradation of 3,5-dimethyl-2,4-dichlorophenol in saline wastewater by newly isolated Penicillium sp. yz11-22N2.

In this study, the performance of 3,5-dimethyl-2,4-dichlorophenol (DCMX) degradation by a screened strain was investigated. 18S rDNA and the neighbor-joining method were used for identification of the isolated strain. The results of phylogenetic analysis and scanning electron micrographs showed that the most probable identity of the screened strain should be Penicillium sp. Growth characteristics of Penicillium sp. and degradation processes of DCMX were examined. Fourier transform infrared spectroscopy of the inoculated DCMX solution was recorded, which supported the capacity of DCMX degradation by the screened Penicillium sp. Under different salinity conditions, the highest growth rate and removal efficiency for DCMX were obtained at pH6.0. The removal efficiency decreased from 100% to 66% when the DCMX concentration increased from 5 to 60mg/L, respectively. Using a Box-Behnken design, the maximum DCMX removal efficiency was determined to be 98.4%. With acclimation to salinity, higher removal efficiency could be achieved. The results demonstrate that the screened Penicillium sp. has the capability for degradation of DCMX.

Distinct catalytic activity and in vivo roles of the ExoIII and EndoIV AP endonucleases from Sulfolobus islandicus.

AP endonuclease cleaves the phosphodiester bond 5'- to the AP (apurinic or apyrimidinic) sites and is one of the major enzymes involved in base excision repair. So far, the properties of several archaeal AP endonuclease homologues have been characterized in vitro, but little is known about their functions in vivo. Herein, we report on the biochemical and genetic analysis of two AP endonucleases, SisExoIII and SisEndoIV, from the hyperthermophilic crenarchaeon Sulfolobus islandicus REY15A. Both SisExoIII and SisEndoIV exhibit AP endonuclease activity, but neither of them has 3'-5' exonuclease activity. SisExoIII and SisEndoIV have similar K M values on the substrate containing an AP site, but the latter cleaves the AP substrate at a dramatically higher catalytic rate than the former. Unlike other AP endonucleases identified in archaea, SisExoIII and SisEndoIV do not exhibit any cleavage activity on DNA having oxidative damage (8-oxo-dG) or uracil. Genetic analysis revealed that neither gene is essential for cell viability, and the growth of ∆SiRe_2666 (endoIV), ∆SiRe_0100 (exoIII), and ∆SiRe_0100∆SiRe_2666 is not affected under normal growth conditions. However, ∆SiRe_2666 exhibits higher sensitivity to the alkylating agent methyl methanesulfonate (MMS) than ∆SiRe_0100. Over-expression of SiRe_0100 can partially complement the sensitivity of ∆SiRe_2666 to MMS, suggesting a backup role of SisExoIII in AP site processing in vivo. Intriguingly, over-expression of SisEndoIV renders the strain more sensitive to MMS than the control. Taken together, we conclude that SisEndoIV, but not SisExoIII, is the main AP endonuclease that participates directly in base excision repair in S. islandicus.

Associations between recent gay-related stressful events, emotional distress, social support and unprotected anal intercourse behavior among Chinese men who have sex with men.

BACKGROUND: This study was designed to assess the levels of and associations between gay-related stressful events, social support, emotional distress and the number of unprotected anal intercourse partners among Chinese men who have sex with men. METHODS: Using a respondent-driven sampling method, 807 men who have sex with men were recruited in urban areas of northeast China and data were collected via face-to-face interviews. Gay-related stressful events were measured using the Gay-Related Stressful Life Events Scale; levels of depression, anxiety symptoms and social support were measured using the Self-Rating Depression Scale, the Self-Rating Anxiety Scale and the Social Support Rating Scale, respectively. RESULTS: Over a quarter of study participants experienced gay-related stressful events during the preceding 3 months. Their average Self-Rating Depression Scale, Self-Rating Anxiety Scale and Social Support scores differed significantly from the national norm. Gay-related stressful events significantly correlated with anxiety (r = 0.167, p < 0.001), depression (r = 0.165, p < 0.001), social support (r = -0.107, p = 0.002) and number of unprotected anal intercourse partners (r = 0.13, p < 0.001), showing a clear dose-response relationship. CONCLUSION: Gay-related stressful events are common and are significantly associated with emotional distress, lack of social support and high-risk sexual behaviors among Chinese men who have sex with men. Multifaceted approaches are warranted to increase social support and reduce intolerance toward homosexual behaviors and to reduce risky sexual behaviors related to the rapid HIV epidemic among men who have sex with men population in China.

