Trypanosome RNA helicase KREH2 differentially controls non-canonical editing and putative repressive structure via a novel proposed 'bifunctional' gRNA in mRNA A6.

U-insertion/deletion (U-indel) RNA editing in trypanosome mitochondria is directed by guide RNAs (gRNAs). This editing may developmentally control respiration in bloodstream forms (BSF) and insect procyclic forms (PCF). Holo-editosomes include the accessory RNA Editing Substrate Binding Complex (RESC) and RNA Editing Helicase 2 Complex (REH2C), but the specific proteins controlling differential editing remain unknown. Also, RNA editing appears highly error prone because most U-indels do not match the canonical pattern. However, despite extensive non-canonical editing of unknown functions, accurate canonical editing is required for normal cell growth. In PCF, REH2C controls editing fidelity in RESC-bound mRNAs. Here, we report that KREH2, a REH2C-associated helicase, developmentally controls programmed non-canonical editing, including an abundant 3' element in ATPase subunit 6 (A6) mRNA. The 3' element sequence is directed by a proposed novel regulatory gRNA. In PCF, KREH2 RNAi-knockdown up-regulates the 3' element, which establishes a stable structure hindering element removal by canonical initiator-gRNA-directed editing. In BSF, KREH2-knockdown does not up-regulate the 3' element but reduces its high abundance. Thus, KREH2 differentially controls extensive non-canonical editing and associated RNA structure via a novel regulatory gRNA, potentially hijacking factors as a 'molecular sponge'. Furthermore, this gRNA is bifunctional, serving in canonical CR4 mRNA editing whilst installing a structural element in A6 mRNA.

Resolution adjustable Lissajous scanning with piezoelectric MEMS mirrors.

We previously designed a dual-axis piezoelectric MEMS mirror with a low crosstalk gimbal structure, which is utilized as the key device for further research for laser beam scanning. This paper mainly focuses on studying the Lissajous scanning resolution of this MEMS mirror with frequency ratio and phase modulation. For accurately evaluating the scanning resolution, the center angular resolution of Lissajous scanning is redefined by theoretical calculation and verified with experimental measurement. Meanwhile, the scanning nonlinearity of MEMS mirror is studied carefully. Finally, the MEMS mirror works at the state of pseudo-resonance, and the center angular resolution better than 0.16° (H) × 0.03° (V) is achieved at a scanning Field of view (FoV) of 35.0° (H) × 16.5° (V). Moreover, a feasible route of resolution adjustable Lissajous scanning is provided by optimization of frequency ratio and phase modulation, which is helpful for high definition and high frame rate (HDHF) laser scanning imaging with the dual-axis mirror.

Selective Metallization on Ordinary Polymer Substrates by Laser Direct Activation of Copper Phosphate or Nickel Phosphate.

In recent years, selective metallization on polymer surfaces has attracted considerable attention due to its excellent properties and wide applications. This paper reports that copper phosphate (Cu3(PO4)2) or nickel phosphate (Ni3(PO4)2) was selected as laser-active material to successfully fabricate metallic patterns on ordinary polymer substrates by laser direct activation and electroless plating. Scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS) were utilized to characterize the interaction mechanism between a nanosecond-pulsed laser (355 and 1064 nm wavelengths) and Cu3(PO4)2 or Ni3(PO4)2. It was found that after 355 or 1064 nm laser activation with appropriate parameters, Cu+ was generated from Cu3(PO4)2, and NiO was generated from Ni3(PO4)2. At the same time, Cu+ or NiO adsorbed on the porous sponge-like microstructure of modified polycarbonate (PC), respectively, and acted as catalytic active centers to realize selective copper deposition in the laser-activated zone. Furthermore, the obtained copper layers were confirmed to possess good selectivity, electrical conductivity, and high adhesion strength (the highest grade of 5B). Moreover, from comparisons of Cu3(PO4)2 with Ni3(PO4)2 and of 355 nm laser activation with 1064 nm laser activation, the 1064 nm laser activation of Cu3(PO4)2 produced the most catalytic seeds (Cu+) and had the best catalytic effect.

