ROS induced the Rab26 promoter hypermethylation to promote cigarette smoking-induced airway epithelial inflammation of COPD through activation of MAPK signaling.

Cigarette smoking (CS) exposure-induced airway inflammatory responses drive the occurrence and development of emphysema and chronic obstructive pulmonary disease (COPD). However, its precise mechanisms have not been fully elucidated. In this study, we explore the role of Rab26 in CS exposure modulating the inflammatory response of airway epithelium and the novel mechanism of CS exposure regulation Rab26. These data showed that CS exposure and H2O2 (a type of ROS) suppressed the expression of Rab26 and increased the expression of DNMT3b in vivo and in vitro. GEO data analysis found the level of Rab26 was decreased in the lung tissue of COPD patients. CSE-induced ROS promoted DNA methylation of the Rab26 promoter and inhibited its promoter activity by elevating the DNMT3b level. Antioxidants N-Acetyl-l-cysteine (NAC), 5-Aza-2'-deoxycytidine (5-AZA) (DNA methylation inhibitor) and DNMT3B siRNA alleviated CSE's inhibitory effect on Rab26 expression in vitro. Importantly, NAC alleviated the improved expression of Rab26 and reduced DNMT3B expression, in the airway of smoking exposure as well as attenuated the inflammatory response in vivo. Overexpression of Rab26 attenuated CSE-induced production of inflammatory mediators through part inactivation of p38 and JNK MAPK. On the contrary, silencing Rab26 enhanced p38 and JNK activation and aggravated inflammatory response. These findings suggest that ROS-mediated Rab26 promoter hypermethylation is a critical step in cigarette smoking-induced airway epithelial inflammatory response. Restoring Rab26 in the airway epithelium might be a potential strategy for treating airway inflammation and COPD.

Protective effects of progesterone on pulmonary artery smooth muscle cells stimulated with Interleukin 6 via blocking the shuttling and transcriptional function of STAT3.

BACKGROUND: Sex hormone paradox is a crucial but unresolved issue in the field of pulmonary artery hypertension (PAH), and is thought to be related to different pathogenic factors. Inflammation is one of pathological mechanisms of PAH development. However, effects of sex hormones on the pulmonary vasculature under the condition of inflammation are still elusive. METHODS: Interleukin-6 (IL-6) was used as a representative inflammatory stimulator. Effects of 17ß-estradiol or progesterone on human pulmonary artery smooth muscle cells (PASMCs) were measured under the condition of IL-6. Cell functions of proliferation and migration were measured by Alarmar Blue, EdU assay, wound-healing assay and transwell chambers. We explored further mechanisms using western blot, immunofluorescence, co-immunoprecipitation, qPCR and chromatin immunoprecipitation. RESULTS: Our results revealed that IL-6 promoted the proliferation of PASMCs, but progesterone could reverse the adverse effect of IL-6. The protective effect was dependent on progesterone receptor (PGR). By interacting with signal transducer and activator of transcription 3 (STAT3), activated PGR could reduce the IL-6-induced nuclear translocation of STAT3 and prevent STAT3-chromatin binding in PASMCs, leading to the decreased transcription of downstream CCND1 and BCL2. Alternatively, progesterone slightly decreased the phosphorylation of pro-proliferative Erk1/2 and Akt kinases and upregulated the anti-proliferative pSmad1-Id1/2 axis in IL-6-incubated PASMCs. CONCLUSIONS: Progesterone played a protective role on PASMCs in the context of IL-6, by blocking the functions of STAT3. Our findings might assist in explaining the clinical phenomenon of better prognosis for women with PAH.

Comparative effectiveness and tolerability of targeted agents combined with chemotherapy in patients with HER2-positive gastroesophageal cancer: A network meta-analysis.