Multi-pulse time delay integration method for flexible 3D super-resolution range-gated imaging.

Constructing flexible regular-shaped range-intensity profiles by the convolution of illuminator laser pulse and sensor gate pulse is crucial for 3D super-resolution range-gated imaging. However, ns-scale rectangular-shaped laser pulse with tunable pulse width is difficult to be obtained, especially for pulsed solid-stated lasers. In this paper we propose a multi-pulse time delay integration (MPTDI) method to reshape range-intensity profiles (RIP) free from the above limitation of pulsed lasers. An equivalent laser pulse temporal shaping model is established to evaluate and optimize the MPTDI method. By using MPTDI, the RIP shape and depth of viewing can both be flexibly changed as desired. Here typical triangular and trapezoidal RIPs are established for 3D imaging under triangular and trapezoidal range-intensity correlation algorithms. In addition, a prototype experiment is demonstrated to prove the feasibility of MPTDI.

Role of Yes-associated protein 1 in gliomas: pathologic and therapeutic aspects.

The activation of proline-rich phosphoprotein Yes-associated protein 1 (YAP1) possesses a possible link between stem/progenitor cells, organ size, and cancer. YAP1 has been indicated as an oncoprotein, and overexpression of YAP1 is reported in many human brain tumors, including infiltrating gliomas. During normal brain development, the neurofibromatosis 2 (NF2) protein suppresses YAP1 activity in neural progenitor cells to promote guidepost cell differentiation, but loss of NF2 causes elevating YAP1 activity in midline neural progenitors, which disrupts guidepost formation. Overexpression of endogenous CD44 (cancer stem cell marker) promotes phosphorylation/inactivation of NF2, and upregulates YAP1 expression and leads to cancer cell resistance in glioblastoma. The hippo pathway is also related to the YAP1 action. However, the mechanism of YAP1 action in glioma is still far from clear understanding. Advances in clinical management based on an improved understanding of the function of YAP1 may help to serve as a molecular target in glioma therapeutics. Knockdown of YAP1 by shRNA technology has been shown to reduce glioma in vitro; however, clinical implications are still under investigation. YAP1 can be used as a diagnostic marker for gliomas to monitor the disease status and may help to evaluate its treatment effects. More functional experiments are needed to support the direct roles of YAP1 on gliomas at molecular and cellular levels.

Laparoscopy versus laparotomy for the management of early stage cervical cancer.

BACKGROUND: The possible advantages of laparoscopic radical hysterectomy (LRH) versus open radical hysterectomy (RH) have not been well reviewed systematically. The aim of this study was to systematically review the comparative effectiveness between LRH and RH in the treatment of cervical cancer based on the evaluation of the Perioperative outcomes, oncological clearance, complications and long-term outcomes. METHODS: The systematic review was conducted by searching PubMed, MEDLINE, EMBASE, the Cochrane Library and BIOSIS databases. All original studies that compared LRH with RH were included for critical appraisal. Data were pooled and analyzed. RESULTS: A total of twelve original studies that compared LRH (n = 754) with RH (n = 785) in patients with cervical cancer fulfilled quality criteria were selected for review and meta-analysis. LRH compared with RH was associated with a significant reduction of intraoperative blood loss (weighted mean difference = -268.4 mL (95 % CI -361.6, -175.1; p < 0.01), a reduced risk of postoperative complications (OR = 0.46; 95 % CI 0.34-0.63) and shorter hospital stay (weighted mean difference = -3.22 days; 95 % CI-4.21, -2.23 days; p < 0.01). These benefits were at the cost of longer operative time (weighted mean difference = 26.9 min (95 % CI 8.08-45.82). The rate of intraoperative complications was similar in the two groups. Lymph nodes yield and positive resection margins were similar between the two groups. There were no significant differences in 5-year overall survival (HR 0.91, 95 % CI 0.48-1.71; p = 0.76) and 5-year disease-free survival (hazard ratio [HR] 0.97, 95 % CI 0.56-1.68; p = 0.91). CONCLUSIONS: LRH shows better short term outcomes compared with RH in patients with cervical cancer. The oncologic outcome and 5-year survival were similar between the two groups.

