The pattern of relapse and survival of elective irradiation of the upper neck for stage N0 nasopharyngeal carcinoma

<p>Abstract</p> <p>Background</p> <p>To investigate patterns of failure and survival rates of elective irradiation of upper neck in N0 nasopharyngeal carcinoma patients.</p> <p>Methods</p> <p>From February 1996 to November 2002, 97 patients without cervical lymph node involvement were admitted for radiotherapy alone. Before treatment, each patient underwent enhanced CT of nasopharynx and neck. All patients received radiotherapy to the nasopharynx, skull base, and upper neck drainage areas (including levels II, III, and VA). The upper neck was irradiated to a total dose of 50-56 Gy/25-28 fractions/5-5.6 weeks. For the primary tumor, 22 patients used conventional fractionation for a total dose of 70 Gy/35 fractions/7 weeks, and 75 patients used an accelerated hyperfractionationated schedule for a total dose of 78 Gy/60 fractions/6 weeks.</p> <p>Results</p> <p>The median follow-up of these 97 patients was 7.75 years. 10 patients had recurrences in the nasopharynx, 8 had distant metastasis, and 5 had recurrences in the cervical lymph nodes. Among the cervical lymph node failures, the areas of recurrence were in the II drainage areas in 4 patients who had neck dissections afterwards, and in IA drainage areas in 1 patient who also had recurrence in the nasopharynx. The causes of death were recurrence in the nasopharynx for 8 patients, 1 of these also had recurrence in the neck, distant metastases in 8 patients, and non-neoplastic diseases in 3 patients.</p> <p>Conclusions</p> <p>The causes of failure of N0 patients with nasopharyngeal carcinoma after radiotherapy alone to the nasopharynx and upper neck were nasopharyngeal recurrence, distant metastasis, and cervical recurrence in order of frequency. Elective irradiation of upper neck (II, III, VA) is advised for stage N0 patients diagnosed by enhanced CT of neck. Cervical recurrence alone is rare, which did not greatly affect the long-term survival after salvage neck dissection.</p

A \u3ci\u3ecis\u3c/i\u3e-Acting Mutation in the \u3ci\u3ePxABCG1\u3c/i\u3e Promoter Is Associated with Cry1Ac Resistance in \u3ci\u3ePlutella xylostella\u3c/i\u3e (L.)

The molecular mechanisms of insect resistance to Cry toxins generated from the bacterium Bacillus thuringiensis (Bt) urgently need to be elucidated to enable the improvement and sustainability of Bt-based products. Although downregulation of the expression of midgut receptor genes is a pivotal mechanism of insect resistance to Bt Cry toxins, the underlying transcriptional regulation of these genes remains elusive. Herein, we unraveled the regulatory mechanism of the downregulation of the ABC transporter gene PxABCG1 (also called Pxwhite), a functional midgut receptor of the Bt Cry1Ac toxin in Plutella xylostella. The PxABCG1 promoters of Cry1Ac-susceptible and Cry1Ac-resistant strains were cloned and analyzed, and they showed clear differences in activity. Subsequently, a dual-luciferase reporter assay, a yeast one-hybrid (Y1H) assay, and RNA interference (RNAi) experiments demonstrated that a cis-mutation in a binding site of the Hox transcription factor Antennapedia (Antp) decreased the promoter activity of the resistant strain and eliminated the binding and regulation of Antp, thereby enhancing the resistance of P. xylostella to the Cry1Ac toxin. These results advance our knowledge of the roles of cis- and trans-regulatory variations in the regulation of midgut Cry receptor genes and the evolution of Bt resistance, contributing to a more complete understanding of the Bt resistance mechanism

Deterministic Computing Power Networking: Architecture, Technologies and Prospects

With the development of new Internet services such as computation-intensive and delay-sensitive tasks, the traditional "Best Effort" network transmission mode has been greatly challenged. The network system is urgently required to provide end-to-end transmission determinacy and computing determinacy for new applications to ensure the safe and efficient operation of services. Based on the research of the convergence of computing and networking, a new network paradigm named deterministic computing power networking (Det-CPN) is proposed. In this article, we firstly introduce the research advance of computing power networking. And then the motivations and scenarios of Det-CPN are analyzed. Following that, we present the system architecture, technological capabilities, workflow as well as key technologies for Det-CPN. Finally, the challenges and future trends of Det-CPN are analyzed and discussed

The metabolic repression effect of carbon-ion radiotherapy in synchronous hormone-sensitive oligometastatic prostate cancer