Enhanced therapeutic effect of PEDF-loaded mesenchymal stem cell-derived small extracellular vesicles against oxygen-induced retinopathy through increased stability and penetrability of PEDF.

BACKGROUND: Several common retinal diseases that cause blindness are characterised by pathological neovascularisation accompanied by inflammation and neurodegeneration, including retinopathy of prematurity (ROP), diabetic retinopathy (DR), age-related macular degeneration (AMD), and retinal vein occlusion (RVO). The current treatment strategies for these diseases have limited benefits. Thus, safer and more effective alternative approaches are required. In this study, we loaded small extracellular vesicles (sEVs) derived from mesenchymal stem cell (MSC) with pigment epithelium-derived factor (PEDF), and tested the therapeutic effect of PEDF-loaded sEVs (PEDF-sEVs) using an oxygen induced retinopathy (OIR) mouse model, aiming to establish a new therapy strategy for the treatment of retinal pathological angiogenesis. RESULTS: We formulated PEDF-loaded sEVs (PEDF-sEVs) containing high concentrations of PEDF and evaluated their effects through in vivo and in vitro experiments. In OIR mice, PEDF-sEVs showed significantly better effects on retinal avascular areas, inflammation, and neuronal degeneration compared with the anti-vascular endothelial growth factor (VEGF) drug, which may indicate a possible advantage of PEDF-sEVs over anti-VEGF drugs in the treatment of pathological neovascularisation. In vitro, PEDF-sEVs greatly inhibited endothelial cell (EC) proliferation, migration, and tube formation by suppressing the VEGF-induced phosphorylation of extracellular signal-regulated kinase (ERK) and AKT (also known as Protein Kinase B). All experiments and analyses were performed in triplicate. PEDF-sEVs were more effective than PEDF or sEVs alone, both in vitro and in vivo. Furthermore, to determine the distribution of PEDF-sEVs, we used DiD-labelled sEVs and FITC-labelled PEDF to track the sEVs and PEDF, respectively. We found that PEDF-sEVs effectively reduced the degradation of PEDF. CONCLUSIONS: Loading PEDF on sEVs effectively enhanced the anti-angiogenic, anti-inflammatory, and neuroprotective effects of PEDF by increasing the stability and penetrability. These results suggest a potential role for PEDF-sEVs in retinal pathological neovascularisation.

Deep learning-based postoperative visual acuity prediction in idiopathic epiretinal membrane.

BACKGROUND: To develop a deep learning (DL) model based on preoperative optical coherence tomography (OCT) training to automatically predict the 6-month postoperative visual outcomes in patients with idiopathic epiretinal membrane (iERM). METHODS: In this retrospective cohort study, a total of 442 eyes (5304 images in total) were enrolled for the development of the DL and multimodal deep fusion network (MDFN) models. All eyes were randomized into a training dataset with 265 eyes (60.0%), a validation dataset with 89 eyes (20.1%), and an internal testing dataset with the remaining 88 eyes (19.9%). The input variables for prediction consisted of macular OCT images and diverse clinical data. Inception-Resnet-v2 network was utilized to estimate the 6-month postoperative best-corrected visual acuity (BCVA). Concurrently, a regression model was developed using the clinical data and OCT parameters in the training data set for predicting postoperative BCVA. The reliability of the models was subsequently evaluated using the testing dataset. RESULTS: The prediction DL algorithm exhibited a mean absolute error (MAE) of 0.070 logMAR and root mean square error (RMSE) of 0.11 logMAR in the testing dataset. The DL model demonstrated a robust promising performance with R2 = 0.80, notably superior to R2 = 0.49 of the regression model. The percentages of BCVA prediction errors within ± 0.20 logMAR amounted to 94.32% in the testing dataset. CONCLUSIONS: The OCT-based DL model demonstrated sensitivity and accuracy in predicting postoperative BCVA in iERM patients. This innovative DL model exhibits substantial potential for integration into surgical planning protocols.