Background: Gastric cancer (GC) or gastroesophageal junction (GEJ) cancer with HER2 overexpression is highly invasive, with a poor prognosis. With the development of new targeted agents, which agents have ideal therapeutic effects must be determined. This network meta-analysis analyzed the effectiveness and tolerability of targeted agents combined with chemotherapy in HER2-positive GC/GEJ cancer. Methods: Public databases were searched from the date of inception to October 22, 2020. Randomized controlled trials (RCTs) on targeted agent-related regimens for HER2-positive advanced GC or GEJ cancer were included. Subgroup analyses based on publication language, first-line treatment, second/third-line treatment, and HER2 staining intensity were performed. Results: In total, 13 articles were included. The trastuzumabderuxtecan (TraD) and pertuzumab plus trastuzumab and chemotherapy (PerTraChemo) regimens were considered to have high effectiveness but low tolerability. In the subgroup analysis, PerTraChemo still had high effectiveness with low tolerability as the first-line therapy. As the second- or third-line therapy, TraD and lapatinib plus chemotherapy (LapChemo) had high effectiveness and moderate tolerability. In terms of overall survival (OS) time, PerTraChemo had a relative advantage in the immunohistochemistry (IHC) 2+/in situ hybridization (ISH)+ population, whereas TraD, PerTraChemo, and trastuzumab plus chemotherapy (TraChemo) had a relative advantage in the IHC3+ population. Conclusion: TraD had relative advantages as the second- or third-line therapy and in the IHC3 + population. PerTraChemo is a potential first-line therapy, but it requires further confirmation because the JACOB phase III clinical trial failed to confirm the superiority of PerTraChemo over TraChemo with regard to OS.

Noble Gas in a Ring.

We have designed a new type of molecule with a noble gas (Ng = Kr and Xe) atom in a six-membered ring. Their structures and stability have been studied by density functional theory and by correlated electronic structure calculations. The results showed that the six-membered ring is planar with very short Ng-O and Ng-N polar covalent bonds. The calculated energy barriers for all the unimolecular dissociation pathways are higher than 20 and 35 kcal/mol for Ng = Kr and Xe, respectively. The current study suggests that these molecules and their derivatives might be synthesized and observable at cryogenic conditions.

Theoretical Prediction on the New Types of Noble Gas Containing Anions OBONgO- and OCNNgO- (Ng = He, Ar, Kr and Xe).

The fluorine-less noble gas containing anions OBONgO- and OCNNgO- have been studied by correlated electronic structure calculation and density functional theory. The obtained energetics indicates that for Ng = Kr and Xe, these anions should be kinetically stable at low temperature. The molecular structures and electron density distribution suggests that these anions are stabilized by ion-induced dipole interactions with charges concentrated on the electronegative OBO and OCN groups. The current study shows that in addition to the fluoride ion, polyatomic groups with strong electronic affinities can also form stable noble gas containing anions of the type Y-…NgO.

Elevated serum procalcitonin level in patients with chronic kidney disease without infection: A case-control study.

BACKGROUND: Inflammation is a necessary component of chronic kidney disease (CKD) that can be attributed to an accumulation of toxins and a reduced clearance of proinflammatory cytokines. Procalcitonin (PCT) is a widely applied biomarker in the diagnosis of infection, and considering the presence of pre-existing inflammation in CKD patients, the PCT level could be high in such a population; however, no reference value for PCT in CKD patients has been available to date. METHODS: During the present study period, 361 CKD patients and 119 healthy controls were included. The PCT level and other biochemistry parameters were assayed by using a COBAS system. Statistical analysis was conducted to compare the differences in PCT levels and other biochemistry parameters between the two groups, and linear regression was used to assess the correlation between two variables. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the performance of PCT and the optimal cutoff value to differentiate between CKD patients and healthy controls. RESULTS: The PCT level in CKD patients was significantly higher than that in healthy controls, and among the CKD patients, the PCT level was increased with advanced clinical stage. Moreover, PCT was moderately correlated with CysC. The optimal off-value was 0.075 with a sensitivity of 94.7% and specificity of 90.8%. CONCLUSION: The PCT level was significantly higher in CKD patients than in healthy controls, and the reference value for CKD patients should be adjusted to avoid unnecessary antibiotic treatments which may pose a negative impact on residual renal function.

Treating Clinically Node-Negative Insular Thyroid Carcinoma without Prophylactic Central Compartment Neck Dissection Is Associated with Decreased Survival Regardless of T Staging and Administration of Radioactive Iodine Therapy: The First Evidence.

