Node-sparing modified short-course Radiotherapy Combined with CAPOX and Tislelizumab for locally Advanced MSS of Middle and low rectal Cancer (mRCAT): an open-label, single-arm, prospective, multicentre clinical trial.

BACKGROUND: Neoadjuvant chemoradiotherapy followed by total mesorectal excision is a standard treatment for locally advanced rectal cancer. Mismatch repair-deficient locally advanced rectal cancer (LARC) was highly sensitive to PD-1 blockade. However, most rectal cancers are microsatellite stable (MSS) or mismatch repair-proficient (pMMR) subtypes for which PD-1 blockade is ineffective. Radiation can trigger the activation of CD8 + T cells, further enhancing the responses of MSS/pMMR rectal cancer to PD-1 blockade. Radioimmunotherapy offers a promising therapeutic modality for rectal cancer. Progenitor T exhausted cells are abundant in tumour-draining lymph nodes and play an important role in immunotherapy. Conventional irradiation fields include the mesorectum and regional lymph nodes, which might cause considerable damage to T lymphocytes and radiation-induced fibrosis, ultimately leading to a poor response to immunotherapy and rectal fibrosis. This study investigated whether node-sparing modified short-course irradiation combined with chemotherapy and PD-1 blockade could be effective in patients with MSS/ pMMR LARC. METHODS: This was a open-label, single-arm, multicentre, prospective phase II trial. 32 LARC patients with MSS/pMMR will receive node-sparing modified short-course radiotherapy (the irradiated planned target volume only included the primary tumour bed but not the tumour-draining lymph nodes, 25 Gy/5f, 5 Gy/f) followed by CAPOX and tislelizumab. CAPOX and tislelizumab will be started two days after the completion of radiotherapy: oxaliplatin 130 mg/m2 intravenous infusion, day 1; capecitabine 1000 mg/m2 oral administration, days 1-14; and tislelizumab 200 mg, intravenous infusion, day 1. There will be four 21-day cycles. TME will be performed at weeks 14-15. We will collect blood, tumour, and lymphoid specimens; perform flow cytometry and in situ multiplexed immunofluorescence detection; and analyse the changes in various lymphocyte subsets. The primary endpoint is the rate of pathological complete response. The organ preservation rate, tumour regression grade, local recurrence rate, disease-free survival, overall survival, adverse effects, and quality of life will also be analysed. DISCUSSION: In our research, node-sparing modified radiotherapy combined with immunotherapy probably increased the responsiveness of immunotherapy for MSS/pMMR rectal cancer patients, reduced the occurrence of postoperative rectal fibrosis, and improved survival and quality of life. This is the first clinical trial to utilize a node-sparing radiation strategy combined with chemotherapy and PD-1 blockade in the neoadjuvant treatment of rectal cancer, which may result in a breakthrough in the treatment of MSS/pMMR rectal cancer. TRIAL REGISTRATION: This study was registered at www. CLINICALTRIALS: gov . TRIAL REGISTRATION NUMBER: NCT05972655. Date of registration: 31 July 2023.

Relationship Between Microstructural Alterations and Cognitive Decline After Whole-Brain Radiation Therapy for Brain Metastases: An Exploratory Whole-Brain MR Analysis Based on Neurite Orientation Dispersion and Density Imaging.