Molecular Mechanisms of Oxidative Stress Relief by CAPE in ARPE-19 Cells.

Caffeic acid phenylethyl ester (CAPE) is an antioxidative agent originally derived from propolis. Oxidative stress is a significant pathogenic factor in most retinal diseases. Our previous study revealed that CAPE suppresses mitochondrial ROS production in ARPE-19 cells by regulating UCP2. The present study explores the ability of CAPE to provide longer-term protection to RPE cells and the underlying signal pathways involved. ARPE-19 cells were given CAPE pretreatment followed by t-BHP stimulation. We used in situ live cell staining with CellROX and MitoSOX to measure ROS accumulation; Annexin V-FITC/PI assay to evaluate cell apoptosis; ZO-1 immunostaining to observe tight junction integrity in the cells; RNA-seq to analyze changes in gene expression; q-PCR to validate the RNA-seq data; and Western Blot to examine MAPK signal pathway activation. CAPE significantly reduced both cellular and mitochondria ROS overproduction, restored the loss of ZO-1 expression, and inhibited apoptosis induced by t-BHP stimulation. We also demonstrated that CAPE reverses the overexpression of immediate early genes (IEGs) and activation of the p38-MAPK/CREB signal pathway. Either genetic or chemical deletion of UCP2 largely abolished the protective effects of CAPE. CAPE restrained ROS generation and preserved the tight junction structure of ARPE-19 cells against oxidative stress-induced apoptosis. These effects were mediated via UCP2 regulation of p38/MAPK-CREB-IEGs pathway.

Mechanism of Escherichia coli Lethality Caused by Overexpression of flhDC, the Flagellar Master Regulator Genes, as Revealed by Transcriptome Analysis.

The flhDC operon of Escherichia coli encodes a transcription factor that initiates flagella synthesis, elevates flagella construction and enhances cell motility, which all are energetically costly and highly regulated processes. In this study, we found that overexpression of flhDC genes from a strong regulatable pN15E6 plasmid could inhibit the growth of E. coli host cells and even eventually cause death. We used transcriptome analysis to investigate the mechanism of flhDC overexpression lethal to host bacteria. The results showed that a total of 568 differentially expressed genes (DEGs), including 378 up-regulated genes and 190 down-regulated genes were detected when the flhDC genes were over-expressed. Functional enrichment analysis results showed that the DEGs are related to a series of crucial biomolecular processes, including flagella synthesis, oxidative phosphorylation and pentose phosphate pathways, etc. We then examined, using RT-qPCR, the expression of key genes of the oxidative phosphorylation pathway at different time points after induction. Results showed that their expression increased in the early stage and decreased afterward, which was suggested to be the result of feedback on the overproduction of ROS, a strong side effect product of the elevated oxidative phosphorylation process. To further verify the level of ROS output, flhDC over-expressed bacteria cells were stained with DCHF-DA and a fluorescence signal was detected using flow cytometry. Results showed that the level of ROS output was higher in cells with over-expressed flhDC than in normal controls. Besides, we found upregulation of other genes (recN and zwf) that respond to ROS damage. This leads to the conclusion that the bacterial death led by the overexpression of flhDC genes is caused by damage from ROS overproduction, which leaked from the oxidative phosphorylation pathway.

A low-loss zero-index photonic crystal slab based on toroidal dipole mode.

Zero-index medium has profound application for light manipulation. Certain types of dielectric photonic crystals (PCs) may have zero effective index since they form Dirac cone at the Γ point of their band structure. Although zero index photonic crystals provide a solution to impedance mismatch in photonic integrated circuits, its propagation modes strongly radiate to the surrounding environment, which hampers their application for high-density integration. In this paper, by an appropriate design of PC's unit cell, toroidal dipole mode is excited at Dirac-point frequency through coupled Mie resonance to suppress radiative losses of other multipoles. The PCs with the Dirac-like dispersion at the Γ point can be mapped to an effective zero-index medium. The physical mechanism was utterly investigated by means of multipole decomposition and band structure analysis. Due to the non-radiation property of the toroidal dipole mode, the proposed photonic crystal slab process is low-loss based on numerical simulation. Moreover, its relatively simple design facilitates integration with future quantum photonic devices.