For the rare but aggressive insular thyroid carcinoma (ITC), there's no clear evidence to determine whether prophylactic central compartment neck dissection (CCND) is necessary for cN0 disease. This study provides the first evidence that treating cN0 ITC without prophylactic CCND is associated with decreased survival regardless of T staging and administration of RAI therapy. Background. Regarding the rare but aggressive insular thyroid carcinoma (ITC), the value of prophylactic central compartment neck dissection (CCND) for clinically node-negative (cN0) disease is unclear. We aimed to provide the first evidence. Methods. N0 and pN1a ITC patients were identified from the Surveillance, Epidemiology, and End Results database. These patients were divided into thyroid-surgery + CCND group (pN0/pN1a patients confirmed by CCND) and thyroid-surgery group (cN0 patients without CCND). Differences in overall survival (OS) and disease-specific survival (DSS) between the two groups were evaluated. Subgroup analyses were also conducted. Results. Of the overall 112 patients, 44 (39.3%) received CCND. On multivariate analyses, the lobectomy ± isthmusectomy/total-thyroidectomy (Lob/TT) group demonstrated poorer OS and DSS than the Lob/TT + CCND group (P < 0.05). When we separately analyzed patients treated by TT, multivariate analyses showed the TT group still revealed compromised OS and DSS than the TT + CCND group (P < 0.05). Furthermore, absence of CCND independently predicted decreased OS no matter whether radioactive iodine (RAI) was administered. Similar results were obtained for T3/T4 patients. Moreover, for T1/T2 patients receiving CCND, 0/12 died during the study period, while for T1/T2 patients without CCND, 8/23 (34.8%) died, 5/23 (21.7%) due to ITC. Conclusion. Regardless of T staging and RAI treatment, cN0-ITC patients without CCND had decreased survival compared with pN0/pN1a patients receiving CCND. Therefore, if a cN0 patient is diagnosed with ITC, prophylactic CCND may be considered as a secondary procedure (postoperatively diagnosed) or a primary procedure (preoperatively/intraoperatively diagnosed). Prospective studies are expected to validate the conclusion.

Anatomic extent of lymph node metastases as an independent prognosticator in node-positive major salivary gland carcinoma: A study of the US SEER database and a Chinese multicenter cohort.

BACKGROUND: We aimed to explore whether the anatomic extent of lymph node metastases (AE-LNM) could independently predict prognosis of node-positive major salivary gland carcinoma (MaSGC). METHODS: A total of 376 pathologically node-positive MaSGC patients were identified from the Surveillance, Epidemiology and End Results database and constituted the training cohort. Using the X-Tile program, these patients were divided into three groups based on AE-LNM degrees. Discrimination of overall survival (OS) and disease-specific survival (DSS) was evaluated and compared with the 8th American Joint Committee on Cancer (AJCC) pN classification. The results were externally validated by 220 patients in a Chinese multicenter cohort (Validation cohort). RESULTS: Using the training cohort, AE-LNM was divided into Extent 1 (spread to parotid LNs or level I), Extent 2 (spread to level II-IV) and Extent 3 (spread to level V or bilateral LNs or rare LNs). Regarding both OS and DSS, the AE-LNM model revealed clear separation of survival curves, while the pN classification failed to discriminate the prognosis of pN1 and pN2 patients. When we incorporated both the AE-LNM model and AJCC pN classification into the same multivariate Cox analyses, AE-LNM was still an independent prognostic factor, while the AJCC pN classification lost its significance. These results were externally validated by the validation cohort. CONCLUSION: AE-LNM is an independent nodal prognosticator for node-positive MaSGC and may have improved discriminative ability over the current AJCC pN classification. Integration of anatomic extent of LNM into the current AJCC N classification could be considered.

Altered serum levels of type I collagen turnover indicators accompanied by IL-6 and IL-8 release in stable COPD.