BACKGROUND: Cognitive impairment frequently occurs in patients with brain metastases (BM) after whole-brain radiotherapy (WBRT). It is crucial to explore the underlying mechanisms of cognitive impairment in BM patients receiving WBRT. PURPOSE: To detect brain microstructural alterations in patients after WBRT by neurite orientation dispersion and density imaging (NODDI), and evaluate the performance of microstructural alterations in predicting cognitive impairment. STUDY TYPE: Prospective. POPULATION: Twenty-six patients (seven female; mean age, 60.9 years). FIELD STRENGTH/SEQUENCE: 3-T, multi-shell diffusion-weighted single-shot echo-planar sequence. Three-dimensional magnetization-prepared rapid acquisition with gradient echo sequence. ASSESSMENT: Mini-mental state examination (MMSE) evaluations were conducted prior to, following, 1 and 3 months after WBRT. The diffusion data were collected twice, 1 week before and 1 week after WBRT. NODDI analysis was conducted to assess microstructural alterations in whole brain (orientation dispersion index, neurite density index, volume fraction of isotropic water molecules). Reliable change indices (RCI) of MMSE were used to measure cognitive decline. The performance of support vector machine models based on NODDI parameters and clinical features (prednisone usage, tumor volume, etc.) in predicting MMSE-RCI was evaluated. STATISTICAL TESTS: Paired t-test to assess alterations of NODDI measures and MMSE during follow-up. Statistical significance level of P-value <0.05. RESULTS: Significantly decreased MMSE score was found at 3 months after WBRT. After WBRT, corpus callosum, medial prefrontal cortex, limbic lobe, occipital lobe, parietal lobe, putamen, globus pallidus lentiform, and thalamus demonstrated damage in NODDI parameters. The predicted MMSE-RCI based on NODDI features was significantly associated with the measured MMSE-RCI at 1 month (R = 0.573; P = 0.003) and 3 months (R = 0.687; P < 0.0001) after WBRT. DATA CONCLUSION: Microstructural alterations in several brain regions including the middle prefrontal and limbic cortexes were observed in patients with BM following WBRT, which may contribute to subsequent cognitive decline. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

SMYD2 regulates vascular smooth muscle cell phenotypic switching and intimal hyperplasia via interaction with myocardin.

The SET and MYND domain-containing protein 2 (SMYD2) is a histone lysine methyltransferase that has been reported to regulate carcinogenesis and inflammation. However, its role in vascular smooth muscle cell (VSMC) homeostasis and vascular diseases has not been determined. Here, we investigated the role of SMYD2 in VSMC phenotypic modulation and vascular intimal hyperplasia and elucidated the underlying mechanism. We observed that SMYD2 expression was downregulated in injured carotid arteries in mice and phenotypically modulated VSMCs in vitro. Using an SMC-specific SMYD2 knockout mouse model, we found that SMYD2 ablation in VSMCs exacerbated neointima formation after vascular injury in vivo. Conversely, SMYD2 overexpression inhibited VSMC proliferation and migration in vitro and attenuated arterial narrowing in injured vessels in mice. SMYD2 downregulation promoted VSMC phenotypic switching accompanied with enhanced proliferation and migration. Mechanistically, genome-wide transcriptome analysis and loss/gain-of-function studies revealed that SMYD2 up-regulated VSMC contractile gene expression and suppressed VSMC proliferation and migration, in part, by promoting expression and transactivation of the master transcription cofactor myocardin. In addition, myocardin directly interacted with SMYD2, thereby facilitating SMYD2 recruitment to the CArG regions of SMC contractile gene promoters and leading to an open chromatin status around SMC contractile gene promoters via SMYD2-mediated H3K4 methylation. Hence, we conclude that SMYD2 is a novel regulator of VSMC contractile phenotype and intimal hyperplasia via a myocardin-dependent epigenetic regulatory mechanism.

Reduced radiation dose and volume of contrast medium in heart rate-based, one-stop computed tomography angiography of coronary, carotid and cerebrovascular arteries.