Glycoproteomic analysis reveals the effects of bisecting GlcNAc in intrahepatic cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (ICC) is the second major subtype of primary liver cancer and has caused more and more attention with increasing incidence and mortality worldwide. Our previous study found that bisecting N-glycans are commonly increased in ICC, while the effects and potential functions of bisecting GlcNAc in ICC are still largely unclear. In this study, we further confirmed that the structures of bisecting GlcNAc were significantly up-regulated in ICC compared with paracancer tissues by glycoproteomic data and lectin histochemistry. The expression of its glycosyltransferase MGAT3 was also up-regulated in ICC tissues at both mRNA and protein levels, and expression of MGAT3 is negatively correlated with overall survival explored by bioinformatic analyses and published datasets from 255 patients. Next, the silencing of MGAT3 could inhibit the growth and invasion of ICC cells, and overexpressing of MGAT3 only promoted ICC cell invasion. Further glycoproteomic analysis showed that the commonly glycoproteins modified by bisecting GlcNAc after MGAT3-overexpression in two ICC cell lines were mainly involved in cell movement-related biological processes, such as cell adhesion, integrin-related and ECM-receptor interaction. This study sheds light on the potential effects of bisecting GlcNAc in ICC cells and suggests that MGAT3 might be used as a potential target in the therapy of ICC.

SRY-related high-mobility-group box 4: Crucial regulators of the EMT in cancer.

The epithelial-mesenchymal transition (EMT) is a process of cell transformation under certain physiological and pathological states in which epithelial cells are transformed into mesenchymal cells with fibroblast-like properties, which confers upon them the increased invasion and migration capabilities of cancer cells. Previous studies have demonstrated that SRY-related high-mobility-group box 4 (Sox4) protein coordinates EMT-related pathways and EMT-related transcription factors, thereby regulating the EMT process. The focus of this review is to evaluate recent advances regarding the role of Sox4 protein in the cancer EMT. First, we provide an overview of the general background of Sox4 (structure and function) and the EMT in cancer. Next, we introduce the interactions between Sox4 protein and various factors during cancer EMT. Finally, we suggest directions for future investigations. In general, the information compiled in this paper should serve as a comprehensive repository of information on the subject matter and contribute to the design of other research and future efforts to develop therapeutic strategies that target the Sox4 protein.

Association of malnutrition with all-cause mortality in the elderly population: A 6-year cohort study.

BACKGROUND AND AIMS: Few studies have explored the association between malnutrition, defined by the Geriatric Nutritional Risk Index (GNRI), and all-cause mortality, particularly in the Chinese population. This study aimed to investigate the association between the GNRI and all-cause mortality in the elderly population. METHODS AND RESULTS: Participants aged ≥60 years were eligible for this study and were divided into three groups by the GNRI: An adequate nutrition group, participants with a GNRI ≥98; mild malnutrition group, participants with a GNRI ≥82 but <98; and a severe malnutrition group, participants with a GNRI <82. The results implied that there was a positive association between severe malnutrition and all-cause mortality in the total population (hazard ratio (HR): 2.591 and 95% confidence interval (CI): 1.729-3.884), male subjects (HR: 2.903 and 95% CI: 1.718-4.906), and female subjects (HR: 2.081 and 95% CI: 1.071-4.046). Similar associations between severe malnutrition and all-cause mortality were observed in both the 60-69 and 70-79 years age groups (HR: 2.863 and 2.600, 95% CI: 1.444-5.678 and 1.394-4.849, respectively). However, no significant association was observed between mild malnutrition and all-cause mortality. CONCLUSIONS: Severe malnutrition could increase all-cause mortality in the 60- to 79-year-old population. However, there was no association of mild malnutrition with all-cause mortality.

Effect of an arbuscular mycorrhizal fungus on maize growth and cadmium migration in a sand column.