Genetic analysis of the Holliday junction resolvases Hje and Hjc in Sulfolobus islandicus.

The in vivo functions of Hje and Hjc, two Holliday junction resolvases in Sulfolobus islandicus were investigated. We found that deletion of either hje or hjc had no effect on normal cell growth, while deletion of both hje and hjc is lethal. Although Hjc is the conserved resolvase in all archaea, the hje deletion rather than hjc deletion rendered cells more sensitive to DNA-damaging agents such as hydroxyurea, cisplatin, and methyl methanesulfonate than the wild type (WT). Intriguingly, the sensitivity of Δhje could not be rescued by ectopic expression of Hje from a plasmid and Hje overexpression slowed growth and large cells appeared with more than two genome equivalents. We showed that Hje was maintained at a low level in WT cells. Furthermore, transcriptomic microarray analysis revealed that the abundance of transcripts of many genes including those involved in DNA replication, repair, transcription regulation, and cell division changed drastically in the Hje-overexpressed strain. However, only limited genes were up- or downregulated in the hje deletion strain. Our findings collectively suggest that Hje is the primary resolvase involved in DNA repair and its expression must be tightly controlled in cells.

[Er3+:Yb3+ co-doped nanocrystals BaGd2ZnO5 of up-conversion optical temperature sensing].

By far, the most efficient upconversion nanocrystals luminescence materials BaGd2ZnO5: 4%Yb3+ , 1%Er3+, with stable chemical performance, were prepared by using Sol-gel method. XRD pattern shows that the sample is pure phase, belongs to the orthogonal crystals, and space group is Pbnm; SEM micrograph shows that the prepared sample of the morphology sized around 150 nm is evenly distributed. Samples with 971 nm semiconductor laser excitation produce a strong green emission, visible to the naked eye, and uponversion strength and pump energy relation n = 1.22 is two-photon for the realization of the upconversion emission. They originated from Er3+ ions 2H(11/2)--2H(11/2)-->4I(15/2) and 4S(3/2)-->4I(15/2) transition emission, Er3+ ions main excited state absorption (ESA) process is: 4I(15/2)-->4I(11/2)-->2F(7/2)-->2H(11/2), 4S(3/2), Yb3+ was added because of its large absorption cross section (10(4) cm(-1)) so that it is easy to transfer excitation energy to the E3+ ions which enhance the layout particles number and the energy state of the 1F7/2, thereby enhancing the intensity of the peaks of the spectrum. Fluorescence intensity ratio (FIR) technique based on the green upconversion emission of the sample has been studied because the Er3+ ions 2H(11/2) and 4S(3/2) energy level spacing is small. The electrons at the two levels conform to the Boltzmann distribution which is a function of temperature, and thus the fluorescence intensity ratio of two levels can be used to measure the temperature of the substrate material. This method does not interfere with temperature field of the measured object, and can eliminate the uncertainty of the accuracy; the test has a wide temperature range and reasonable temperature resolution, the pump source used is simple, convenient and inexpensive, and has more commercial values. The temperature range of the samples is from 350 to 800 K, and the highest temperature measuring sensitivity can reach 0.0031 K(1). At the same time, under low excitation density, it can produce higher conversion transmission power, making it become ideal material for distance non-contact temperature measurement.