BACKGROUND: Computed tomography angiography (CTA) is a reliable, non-invasive screening method for diagnosing panvascular disease. By using low contrast agent volume, CTA imaging enables one-stop multi-organ scanning, thereby minimizing the potential risk of contrast-induced nephropathy in patients with impaired renal function. PURPOSE: To evaluate the feasibility of one-stop CTA following a heart rate (HR)-based protocol using a low volume of contrast medium (CM) for examination of the coronary, carotid and cerebrovascular arteries. MATERIAL AND METHODS: Sixty patients undergoing coronary carotid, and cerebrovascular CTA after a single injection of CM were recruited and randomly divided into two groups. Group A (n = 30) underwent CTA following a traditional protocol. The timing of the scans in Group B (n = 30) was determined according to the patient's HR. RESULTS: The CT values for the thoracic aorta (432.2 ± 104.28 HU), anterior cerebral artery (303.96 ± 99.29 HU), and right coronary artery (366.70 ± 85.10 HU) in Group A did not differ significantly from those in Group B (445.80 ± 106.13, 293.73 ± 75.25 and 344.13 ± 111.04 HU, respectively). The qualities of most of the scanned images for both groups were scored as 3 or 4 (on a five-point scale). The radiation dose and the volume of CM were significantly higher in Group A (303.05 ± 110.95 mGy) (100 mL) than in Group B (239.46 ± 101.12 mGy) (50 mL). CONCLUSION: The radiation dose and volume of CM were significantly reduced in CTA following the HR-based protocol. The personalized administration of CM also simplified the scanning process.

Cardiac-Specific Suppression of Valosin-Containing Protein Induces Progressive Heart Failure and Premature Mortality Correlating with Temporal Dysregulations in mTOR Complex 2 and Protein Phosphatase 1.

Valosin-containing protein (VCP), an ATPase-associated protein, is emerging as a crucial regulator in cardiac pathologies. However, the pivotal role of VCP in the heart under physiological conditions remains undetermined. In this study, we tested a hypothesis that sufficient VCP expression is required for cardiac development and physiological cardiac function. Thus, we generated a cardiac-specific VCP knockout (KO) mouse model and assessed the consequences of VCP suppression on the heart through physiological and molecular studies at baseline. Our results reveal that homozygous KO mice are embryonically lethal, whereas heterozygous KO mice with a reduction in VCP by ~40% in the heart are viable at birth but progressively develop heart failure and succumb to mortality at the age of 10 to 12 months. The suppression of VCP induced a selective activation of the mammalian target of rapamycin complex 1 (mTORC1) but not mTORC2 at the early age of 12 weeks. The prolonged suppression of VCP increased the expression (by ~2 folds) and nuclear translocation (by >4 folds) of protein phosphatase 1 (PP1), a key mediator of protein dephosphorylation, accompanied by a remarked reduction (~80%) in AKTSer473 phosphorylation in VCP KO mouse hearts at a later age but not the early stage. These temporal molecular alterations were highly associated with the progressive decline in cardiac function. Overall, our findings shed light on the essential role of VCP in the heart under physiological conditions, providing new insights into molecular mechanisms in the development of heart failure.

Microplastics-biofilm in aquatic ecosystem: Formation, pollutants complexation, greenhouse gas emission and ecotoxicology.

The omnipresent microplastics (MPs) have gradually become a significant environmental problem due to its adverse consequences for ecological systems. MPs serve as substrates for biofilms colonization, which enhances adsorption of harmful contaminants on MPs surface in the aquatic ecosystem. The present study provides a critical discussion on the mechanism involved in MPs-biofilm formation, microbial colonization and the robust factors influencing the process in the aquatic ecosystem. Subsequently, the impact of MPs-biofilm on adsorption of inorganic and organic contaminants is explored. The ecological significance of MPs-biofilm associated pollutant complex for promoting greenhouse gases (GHGs) emissions from aquatic ecosystem is extensively discussed for understanding the climatic risk. Furthermore, the discussion is extended over ecotoxicological impact of MPs-biofilm on aquatic biodiversity and humans. The protective extracellular polymeric substances secreted by colonised bacteria over MPs during biofilm formation creates sticky MPs surface for heteroaggregates formation with swift adsorption of chemical compounds and microorganisms. MPs with functional aromatic groups facilitate the bacterial adhesion on the surface, but affect formation of biofilm. Alternatively, MPs-biofilm promotes the Mn and Fe hydrous oxides formation that can co-precipitate with heavy metal ions and facilitate in remediation measures. However, MPs biodegradation generates GHGs emission per unit mass, comparably more from freshwater than marine ecosystem. Considering the toxicity, MPs-biofilm induces the oxidative response in fishes, causing painful death and thus, destroys aquatic biodiversity. This study will be useful to address MPs-biofilm associated pollution scenario via trace, test and treat strategy involving future engineering research framework for ecological restoration.