The ecological role of arbuscular mycorrhizal fungi (AMF) on altering cadmium (Cd) migration in polluted soil is still unresolved. The present experiment aimed to clarify whether AMF can reduce Cd loss due to leaching at different Cd concentrations (0, 5, 10, and 15 mg L-1) with maize as a host plant cultured in a sand column. The effects of the arbuscular mycorrhizal fungus Funneliformis mosseae on the root morphology, exudate content, and Cd uptake by maize and Cd loss due to leaching were investigated. The AMF altered the root morphology and exudate content of the maize, resulting in increases in the root length, volume, surface area, tips and branch number and in the contents of soluble sugars, proteins, and amino acids in the root exudates, and the AMF increased maize biomass and Cd uptake by 22.0-31.0%. Moreover, the AMF significantly increased the contents of total and easily extractable glomalin-related soil protein (GRSP), increased Cd adsorption by sand particles and decreased the Cd concentration in the solution at a depth of 20 cm, resulting in a 67.5-97.2% decrease in the Cd loss due to leaching from the sand column. Furthermore, the root exudate content was very significantly positively correlated with Cd adsorption by the sand particles. Root length was significantly positively correlated with Cd uptake by the maize roots, but the average root diameter was very significantly negatively correlated with Cd uptake by maize. Thus, the AMF altered Cd migration by increasing the contents of GRSP and exudates and root morphology, which contributed to reducing the Cd concentration in the solution and Cd loss due to leaching from the sand column. Taken together, these results indicated that AMF serve an ecological function in reducing Cd loss due to leaching from polluted soil.

Risk stratification for prediction of locoregional recurrence in patients with pathologic T1-2N0 breast cancer after mastectomy.

BACKGROUND: Previous studies have revealed that nearly 15-20% of selected high-risk T1-2N0 breast cancers developed LRR after mastectomy. This study is aim to indentify the risk factors of locoregional recurrence (LRR) in patients with pathologic T1-2N0 breast cancer after mastectomy in a real-world and distinguish individuals who warrant postmastectomy radiotherapy (PMRT). METHODS: Female patients treated from 1999 to 2014 in National Cancer Center of China were retrospectively reviewed. A competing risk model was developed to estimate the cumulative incidence of LRR with death treated as a competing event. RESULTS: A total of 4841 patients were eligible. All underwent mastectomy plus axillary nodes dissection or sentinel node biopsy without PMRT. With a median follow-up of 56.4 months (range, 1-222 months), the 5-year LRR rate was 3.9%.Besides treatment era, age ≤ 40 years old (p < 0.001, hazard ratio [HR] = 2.262), tumor located in inner quadrant (p < 0.001, HR = 2.236), T2 stage (p = 0.020, HR = 1.419), and negative expressions of estrogen receptor (ER) and progesterone receptor (PR) (p = 0.032, HR = 1.485), were patients-related independent risk factors for LRR. The 5-year LRR rates were 1.7, 3.5, and 15.0% for patients with zero, 1-2, and 3-4 risk factors (p < 0.001). CONCLUSIONS: Risk Stratification based on age, T stage, ER/PR status and tumor location can stratify patients with pT1-2 N0 breast cancer into subgroups with different risk of LRR. PMRT might be suggested for patients with 3-4 risk factors.

Hypofractionated versus conventional fractionated postmastectomy radiotherapy for patients with high-risk breast cancer: a randomised, non-inferiority, open-label, phase 3 trial.