BackgroundMetastatic prostate cancer (PCa) poses a significant public health concern. While radiation therapy (RT) is commonly utilized in the treatment of synchronous oligometastatic hormone sensitive prostate cancer (OM-HSPC), the occurrence of biochemical recurrence still remains. To deepen our understanding and optimize the outcome of OM-HSPC, we conducted this study to investigate the characteristics of PCa progression and explore potential synergistic mechanisms involving carbon-ion radiotherapy (CIRT) and neoadjuvant androgen deprivation treatment (naADT) in OM-HSPC.MethodsMetabolomic analysis was conducted with 72 urinary samples (at different timepoints) from 33 Patients (T2-3N0M0-1b) and 18 healthy volunteers by using liquid chromatography-tandem mass spectrometry (LC-MS/MS). MetaboAnalyst website and R software were employed for metabolomic analysis and visualization (using the criteria of p value &lt; 0.05 and |FC|&gt;1.5). The impact of CIRT on metabolism were further verified and explored through in vitro and in vivo experiments.ResultsWe found that most metabolites (223 out of 233) were upregulated in treatment-naïve PCa samples compared to healthy samples. After naADT, 60 core risk metabolites were still significantly related to PCa’s progression, and the glutamine level which was significantly higher in OM-HSPC compared to other groups. Remarkably, after CIRT treatment, the glutamine levels in OM-HSPC were significantly reduced to the level of healthy samples. Experiments further confirmed CIRT’s ability to suppress glutamine levels in PCa tumors and its potential enhancement with glutamine deprivation intervention.ConclusionCIRT with naADT might synergistically inhibit HS-OMPC development, progression and even the ADT resistance through glutamine metabolism repression, moreover, the glutamine metabolism might be a novel target to further improved the efficacy of CIRT

A cis-acting mutation in the PxABCG1 promoter is associated with Cry1Ac resistance in Plutella xylostella (L.)

The molecular mechanisms of insect resistance to Cry toxins generated from the bacterium Bacillus thuringiensis (Bt) urgently need to be elucidated to enable the improvement and sustainability of Bt-based products. Although downregulation of the expression of midgut receptor genes is a pivotal mechanism of insect resistance to Bt Cry toxins, the underlying transcriptional regulation of these genes remains elusive. Herein, we unraveled the regulatory mechanism of the downregulation of the ABC transporter gene PxABCG1 (also called Pxwhite), a functional midgut receptor of the Bt Cry1Ac toxin in Plutella xylostella. The PxABCG1 promoters of Cry1Ac-susceptible and Cry1Ac-resistant strains were cloned and analyzed, and they showed clear differences in activity. Subsequently, a dual-luciferase reporter assay, a yeast one-hybrid (Y1H) assay, and RNA interference (RNAi) experiments demonstrated that a cis-mutation in a binding site of the Hox transcription factor Antennapedia (Antp) decreased the promoter activity of the resistant strain and eliminated the binding and regulation of Antp, thereby enhancing the resistance of P. xylostella to the Cry1Ac toxin. These results advance our knowledge of the roles of cis- and trans-regulatory variations in the regulation of midgut Cry receptor genes and the evolution of Bt resistance, contributing to a more complete understanding of the Bt resistance mechanism

Carbon Ion Radiotherapy Induce Metabolic Inhibition After Functional Imaging-Guided Simultaneous Integrated Boost for Prostate Cancer

PurposeAs local recurrence remains a challenge and the advantages of the simultaneous integrated boost (SIB) technique have been validated in photon radiotherapy, we applied the SIB technique to CIRT. The aim was to investigate the metabolomic changes of the CIRT with concurrent androgen deprivation therapy (ADT) in localized prostate cancer (PCa) and the unique metabolic effect of the SIB technique.Material and MethodsThis study enrolled 24 pathologically confirmed PCa patients. All patients went through CIRT with concurrent ADT. The gross target volume (GTV) boost was defined as positive lesions on both 68Ga-PSMA PET/CT and mpMRI images. Urine samples collected before and after CIRT were analyzed by the Q-TOF UPLC-MS/MS system. R platform and MetDNA were used for peak detection and identification. Statistical analysis and metabolic pathway analysis were performed on Metaboanalyst.ResultsThe metabolite profiles were significantly altered after CIRT. The most significantly altered metabolic pathway is PSMA participated alanine, aspartate and glutamate metabolism. Metabolites in this pathway showed a trend to be better suppressed in the SIB group. A total of 11 identified metabolites were significantly discriminative between two groups and all of them were better down-regulated in the SIB group. Meanwhile, among these metabolites, three metabolites in DNA damage and repair related purine metabolism were down-regulated to a greater extent in the SIB group.ConclusionMetabolic dysfunction was one of the typical characteristics of PCa. CIRT with ADT showed a powerful inhibition of PCa metabolism, especially in PSMA participated metabolic pathway. The SIB CIRT showed even better performance on down-regulation of most metabolism than uniform-dose-distribution CIRT. Meanwhile, the SIB CIRT also showed its unique superiority to inhibit purine metabolism. PSMA PET/CT guided SIB CIRT showed its potentials to further benefit PCa patients

MAPK-activated transcription factor PxJun suppresses PxABCB1 expression and confers resistance to Bacillus thuringiensis Cry1Ac toxin in Plutella xylostella (L.)