BACKGROUND: COPD, characterized by chronic inflammation and airway remodeling, has significant pathological alterations in composition and deposition of the extracellular matrix. The expression of procollagen 1 C-terminal peptide (PICP) and collagen type 1 C-terminal telopeptide (ICTP), two major by-products in the synthesis and degradation of collagen, was shown to be positively correlated with inflammatory mediator levels in previous studies. PURPOSE: In this study, we investigated whether the serum concentrations of PICP and ICTP were associated with the inflammation level for patients with stable COPD. PATIENTS AND METHODS: We collected serum samples from 25 control subjects and 20 patients with stable COPD from December 2011 to October 2012 in Shanghai Zhongshan Hospital and Shanghai Dahua Hospital. We determined concentrations of PICP, ICTP, C-reactive protein (CRP), IL-6, IL-8, and tumor necrosis factor (TNF)-α by using enzyme-linked immunosorbent assay methods. RESULTS: Demographic characteristics were comparable between the two groups. In patients with stable COPD, serum levels of CRP, IL-6, IL-8, and TNF-α were all elevated compared to control subjects, but only changes of IL-6 achieved statistical significance. Serum concentration of PICP was significantly elevated in patients with COPD, and level of ICTP was slightly decreased. Moreover, serum concentrations of PICP were positively correlated with the levels of both IL-6 and IL-8. CONCLUSION: The increased levels of serum PICP in COPD might indicate the condition of airway remodeling, and IL-6 and/or IL-8 might play an important role in stimulating collagen synthesis.

Identification of novel candidate genes involved in the progression of emphysema by bioinformatic methods.

PURPOSE: By reanalyzing the gene expression profile GSE76925 in the Gene Expression Omnibus database using bioinformatic methods, we attempted to identify novel candidate genes promoting the development of emphysema in patients with COPD. PATIENTS AND METHODS: According to the Quantitative CT data in GSE76925, patients were divided into mild emphysema group (%LAA-950<20%, n=12) and severe emphysema group (%LAA-950>50%, n=11). Differentially expressed genes (DEGs) were identified using Agilent GeneSpring GX v11.5 (corrected P-value <0.05 and |Fold Change|>1.3). Known driver genes of COPD were acquired by mining literatures and retrieving databases. Direct protein-protein interaction network (PPi) of DEGs and known driver genes was constructed by STRING.org to screen the DEGs directly interacting with driver genes. In addition, we used STRING.org to obtain the first-layer proteins interacting with DEGs' products and constructed the indirect PPi of these interaction proteins. By merging the indirect PPi with driver genes' PPi using Cytoscape v3.6.1, we attempted to discover potential pathways promoting emphysema's development. RESULTS: All the patients had COPD with severe airflow limitation (age=62±8, FEV1%=28±12). A total of 57 DEGs (including 12 pseudogenes) and 135 known driving genes were identified. Direct PPi suggested that GPR65, GNB4, P2RY13, NPSR1, BCR, BAG4, and IMPDH2 were potential pathogenic genes. GPR65 could regulate the response of immune cells to the acidic microenvironment, and NPSR1's expression on eosinophils was associated with asthma's severity and IgE level. Indirect merging PPi demonstrated that the interacting network of TP53, IL8, CCR2, HSPA1A, ELANE, PIK3CA was associated with the development of emphysema. IL8, ELANE, and PIK3CA were molecules involved in the pathological mechanisms of emphysema, which also in return proved the role of TP53 in emphysema. CONCLUSION: Candidate genes such as GPR65, NPSR1, and TP53 may be involved in the progression of emphysema.

Central Lymph Node Status has Significant Prognostic Value in the Clinically Node-Negative Tall-Cell Variant of Papillary Thyroid Cancer Regardless of T-Staging and Radioactive Iodine Administration: First Evidence From a Population-Based Study.

BACKGROUND: The prognostic value of central lymph node (CLN) status in papillary thyroid cancer (PTC) remains controversial. This study aimed to provide the first evidence on this issue for the aggressive tall-cell variant (TCV) subtype. METHODS: The study identified TCV patients from the Surveillance, Epidemiology, and End Results database. The Kaplan-Meier method, log-rank test, and multivariate Cox regression models were used for analysis. RESULTS: Of the 744 patients included, 404 were recorded as N0, which were pathologically or only clinically confirmed. Overall survival (OS) and cancer-specific survival (CSS) did not differ significantly between the N0 and pN1a patients (p > 0.05). To investigate the reason, the N0 patients were subdivided according to the number of examined lymph nodes (ELN). The patients with a N0 diagnosis confirmed by two or more ELNs (N0-e2+) showed significantly better outcomes than the pN1a patients and their N0 counterparts without ELN (N0-e0) (p < 0.05), whereas the N0-e0 and pN1a groups demonstrated comparable outcomes in both the log-rank and multivariate analyses (p > 0.05). Moreover, the subgroup analyses showed that even among the patients with early T-staging (T1-T2) or receipt of radioactive iodine (RAI) therapy, the N0-e0 patients still demonstrated compromised OS compared with the N0-e2+ group (p < 0.05). CONCLUSION: The cN0 patients without ELN (N0-e0) had outcomes similar to those of the pN1a patients, but showed a poorer OS than the N0-e2+ group regardless of T-staging and RAI administration, suggesting that occult CLN metastases might act as a negative prognosticator in cN0 TCV. Therefore, prophylactic central neck dissection might be considered for biopsy-proven cN0 TCV patients. Prospective studies are expected to further validate our conclusions.