BACKGROUND: To our knowledge, no randomised study has compared postmastectomy hypofractionated radiotherapy with conventional fractionated radiotherapy in patients with breast cancer. This study aimed to determine whether a 3-week schedule of postmastectomy hypofractionated radiotherapy is as efficacious and safe as a 5-week schedule of conventional fractionated radiotherapy. METHODS: This randomised, non-inferiority, open-label, phase 3 study was done in a single academic hospital in China. Patients aged 18-75 years who had undergone mastectomy and had at least four positive axillary lymph nodes or primary tumour stage T3-4 disease were eligible to participate. Patients were randomly assigned (1:1) according to a computer-generated central randomisation schedule, without stratification, to receive chest wall and nodal irradiation at a dose of 50 Gy in 25 fractions over 5 weeks (conventional fractionated radiotherapy) or 43·5 Gy in 15 fractions over 3 weeks (hypofractionated radiotherapy). The modified intention-to-treat population (including all eligible patients who underwent randomisation but excluding those who were considered ineligible or withdrew consent after randomisation) was used in primary and safety analyses. The primary endpoint was 5-year locoregional recurrence, and a 5% margin was used to establish non-inferiority (equivalent to a hazard ratio <1·883). This trial is registered at ClinicalTrials.gov, number NCT00793962. FINDINGS: Between June 12, 2008, and June 16, 2016, 820 patients were enrolled and randomly assigned to the conventional fractionated radiotherapy group (n=414) or hypofractionated radiotherapy group (n=406). 409 participants in the conventional fractionated radiotherapy group and 401 participants in the hypofractionated radiotherapy group were included in the modified intention-to-treat analyses. At a median follow-up of 58·5 months (IQR 39·2-81·8), 60 (7%) patients had developed locoregional recurrence (31 patients in the hypofractionated radiotherapy group and 29 in the conventional fractionated radiotherapy group); the 5-year cumulative incidence of locoregional recurrence was 8·3% (90% CI 5·8-10·7) in the hypofractionated radiotherapy group and 8·1% (90% CI 5·4-10·6) in the conventional fractionated radiotherapy group (absolute difference 0·2%, 90% CI -3·0 to 2·6; hazard ratio 1·10, 90% CI 0·72 to 1·69; p<0·0001 for non-inferiority). There were no significant differences between the groups in acute and late toxicities, except that fewer patients in the hypofractionated radiotherapy group had grade 3 acute skin toxicity than in the conventional fractionated radiotherapy group (14 [3%] of 401 patients vs 32 [8%] of 409 patients; p<0·0001). INTERPRETATION: Postmastectomy hypofractionated radiotherapy was non-inferior to and had similar toxicities to conventional fractionated radiotherapy in patients with high-risk breast cancer. Hypofractionated radiotherapy could provide more convenient treatment and allow providers to treat more patients. FUNDING: National Key Projects of Research and Development of China; the Chinese Academy of Medical Science Innovation Fund for Medical Sciences; and Beijing Marathon of Hope, Cancer Foundation of China.

LncRNA and mRNA signatures associated with neoadjuvant chemoradiotherapy downstaging effects in rectal cancer.

Radiotherapy plays a crucial role in combined treatment modality in local advanced rectal cancer (LARC). While neoadjuvant chemoradiotherapy responses were variable in LARC patients, so, it is important to identify genes that closely associated with short-term and long-term responses to radiotherapy. In this study, we profiled long noncoding RNAs (lncRNAs) and messenger RNAs (mRNAs) expression values of LARC patients with different neoadjuvant chemoradiotherapy downstaging depth score based on Agilent Arraystar Human LncRNA V3.0 Array(Agilent, CA). LncRNAs and mRNAs with aberrant expression values between the two groups of LARC patients were identified and lncRNA-miRNA-mRNA regulation network was also obtained through the combination of miRcode and miRTarBase database. Gene interaction network and module analysis of differential expression mRNAs contained in the lncRNA-miRNA-mRNA network identified five hub genes, including KRAS, PDPK1, PPP2R5C, PPP2R1B, and YES1, that should be closely associated with LARC's response to chemoradiotherapy. Besides, Kaplan-Meier analysis based on the Cyber Research Center (CRC) data set from The Cancer Genome Atlas indicated that aberrant expression of the five hub genes is significantly associated with CRC overall survival. In conclusion, we obtained several biomarkers that should be associated with neoadjuvant chemoradiotherapy response in LARC, which should be helpful for individual treatment and prognosis improvement.

Mechanisms explaining the efficacy of psoralidin in cancer and osteoporosis, a review.