Mapping of quantitative trait loci for leaf rust resistance in the wheat population 'Xinmai 26/Zhoumai 22'.

Leaf rust, caused by the fungal pathogen Puccinia triticina (Pt), is one of the major and dangerous diseases of wheat, and has caused serious yield loss of wheat worldwide. Here, we investigated adult-plant resistance (APR) to leaf rust in a recombinant inbred line (RIL) population derived from 'Xinmai 26' and 'Zhoumai 22' over 3 years. Linkage mapping for APR to leaf rust revealed four quantitative trait loci (QTL) in this RIL population. Two QTL, QLr.hnau-2BS and QLr.hnau-3BS were contributed by 'Zhoumai22', whereas QLr.hnau-2DS and QLr.hnau-5AL were contributed by 'Xinmai 26'. The QLr.hnau-2BS covering a race-specific resistance gene Lr13 showed the most stable APR to leaf rust. Overexpression of Lr13 significantly increased APR to leaf rust. Interestingly, we found that a CNL(coiled coil-nucleotide-binding site-leucine-rich repeat)-like gene, TaCN, in QLr.hnau-2BS completely co-segregated with leaf rust resistance. The resistant haplotype TaCN-R possessed half the sequence of the coiled-coil domain of TaCN protein. Lr13 strongly interacted with TaCN-R, but did not interact with the full-length TaCN (TaCN-S). In addition, TaCN-R was significantly induced after Pt inoculation and changed the sub-cellular localization of Lr13 after interaction. Therefore, we hypothesized that TaCN-R mediated leaf rust resistance possibly by interacting with Lr13. This study provides important QTL for APR to leaf rust, and new insights into understanding how a CNL gene modulates disease resistance in common wheat.

Mapping QTL conferring flag leaf senescence in durum wheat cultivars.

Flag leaf senescence is a critical factor affecting the yield and quality of wheat. The aim of this study was to identify QTLs associated with flag leaf senescence in an F10 recombinant inbred line population derived from durum wheats UC1113 and Kofa. Bulked segregant analysis using the wheat 660K SNP array identified 3225 SNPs between extreme-phenotype bulks, and the differential SNPs were mainly clustered on chromosomes 1A, 1B, 3B, 5A, 5B, and 7A. BSR-Seq indicated that the significant SNPs were mainly located in two intervals of 354.0-389.0 Mb and 8.0-15.0 Mb on 1B and 3B, respectively. Based on the distribution of significant SNPs on chromosomes 1B and 3B, a total of 109 insertion/deletion (InDel) markers were developed, and 8 of them were finally used to map QTL in UC1113/Kofa population for flag leaf senescence. Inclusive composite interval mapping identified two major QTL in marker intervals Mar2005-Mar2116 and Mar207-Mar289, explaining 14.2-15.4% and 31.4-68.6% of the phenotypic variances across environments, respectively. Using BSR-Seq, gene expression and sequence analysis, the TraesCS1B02G211600 and TraesCS3B02G023000 were identified as candidate senescence-associated genes. This study has potential to be used in cloning key genes for flag leaf senescence and provides available molecular markers for genotyping and marker-assisted selection breeding. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-023-01410-3.

Coulometric method with titratable impurity analysis and mass balance method: convert acidimetric purity to chemical purity for SI-traceable highest standard of qNMR (potassium hydrogen phthalate), and verified by qNMR.