Differentiation of human dental pulp stem cells into neuronal by resveratrol.

Dental pulp stem cells (DPSCs) have been proposed as a promising source of stem cells in nerve regeneration due to their close embryonic origin and ease of harvest. Resveratrol (RSV) is a natural polyphenolic and possesses many biological functions such as anti-inflammatory activity and protection against atherosclerosis and neuroprotective activities. There is increasing evidence showing that RSV plays a pivotal role in neuron protection and neuronal differentiation. In this study, we isolated DPSCs from impacted third molars and investigated whether RSV induces neuronal differentiation of DPSCs. To avoid loss of DPSCs multipotency, all the experiments were conducted on cells at early passages. RT-PCR results showed that RSV-treated DPSCs (RSV-DPSCs) significantly increased the expression of the neuroprogenitor marker Nestin. When RSV-DPSCs were differentiated with neuronal induction media (RSV-dDPSCs), they showed a cell morphology similar to neurons. The expression of neuronal-specific marker genes Nestin, Musashi, and NF-M in RSV-dDPSCs was significantly increased. Immunocytochemical staining and Western blot analysis showed that the expression of neuronal marker proteins, Nestin, and NF-M, was significantly increased in RSV-dDPSCs. Therefore, we have shown that RSV treatment, along with the use of neuronal induction media, effectively promotes neuronal cell differentiation of DPSCs.

Development of comprehensive nomograms for evaluating overall and cancer-specific survival of laryngeal squamous cell carcinoma patients treated with neck dissection.

BACKGROUND: Neck dissection for laryngeal squamous cell carcinoma (LSCC) patients could provide complementary prognostic information for AJCC N staging, like lymph node ratio (LNR). The aim of this study was to develop effective nomograms to better predict survival for LSCC patients treated with neck dissection. RESULTS: 2752 patients were identified and randomly divided into training (n = 2477) and validation (n = 275) cohorts. The 3- and 5-year probabilities of cancer-specific mortality (CSM) were 30.1% and 37.2% while 3- and 5-year death resulting from other causes (DROC) rate were 6.2% and 11.3%, respectively. 13 significant prognostic factors including LNR for overall (OS) and 12 (except race) for CSS were enrolled in the nomograms. Concordance index as a commonly used indicator of predictive performance, showed the nomograms had superiority over the no-LNR models and TNM classification (Training-cohort: OS: 0.713 vs 0.703 vs 0.667, CSS: 0.725 vs 0.713 vs 0.688; Validation-cohort: OS: 0.704 vs 0.690 vs 0.658, cancer-specific survival (CSS): 0.709 vs 0.693 vs 0.672). All calibration plots revealed good agreement between nomogram prediction and actual survival. MATERIALS AND METHODS: We identified LSCC patients undergoing neck dissection diagnosed between 1988 and 2008 from Surveillance, Epidemiology, and End Results (SEER) database. Optimal cutoff points were determined by X-tile program. Cumulative incidence function was used to analyze cancer-specific mortality (CSM) and death resulting from other causes (DROC). Significant predictive factors were used to establish nomograms estimating overall (OS) and cancer-specific survival (CSS). The nomograms were bootstrapped validated both internally and externally. CONCLUSIONS: Comprehensive nomograms were constructed to predict OS and CSS for LSCC patients treated with neck dissection more accurately.

Marital status and survival of patients with oral cavity squamous cell carcinoma: a population-based study.