Psoralidin (PSO) is a natural phenolic coumarin that is extracted from the seeds of Psoralea corylifolia L. PSO possesses a variety of pharmacological activities, including anti-oxidative, antibacterial, anti-inflammatory, anti-depressive and estrogenic-like effects. Other studies have indicated that PSO plays a beneficial role in multiple disease, especially cancer and osteoporosis. In this review, we first outline the basic background of PSO. Then we introduced the molecular mechanisms and signaling pathways of PSO in multiple cancers to elucidate its anticancer potential via inducing oxidative stress and apoptosis, inhibiting proliferation, promoting autophagy-dependent cell death, and activating the estrogen receptors (ER)-signaling pathway. Finally, we recommend the direction of future investigations. In general, the information compiled in this paper should serve as a comprehensive repository of information to help design PSO in other research and future efforts.

Down-staging depth score to predict outcomes in locally advanced rectal cancer achieving ypI stage after neoadjuvant chemo-radiotherapy versus de novo stage pI cohort: A propensity score-matched analysis.

OBJECTIVE: Prognosis of patients with locally advanced rectal cancer (LARC) but achieving ypT1-2N0 stage after neoadjuvant concurrent chemo-radiotherapy (CRT) has been shown to be favorable. This study aims to determine whether the long-term outcome of ypT1-2N0 cases can be comparable to that of pT1-2N0 cohort that received definitive surgery for early disease. METHOD: From January 2008 to December 2013, 449 consecutive patients with rectal cancer were treated and their outcome maintained in a database. Patients with LARC underwent total mesorectal excision (TME) surgery at 4-8 weeks after completion of CRT, and those achieving stage ypI were identified as a group. As a comparison, stage pI group pertains to patients whose initially limited disease was not upstaged after TME surgery alone. After propensity score matching (PSM), comparisons of local regional control (LC), distant metastasis-free survival (DMFS), disease-free survival (DFS) and overall survival (OS) were performed using Kaplan-Meier analysis and log-rank test between ypI and pI groups. Down-staging depth score (DDS), a novel method of evaluating CRT response, was used for subset analysis. RESULTS: Of the 449 patients, 168 matched cases were generated for analysis. Five-year LC, DMFS, DFS and OS for stage pI vs. ypI groups were 96.7% vs. 96.4% (P=0.796), 92.7% vs. 73.6% (P=0.025), 91.2% vs. 73.6% (P=0.080) and 93.1% vs. 72.3% (P=0.040), respectively. In the DDS-favorable subset of the ypI group, LC, DMFS, DFS and OS resulted in no significant differences in comparison with the pI group (P=0.384, 0.368, 0.277 and 0.458, respectively). CONCLUSIONS: LC was comparable in both groups; however, distant metastasis developed more frequently in down-staged LARC than de novo early stage cases, reflecting the need to improve the efficacy of systemic treatment despite excellent pathologic response. DDS can be an indicator to identify a subset of the ypI group whose long-term oncologic outcomes are as good as those of stage pI cohort.

Patients with pathological stage N2 rectal cancer treated with early adjuvant chemotherapy have a lower treatment failure rate.