In this study, the coulometric method with titratable impurity analysis and the mass balance method were successfully applied in the quantification of the certified reference material of potassium hydrogen phthalate (KHP) with accurate metrological traceability of chemical purity value (99.983% with an expanded uncertainty of 0.024%, k = 2). In contrast to the general coulometric titration method, the coulometric method with titratable impurity analysis enables the conversion of acidimetric purity to chemical purity: The acidimetric purity was determined by coulometric titration method, and then the impurities that may be titrated as principal components were found as far as possible using various methods and the result of deducting these impurities from the acidimetric purity can be considered as chemical purity. The mass balance method also accounted for all possible types of impurities as much as possible to improve the accuracy of the determined result. The accuracy and reliability of the purity results were subsequently verified by a two-step quantitative nuclear magnetic resonance (qNMR) method. This KHP certified reference material was the first hydrophilic internal standard of qNMR (applied in polar solvents) with an expanded uncertainty lower than 0.03%, which will become a major reference standard in the organic chemistry traceable calibration chain, especially when evaluating hydrophilic organic compounds to obtain purity values with very low uncertainty.

Topical diquafosol versus hyaluronic acid for the treatment of dry eye disease: a meta-analysis of randomized controlled trials.

BACKGROUND: Diquafosol enhances fluid transfer and mucin secretion on ocular surface, which has been suggested as an effective treatment for dry eye disease (DED). The aim of the systematic review and meta-analysis was to compare the efficacy and safety of topical diquafosol versus hyaluronic acid (HA) for DED. METHODS: Relevant randomized controlled trials were obtained via search of electronic including PubMed, Embase, Cochrane Library, and Web of Science. A random-effects model was used to pool the results after incorporating the influence of potential heterogeneity. RESULTS: A total of nine RCTs involving 1295 patients with DED were included in the meta-analysis. Compared to treatment with 0.1% HA, topical treatment with 3% diquafosol significantly improved the Ocular Surface Disease Index (mean difference (MD): - 3.59, 95% confidence interval (CI): - 4.68 to - 2.50, p < 0.001; I2 = 6%), results of Schirmer's test (MD: 1.08 mm, 95% CI: 0.41 to 1.76, p = 0.002; I2 = 0%), tear breakup time (MD: 0.60 s, 95% CI: 0.20 to 0.99, p = 0.003; I2 = 63%), corneal fluorescein staining score (MD: - 0.20, 95% CI: - 0.37 to - 0.03, p = 0.02; I2 = 58%), and ocular rose bengal staining score (MD: - 0.62, 95% CI: - 0.88 to - 0.35, p < 0.001; I2 = 15%). No severe adverse events were reported. Topical use of diquafosol was associated with a higher risk of overall adverse events as compared to HA (odds ratio: 1.71, 95% CI: 1.08 to 2.71, p = 0.02; I2 = 18%). CONCLUSIONS: Topical treatment with 3% diquafosol may be more effective than 0.1% HA for patients with DED. However, the long-term efficacy and tolerability of diquafosol still need to be determined.

Validity and reliability of the Chinese version of the Health Literacy Scale Short-Form in the Chinese population.

BACKGROUND: Health literacy is closely related to health status. Measuring public health literacy levels helps to warn of health status and manage health problems through timely interventions. The items of relevant evaluation tools are complex and numerous in China, and there is no recognized health literacy brief scale for the whole population. To translate the 12-item short-form health literacy scale (HLS-SF12) and test the validity and reliability of the Chinese version of the HLS-SF12 in the Chinese population. METHODS: The HLS-SF12 was translated into Chinese using the procedures of translation, back translation, and cultural debugging. 10,951 residents were selected by quota sampling method to test the validity and reliability of the scale, and 33 people were selected to retest after 2 weeks. The reliability was tested by using internal consistency coefficient and test-retest reliability. The validity was tested by using confirmatory factor analysis, content validity, convergent validity and discriminant validity. RESULTS: The Cronbach's Alpha coefficient for the total scale was 0.94, and the test-retest reliability was 0.89. The Cronbach's Alpha coefficients for the three subscales of health care, disease prevention, and health promotion respectively were 0.86, 0.86, 0.87, and the test-retest reliability respectively were 0.91, 0.79, 0.63. The confirmatory factor analysis identified a three factors model and showed nice goodness of fit indices for Chinese HLS-SF12 (GFI = 0.96, CFI = 0.97, IFI = 0.97, TLI = 0.96, and RMSEA = 0.07). CONCLUSION: The Chinese version of the HLS-SF12 has good reliability and validity, and can be used as a tool to evaluate the health literacy of Chinese people.