Deciphering the molecular mechanisms underlying insect resistance to Cry toxins produced by Bacillus thuringiensis (Bt) is pivotal for the sustainable utilization of Bt biopesticides and transgenic Bt crops. Previously, we identified that MAPK-mediated reduced expression of the PxABCB1 gene is associated with Bt Cry1Ac resistance in the diamondback moth, Plutella xylostella (L.). However, the underlying transcriptional regulation mechanism remains enigmatic. Herein, the PxABCB1 promoter in Cry1Ac-susceptible and Cry1Ac-resistant P. xylostella strains was cloned and analyzed and found to contain a putative Jun binding site (JBS). A dual-luciferase reporter assay and yeast one-hybrid assay (Y1H) demonstrated that the transcription factor PxJun repressed PxABCB1 expression by interacting with this JBS. The expression levels of PxJun were increased in the midguts of all resistant strains compared to the susceptible strain. Silencing of PxJun expression significantly elevated PxABCB1 expression and Cry1Ac susceptibility in the resistant NIL-R strain, and silencing of PxMAP4K4 expression decreased PxJun expression and also increased PxABCB1 expression. These results indicate that MAPK-activated PxJun suppresses PxABCB1 expression to confer Cry1Ac resistance in P. xylostella, deepening our understanding of the transcriptional regulation of midgut Cry receptor genes and the molecular basis of insect resistance to Bt Cry toxins.ImportanceThe transcriptional regulation mechanisms underlying reduced expression of Bt toxin receptor genes in Bt-resistant insects remain elusive. This study unveils that a transcription factor PxJun activated by the MAPK signaling pathway represses PxABCB1 expression and confers Cry1Ac resistance in P. xylostella Our results provide new insights into the transcriptional regulation mechanisms of midgut Cry receptor genes and deepen our understanding of the molecular basis of insect resistance to Bt Cry toxins. To our knowledge, this study identified the first transcription factor that can be involved in the transcriptional regulation mechanisms of midgut Cry receptor genes in Bt-resistant insects

Dynamics behind disjunct distribution, hotspot-edge refugia, and discordant RADseq/mtDNA variability: insights from the Emei mustache toad

Abstract Background The distribution of genetic diversity and the underlying processes are important for conservation planning but are unknown for most species and have not been well studied in many regions. In East Asia, the Sichuan Basin and surrounding mountains constitute an understudied region that exhibits a “ring” of high species richness overlapping the eastern edge of the global biodiversity hotspot Mountains of Southwest China. We examine the distributional history and genetic diversification of the Emei mustache toad Leptobrachium boringii, a typical “ring” element characterized by disjunct ranges in the mountains, by integrating time-calibrated gene tree, genetic variability, individual-level clustering, inference of population splitting and mixing from allele frequencies, and paleoclimatic suitability modeling. Results The results reveal extensive range dynamics, including secondary contact after long-term isolation via westward dispersal accompanied by variability loss. They allow the proposal of a model that combines recurrent contractions caused by Quaternary climatic changes and some failed expansions under suitable conditions for explaining the shared disjunct distribution pattern. Providing exceptional low-elevation habitats in the hotspot area, the eastern edge harbors both long-term refugial and young immigrant populations. This finding and a synthesis of evidence from other taxa demonstrate that a certain contributor to biodiversity, one that preserves and receives low-elevation elements of the east in this case, can be significant for only a particular part of a hotspot. By clarifying the low variability of these refugial populations, we show that discordant mitochondrial estimates of diversity can be obtained for populations that experienced admixture, which would have unlikely left proportional immigrant alleles for each locus. Conclusions Dispersal after long-term isolation can explain much of the spatial distribution of genetic diversity in this species, while secondary contact and long-term persistence do not guarantee a large variation. The model for the formation of disjunct ranges may apply to many other taxa isolated in the mountains surrounding the Sichuan Basin. Furthermore, this study provides insights into the heterogeneous nature of hotspots and discordant variability obtained from genome-wide and mitochondrial data

The Expressions and Mechanisms of Sarcomeric Proteins in Cancers

The sarcomeric proteins control the movement of cells in diverse species, whereas the deregulation can induce tumours in model organisms and occurs in human carcinomas. Sarcomeric proteins are recognized as oncogene and related to tumor cell metastasis. Recent insights into their expressions and functions have led to new cancer therapeutic opportunities. In this review, we appraise the evidence for the sarcomeric proteins as cancer genes and discuss cancer-relevant biological functions, potential mechanisms by which sarcomeric proteins activity is altered in cancer