BACKGROUND: The relationship between marital status and oral cavity squamous cell carcinoma (OCSCC) survival has not been explored. The objective of our study was to evaluate the impact of marital status on OCSCC survival and investigate the potential mechanisms. RESULTS: Married patients had better 5-year cancer-specific survival (CSS) (66.7% vs 54.9%) and 5-year overall survival (OS) (56.0% vs 41.1%). In multivariate Cox regression models, unmarried patients also showed higher mortality risk for both CSS (Hazard Ratio [HR]: 1.260, 95% confidence interval (CI): 1.187-1.339, P < 0.001) and OS (HR: 1.328, 95% CI: 1.266-1.392, P < 0.001). Multivariate logistic regression showed married patients were more likely to be diagnosed at earlier stage (P < 0.001) and receive surgery (P < 0.001). Married patients still demonstrated better prognosis in the 1:1 matched group analysis (CSS: 62.9% vs 60.8%, OS: 52.3% vs 46.5%). MATERIALS AND METHODS: 11022 eligible OCSCC patients were identified from Surveillance, Epidemiology, and End Results (SEER) database, including 5902 married and 5120 unmarried individuals. Kaplan-Meier analysis, Log-rank test and Cox proportional hazards regression model were used to analyze survival and mortality risk. Influence of marital status on stage, age at diagnosis and selection of treatment was determined by binomial and multinomial logistic regression. Propensity score matching method was adopted to perform a 1:1 matched cohort. CONCLUSIONS: Marriage has an independently protective effect on OCSCC survival. Earlier diagnosis and more sufficient treatment are possible explanations. Besides, even after 1:1 matching, survival advantage of married group still exists, indicating that spousal support from other aspects may also play an important role.

Theoretical Study on the Noble Gas Exchange Reactions of Ng + HNBNg'(+) → Ng' + HNBNg(+) (Ng, Ng' = He, Ne, Ar, Kr, and Xe).

High-level correlated electronic structure calculation and dual-level variational transition state theory with multidimensional tunneling calculation for rate constants have been performed on four noble gas exchange reactions [(1) He + HNBHe'(+) → He' + HNBHe(+), (2) He + HNBNe(+) → Ne + HNBHe(+), (3) Ne + HNBNe'(+) → Ne' + HNBNe(+), and (4) Ar + HNBAr'(+) → Ar' + HNBAr(+)] and on three (3)He isotopic analogues (He + HNB(3)He(+), (3)He + HNBHe(+), and (3)He + HNB(3)He(+)) of the first reaction. The classical barrier heights were predicted to be 8.9, 6.8, 5.7, and 5.5 kcal/mol for the four reactions, respectively. The tunneling effects were found to be important below 250 K for the He reactions and below 150 K for the Ne and Ar reactions. Kinetic helium isotope effects as large as 7.8 at 100 K were predicted for the (3)He + HNB(3)He(+) reaction. Additionally, the structures and energies of the Kr + HNBKr'(+) and Xe + HNBXe'(+) systems have also been studied.

Kinetics and Mechanism of the Oxidation of Cyclic Methylsiloxanes by Hydroxyl Radical in the Gas Phase: An Experimental and Theoretical Study.

The ubiquitous presence of cyclic volatile methylsiloxanes (cVMS) in the global atmosphere has recently raised environmental concern. In order to assess the persistence and long-range transport potential of cVMS, their second-order rate constants (k) for reactions with hydroxyl radical ((•)OH) in the gas phase are needed. We experimentally and theoretically investigated the kinetics and mechanism of (•)OH oxidation of a series of cVMS, hexamethylcyclotrisiloxane (D3), octamethycyclotetrasiloxane (D4), and decamethycyclopentasiloxane (D5). Experimentally, we measured k values for D3, D4, and D5 with (•)OH in a gas-phase reaction chamber. The Arrhenius activation energies for these reactions in the temperature range from 313 to 353 K were small (-2.92 to 0.79 kcal·mol(-1)), indicating a weak temperature dependence. We also calculated the thermodynamic and kinetic behaviors for reactions at the M06-2X/6-311++G**//M06-2X/6-31+G** level of theory over a wider temperature range of 238-358 K that encompasses temperatures in the troposphere. The calculated Arrhenius activation energies range from -2.71 to -1.64 kcal·mol(-1), also exhibiting weak temperature dependence. The measured k values were approximately an order of magnitude higher than the theoretical values but have the same trend with increasing size of the siloxane ring. The calculated energy barriers for H-atom abstraction at different positions were similar, which provides theoretical support for extrapolating k for other cyclic siloxanes from the number of abstractable hydrogens.