A cell wall invertase modulates resistance to fusarium crown rot and sharp eyespot in common wheat.

Fusarium crown rot (FCR) and sharp eyespot (SE) are serious soil-borne diseases in wheat and its relatives that have been reported to cause wheat yield losses in many areas. In this study, the expression of a cell wall invertase gene, TaCWI-B1, was identified to be associated with FCR resistance through a combination of bulk segregant RNA sequencing and genome resequencing in a recombinant inbred line population. Two bi-parental populations were developed to further verify TaCWI-B1 association with FCR resistance. Overexpression lines and ethyl methanesulfonate (EMS) mutants revealed TaCWI-B1 positively regulating FCR resistance. Determination of cell wall thickness and components showed that the TaCWI-B1-overexpression lines exhibited considerably increased thickness and pectin and cellulose contents. Furthermore, we found that TaCWI-B1 directly interacted with an alpha-galactosidase (TaGAL). EMS mutants showed that TaGAL negatively modulated FCR resistance. The expression of TaGAL is negatively correlated with TaCWI-B1 levels, thus may reduce mannan degradation in the cell wall, consequently leading to thickening of the cell wall. Additionally, TaCWI-B1-overexpression lines and TaGAL mutants showed higher resistance to SE; however, TaCWI-B1 mutants were more susceptible to SE than controls. This study provides insights into a FCR and SE resistance gene to combat soil-borne diseases in common wheat.

Resveratrol attenuated high intensity exercise training-induced inflammation and ferroptosis via Nrf2/FTH1/GPX4 pathway in intestine of mice.

BACKGROUND: Moderate exercise has beneficial effects for human health and is helpful for the protection against several diseases. However, high intensity exercise training caused gastrointestinal syndrome. Resveratrol, a plant extract, plays a vital role in protecting various organs. However, whether resveratrol protected mice against high intensity exercise training-induced intestinal damage remains unclear. In this study, our objective was to investigate the protective effects and mechanism of resveratrol in high intensity exercise training-treated mice. METHODS: Mice were treated with swimming exercise protocol and/or resveratrol (15 mg/kg/day) for 28 consecutive days. Then, the mice were sacrificed, and a series of evaluation indicators, including inflammatory factors and intestinal permeability of the gut, were measured based on this model. The expressions of inflammatory factors (tumor necrosis factor (TNF)-α; interferon (IFN)-γ, interleukin (IL)-6 and IL-10), oxidative stress (Nrf2, glutathione (GSH), hydrogen peroxide (H2 O2), catalase (CAT) and malondialdehyde(MDA)), intestinal barrier (gut permeability, ZO-1, Occludin and Claudin-1 as well as ferroptosis (Fe2+, Fe3+, SLC7A11, glutathioneperoxidase 4 (GPX4) and ferritin heavy chain 1 (FTH1)) were measured, respectively. RESULTS: High intensity exercise training induced colon damage, manifested as inflammation (increased TNF-α, IFN-γ and IL-6 concentrations, and decreased IL-10 concentration), oxidative stress (the increase of H2O2 and MDA concentration, and the reduced CAT and GSH activities), intestinal barrier injury (increased gut permeability and intestinal fatty-acid binding protein concentration,and inhibited ZO-1, Occludin and Claudin-1 expressions) and ferroptosis (the increased of Fe2+ and Fe3+ concentrations, and suppressed phosphorylated Nrf2, SLC7A11, GPX4 and FTH1), which was relieved by resveratrol treatment in mice. DISCUSSION: Resveratrol attenuated high intensity exercise training-induced inflammation and ferroptosis through activating Nrf2/ FTH1/GPX4 pathway in mouse colon, which providing new ideas for the prevention and treatment of occupational disease in athlete.

SI-traceable purity assignment of volatile material ethylbenzene by quantitative nuclear magnetic resonance spectroscopy.