BACKGROUND: In this era of oxaliplatin-based adjuvant therapy, the optimal sequence in which chemoradiotherapy should be administered for pathological stage N2 rectal cancer is unknown. The aim of this study was to investigate this sequence. METHODS: In the primary adjuvant concurrent chemoradiotherapy (A-CRT) group (n = 71), postoperative concurrent chemoradiotherapy was administered before adjuvant chemotherapy. In the primary adjuvant chemotherapy (A-CT) group (n = 43), postoperative concurrent chemoradiotherapy was administered during or after adjuvant chemotherapy. Postoperative radiotherapy comprised 45-50.4 Gy in 25-28 fractions. Concurrent chemotherapy comprised two cycles of oral capecitabine (1,600 mg/m2) on days 1-14 and 22-35. Patients receiving adjuvant chemotherapy with four or more cycles of XELOX (oxaliplatin plus capecitabine) or eight or more cycles of FOLFOX (fluorouracil, leucovorin, and oxaliplatin) were included. RESULTS: Between June 2005 and December 2013, data for 114 qualified rectal cancer patients were analyzed. The percentages of patients in whom treatment failed in the A-CRT and A-CT groups were 33.8% and 16.3%, respectively (p = 0.042). More patients had distant metastases in the A-CRT group than in the A-CT group (32.4% vs. 14.3%, p = 0.028). Multivariate analysis indicated that the sequence in which chemoradiotherapy was administered (A-CT vs. A-CRT) was an independent prognostic factor for both estimated disease-free survival [hazard ratio (HR) 0.345, 95% confidence interval (CI) 0.137-0.868, p = 0.024] and estimated distant metastasis-free survival (HR 0.366, 95% CI 0.143-0.938, p = 0.036). CONCLUSIONS: In pathological stage N2 rectal cancer patients, administering adjuvant chemotherapy before chemoradiotherapy led to a lower rate of treatment failure, especially with respect to distant metastasis. Adjuvant chemotherapy prescribed as early as possible might benefit this cohort of patients in this era of oxaliplatin-based adjuvant therapy.

Sulfur-Doped Carbon Nitride Polymers for Photocatalytic Degradation of Organic Pollutant and Reduction of Cr(VI).

As a promising conjugated polymer, binary carbon nitride has attracted extensive attention as a metal-free and visible-light-responsive photocatalyst in the area of photon-involving purification of water and air. Herein, we report sulfur-doped polymeric carbon nitride microrods that are synthesized through thermal polymerization based on trithiocyanuric acid and melamine (TM) supramolecular aggregates. By tuning the polymerization temperature, a series of sulfur-doped carbon nitride microrods are prepared. The degradation of Rhodamine B (RhB) and the reduction of hexavalent chromium Cr(VI) are selected as probe reactions to evaluate the photocatalytic activities. Results show that increasing pyrolysis temperature leads to a large specific surface area, strong visible-light absorption, and accelerated electron-hole separation. Compared to bulk carbon nitride, the highly porous sulfur-doped carbon nitride microrods fabricated at 650 °C exhibit remarkably higher photocatalytic activity for degradation of RhB and reduction of Cr(VI). This work highlights the importance of self-assembly approach and temperature-control strategy in the synthesis of photoactive materials for environmental remediation.

Survival benefit with IMRT following narrow-margin hepatectomy in patients with hepatocellular carcinoma close to major vessels.

BACKGROUND & AIMS: To investigate the role of post-operative intensity-modulated radiotherapy (IMRT) in patients receiving narrow-margin hepatectomy for hepatocellular carcinoma (HCC) located close to the major vessels. METHODS: This exploratory study involved 181 HCC patients. Of them, 116 were treated with narrow-margin (<1.0 cm) hepatectomy. Thirty-three of the 116 underwent postoperative IMRT (Group A), while 83 did not receive radiotherapy (Group B). The remaining 65 patients underwent wide-margin (≥1.0 cm) hepatectomy (Group C). Prognosis and patterns of recurrence were assessed in the three groups. RESULTS: The 3-year overall survival (OS) and disease-free survival (DFS) rates were 89.1 and 64.2% in Group A, 67.7 and 52.2% in Group B and 86.0 and 60.1% in Group C respectively. The OS and DFS of Group A and Group C patients surpassed those of Group B patients (Group A vs. B, P = 0.009 and P = 0.038; and Group C vs. B, P = 0.002 and P = 0.010). Patients in Groups A and C experienced significantly fewer early recurrences than did patients in Group B (P = 0.002). Furthermore, patients in Groups A and C experienced substantially fewer intrahepatic marginal (P = 0.048) and diffuse recurrences (P = 0.018) and extrahepatic metastases (P = 0.038) than did patients in Group B. No patient developed radiation-induced liver disease. CONCLUSIONS: Post-operative IMRT following narrow-margin hepatectomy may be a favourable therapy for both its safety profile and clinical benefit in patients with HCC located close to the major vessels.