Highly Selective Dissociation of a Peptide Bond Following Excitation of Core Electrons.

The controlled breaking of a specific chemical bond with photons in complex molecules remains a major challenge in chemistry. In principle, using the K-edge absorption of a particular atomic element, one might excite selectively a specific atomic entity in a molecule. We report here highly selective dissociation of the peptide bonds in N-methylformamide and N-methylacetamide on tuning the X-ray wavelength to the K-edge absorption of the atoms connected to (or near) the peptide bond. The high selectivity (56-71%) of this cleavage arises from the large energy shift of X-ray absorption, a large overlap of the 1s orbital and the valence π* orbital that is highly localized on a peptide bond with antibonding character, and the relatively low bond energy of the peptide bonds. These characteristics indicate that the high selectivity on bond dissociation following core excitation could be a general feature for molecules containing peptide bonds.

Continuous renal replacement therapy in children with multiple organ dysfunction syndrome: A case series

There is a lack of definitive information regarding the precise indications, implementation, and outcomes of continuous renal replacement therapy (CRRT) for the treatment of critically ill children. Six children (three boys, three girls) aged from 3 days to 8 years, all of whom had multiple organ failure, were submitted to bedside CRRT using M60 filter membranes. Modified Port carbonate formula was used and clotting time was maintained between 20 and 30 minutes. Activated partial thromboplastin time was 1.5- to 2-fold normal. One patient discontinued treatment due to family decision. Marked improvements were seen in the remaining five patients, including normalization of blood urea nitrogen and creatinine levels, stabilization of electrolytes, and improvements in markers of organ function. Of note, one patient (a six-year-old male) underwent the treatment for 241 hours. All five patients were subsequently discharged and recovered uneventfully. CRRT is effective for the management of children who are critically ill due to multiple organ failure.

Core excitation, specific dissociation, and the effect of the size of aromatic molecules connected to oxygen: phenyl ether and 1,3-diphenoxybenzene.

Near-edge X-ray absorption fine structure (NEXAFS) spectra of phenyl ether at the carbon K-edge and 1,3-diphenoxybenzene at both the carbon and oxygen K-edges were measured in the total ion yield mode using X-rays from a synchrotron and a reflectron time-of-flight mass spectrometer. Time-dependent density functional theory was adopted to calculate the carbon and oxygen K-edge NEXAFS spectra of phenol, phenyl ether, and 1,3-diphenoxybenzene. The assignments and a comparison of the experimental and calculated spectra are presented. The mass spectra of ionic products formed after X-ray absorption at various excitation energies are also reported. Specific dissociations were observed for the 1s → π* transition of phenyl ether. In comparison with phenol and phenyl ether, the dependence of the fragmentation on the excitation site and destination state was weak in 1,3-diphenoxybenzene, likely as a result of delocalization of the valence electrons and rapid randomization of energy.

Theoretical prediction of new noble-gas molecules FNgBNR (Ng = Ar, Kr, and Xe; R = H, CH3, CCH, CHCH2, F, and OH).

We have computationally predicted a new class of stable noble-gas molecules FNgBNR (Ng = Ar, Kr, Xe; R = H, CH3, CCH, CHCH2, F, and OH). The FNgBNR were found to have compact structures with F-Ng bond lengths of 1.9-2.2 Å and Ng-B bond lengths of ~1.8 Å. The endoergic three-body dissociation energies of FNgBNH to F + Ng + BNH were calculated to be 12.8, 31.7, and 63.9 kcal mol(-1), for Ng = Ar, Kr, and Xe, respectively at the CCSD(T)/CBS level. The energy barriers of the exoergic two-body dissociation to Ng + FBNH were calculated to be 16.1, 24.0, and 33.2 kcal mol(-1) for Ng = Ar, Kr, and Xe, respectively. Our results showed that the dissociation energetics is relatively insensitive to the identities of the terminal R groups. The current study suggested that a wide variety of noble-gas containing molecules with different types of R groups can be thermally stable at low temperature, and the number of potentially stable noble-gas containing molecules would thus increase very significantly. It is expected some of the FNgBNR molecules could be identified in future experiments under cryogenic conditions in noble-gas matrices or in the gas phase.