In this study, a quantitative nuclear magnetic resonance (qNMR) method was developed to assign the SI-traceable purity of ethylbenzene, a volatile material, which is a colorless flammable liquid hydrocarbon at room temperature. An ethanol certified reference material having a similar boiling point was used as an internal standard to avoid measurement error arising from the volatilization of ethylbenzene. The reference value of the ethylbenzene study material was obtained by the mass balance method by subtracting all the impurities including water, inorganic impurities, and structurally related impurities (e.g. acetophenone, benzene, isobutylbenzene, sec-butylbenzene, methylcyclohexane), which is regarded as the traditional approach for purity assignment for organic compounds. The results of qNMR showed that the purity of the ethylbenzene study material was 998.6 ± 3.8 mg/g at a 95% confidence interval, which was consistent with the reference value of 998.9 ± 1.3 mg/g.

Spectroscopic evidence of S∴N and S∴O hemibonds in heterodimer cations.

Computational and condensed phase experimental evidence for the existence of S∴N and S∴O hemibonded structures has been reported previously, but no gas phase experimental evidence has been reported. To experimentally explore the existence of the S∴N and S∴O hemibonds in the gas phase, we recorded the infrared photodissociation action spectra of four cationic clusters: [CH3SH-NH3]+, [CH3SCH3-NH3]+, [CH3SCH3-H2O]+, and [CH3OCH3-H2O]+. Combined with the calculation results, it is found that the S∴N hemibonded structure is competitive with the S⋯HN H-bonded structure, though only the latter structure is actually observed in [CH3SH-NH3]+. The spectral and theoretical results show that hemibonds can form between the second- (oxygen or nitrogen) and the third-period elements (sulfur) in the heterodimer clusters of [CH3SCH3-NH3]+ and [CH3SCH3-H2O]+. However, the S∴N and S∴O hemibonded structures are found competitive with the C⋯HN and CH⋯O H-bonded structures, respectively, and both the structures coexist. On the other hand, the O∴O hemibonded structure is much less stable than other hydrogen bonded (H-bonded) structures in [CH3OCH3-H2O]+, and it shows no clear contribution to the observed spectrum. This study provides direct spectroscopic evidence for the existence of S∴N and S∴O hemibonds in the gas phase and their competition with the H-bonds, which may be also fundamentally important in biological processes.

Hemoglobin/Red Blood Cell Distribution Width Ratio in Peripheral Blood Is Positively Associated with Prognosis of Patients with Primary Hepatocellular Carcinoma.

BACKGROUND The prognostic value of the hemoglobin/red blood cell distribution width ratio in primary hepatocellular carcinoma remains unknown. This study aimed to analyze the correlation between hemoglobin/red blood cell distribution width ratio and hepatocellular carcinoma prognosis. MATERIAL AND METHODS Medical records of hepatocellular carcinoma patients were analyzed retrospectively. The hemoglobin/red blood cell distribution width ratio cut-off value was determined as 0.987 by receiver operating characteristic curve analysis. Patients were divided into high- and low-level groups, and the clinical data were compared. The correlation among the ratio levels, progression-free survival, and overall survival was measured with univariate and multivariate Cox regression analyses. The prognostic utility of the ratio combined with alpha-fetoprotein was analyzed using Kaplan-Meier survival curves and log-rank detection, and the correlation between the ratio and tumor staging was studied using one-way analysis of variance. RESULTS This study included 252 patients. Sex, smoking and alcohol consumption history, body mass index, surgery, staging, platelet/lymphocyte ratio, and hemoglobin/red blood cell distribution width ratio were associated with progression-free and overall survival (P<0.05). The ratio, alpha-fetoprotein, hemoglobin, staging, and surgery were independent risk factors for progression-free survival (P<0.05), and the ratio, alpha-fetoprotein, hemoglobin, body mass index, HBsAg, staging, and surgery were independent risk factors for overall survival (P<0.05). Patients with low ratio levels and high alpha-fetoprotein levels had the worst prognosis. CONCLUSIONS Low hemoglobin/red blood cell distribution width ratio levels are associated with poor patient prognosis and are potential tumor prognosis markers.

Single-Molecule Junctions with Highly Improved Stability.

Single-molecule junctions (SMJs) have been fabricated using layers generated by diazonium electroreduction. This process creates a C-Au covalent bond between the molecule and the electrode. Rigid oligomers of variable length, based on porphyrin derivatives in their free base or cobalt complex forms, have been grafted on the surface. The conductance of the oligomers has been studied by a scanning tunneling microscopy break junction (STM-bj) technique and G(t) measurements, and the lifetime of the SMJs has been investigated. The conductance histograms indicate that charge transport in the porphyrins is relatively efficient and influenced by the presence of the cobalt center. With both systems, random telegraph G(t) signals are easily recorded, showing SMJ on/off states. The SMJs then stabilize and exhibit a surprisingly long lifetime around 10 s, and attenuation plots, obtained by both G(t) and STM-bj measurements, give identical values. This work shows that highly stable SMJs can be prepared using a diazonium grafting approach.

Unprecedented ON/OFF Ratios in Photoactive Diarylethene-Bisthienylbenzene Molecular Junctions.

Photoactive molecular junctions, based on 4 nm thick diarylethene (DAE) and 5 nm thick bisthienylbenzene (BTB) layers, were fabricated by electrochemical deposition. Total thickness was around 9 nm, that is, above the direct tunneling limit and in the hopping regime. The DAE units were switched between their open and closed forms. The DAE/BTB bilayer structure exhibits new electronic functions combining photoswitching and photorectification. The open form of DAE/BTB shows low conductance and asymmetric I-V curves while the closed form shows symmetric I-V curves and high conductance. More importantly, unprecedented ON/OFF current ratios of over 10 000 at 1 V were reproducibly measured.

Electrografting and Langmuir-Blodgett: Covalently Bound Nanometer-Thick Ordered Films on Graphite.

We present two different molecular organizations obtained from octadecylamine (ODA) molecules on a highly oriented pyrolytic graphite (HOPG) surface: (i) self-organized physisorbed ODA molecules lying flat on the surface and (ii) a strongly electrografted compact crystalline monolayer of ODA molecules standing up on the surface. This new structure is obtained by combining the Langmuir-Blodgett transfer of an ODA Langmuir film onto HOPG with oxidative electrografting. The presence of an organic film on HOPG is characterized by attenuated total reflectance-infrared spectroscopy and Raman spectroscopy, while atomic force microscopy and scanning tunneling microscopy allow the observation of the two molecular organizations with adsorbed molecules lying flat on HOPG or strongly grafted in an upright position on the HOPG surface. Interestingly, the second molecular organization preserves a hexagonal symmetry and its lattice parameters are intermediate between those of ODA Langmuir films and that of the HOPG underlying surface. The functionalization of surfaces with organic films is a major issue in the design of sensors with biomedical applications or organic electronics and energy storage devices and these structures may find applications in these fields.

Spectroscopic evidence of the C-N covalent bond formed between two interstellar molecules (ISM): acrylonitrile and ammonia.

Acrylonitrile (AN) and ammonia (NH3) are two important nitrogen-containing interstellar molecules in outer space, especially on Titan. Herein, we measured infrared (IR) spectra of neutral and cationic AN-NH3 complexes by VUV single-photon ionization combined with time-of-flight mass spectrometry. On combining IR spectra with the theoretical calculations, we found that the molecules prefer to form a single-ring cyclic H-bonded structure in the neutral AN-NH3 and (AN)2-NH3 clusters. However, after ionization of AN-NH3 and (AN)2-NH3 clusters, a new C-N-covalent bond is confirmed to form directly between AN and NH3, without any energy barrier in the cationic complexes. Moreover, in the ionized (AN)2-NH3 cluster, the covalent C-N bond prefers to form between AN and NH3 rather than the two AN groups. These results provide spectroscopic evidence of AN forming a new molecule with NH3, induced by VUV radiation. The formation of the new C-N bond broadens our knowledge on the evolution of the prebiotic nitrogen-containing molecules in space.