Diazene Chemistry: Metal-Free Models of N2 Reduction Intermediates.

Interest in main group chemistry related to the Haber-Bosch process has drawn less attention than that of transition metal species. Herein, we show that the steric demands in (tBuO2CN)2 block initial interaction of B(C6F5)3 with nitrogen and prompt loss of methylpropene and CO2 to diazene (N2H2) borane adduct 1 and the analogous hydrazine (N2H4) adduct 2. These species react with basic phosphines to give anions of 3 and 5 containing N2H and N2H3 fragments, respectively. While these species are not derived directly from N2, they represent metal-free species containing N2Hn (n = 1-4) fragments, which model plausible intermediates in the reduction of N2.

Alkoxyphosphorane/Borane Cooperative Alkylations: A Frustrated Lewis Pair Version of the Mitsunobu Reaction.

The combination of the alkoxyphosphoranes, Ph2 P(OR)(O2 C6 Cl4 ) and the borane B(C6 F5 )3 generates the zwitterions 3 which act as FLP to effect the alkylation of several nucleophiles affording C-C, C-N, C-H and C-Cl coupling products. A DFT study shows the reaction proceeds via an FLP activation pathway generating an alkoxyphosphonium intermediate which effects the alkylation of the nucleophiles, akin to the Mitsunobu reaction.

Development of psychological resilience and associations with emotional and behavioral health among preschool left-behind children.

PURPOSE: This study aimed to explore the development of psychological resilience and its associations with emotional and behavioral health among preschool left-behind children (LBC). METHODS: LBC in 26 preschools of Fuyang City, Hefei City, and Maanshan City of Anhui Province were included at baseline survey; and baseline children in the junior and middle classes of preschools as targeted samples were recruited for the 1-year follow-up. Multivariable linear regression models were performed to examine associations of psychological resilience with emotional and behavioral health. RESULTS: In total, 1463 LBC were included at baseline and 568 of the 905 targeted LBC completed the 1-year follow-up. Change patterns of psychological resilience were identified as the stable-high pattern (19.0%), increasing pattern (18.3%), declining pattern (15.9%), and stable-low pattern (46.8%). The results showed that psychological resilience at baseline was positively associated with later dietary behavior habits and prosocial behaviors, and negatively associated with later problematic behaviors and sleep problems. In addition, children with the declining pattern had more problematic behaviors and sleep problems, and fewer prosocial behaviors at follow-up. Children with the increasing pattern and stable-high pattern had more prosocial behaviors, better dietary behavior habits, and fewer problematic behaviors and sleep problems at follow-up. CONCLUSIONS: The majority of preschool LBC had lower psychological resilience and its level among some LBC changed during the follow-up. Higher psychological resilience was a protective factor for emotional and behavioral health. Timely assessing psychological resilience and then strengthening it are needed to promote the emotional and behavioral health of preschool LBC.

The association between family function and sleep disturbances of preschool children in rural areas of China: a cross-sectional study.

This study aimed to explore the association between family function and sleep disturbances in preschool children in rural areas of China. Caregivers of preschool children completed sociodemographic questionnaires, the Children's Sleep Habits Questionnaire (CSHQ), the Self-rating Anxiety Scale (SAS) and the Family APGAR scale. Using sleep disturbances in children as the dependent variable, family function and other related factors as independent variables, binary logistic regression analyses were performed to examine associations between family function and sleep disturbances in children. A total of 3,636 caregivers of preschool children were enrolled in our study, and the prevalence of sleep disturbances among their preschool children was 89.4%. In our study, lower family function was associated with higher risk of sleep disturbances among preschool children. After adjusting for age (years), education level of mother, discipline attitudes of father and mother, only child status and caregivers' anxiety, the associations were statistically significant both in families of which caregivers of children are their parents or other relatives. (AOR for parents = 1.487, 95% CI:1.152-1.919, P = 0.002; AOR for other relatives = 1.963, 95% CI:1.302-2.958, P = 0.001). Our study results indicated that family function was associated with sleep disturbances in preschool children, and future high-quality cohort studies are needed to explore this topic in more detail.

A distributed lag non-linear time-series study of ambient temperature and healthcare-associated infections in Hefei, China.

Little is known about the effects of temperature on healthcare-associated infections (HAIs). A distributed lag non-linear model was used to estimate the association between ambient temperature and HAIs in Hefei, China. In total, 9,592 HAIs were included. The effect of low temperature (-0.1°C, 2.5th percentile) was significant on the current day (RR = 1.108, 95%CI:1.003-1.222), and then appeared on the 4th day (RR = 1.045, 95%CI:1.007-1.084) and the 5th day (RR = 1.033, 95%CI:1.006-1.061). The cumulative lag effects of low temperature lasted from the 5th to 10th days (RR = 1.123-1.143), and a long-term cumulative lag effect was observed on the 14th day (RR = 1.157, 95%CI:1.001-1.338). The lag effect of high temperature (31.0°C, 97.5th percentile) was not statistically significant. However, the effects of temperatures on HAIs were not significant among gender or age subgroups. This study suggests that the low temperatures have acute and lag effects on HAIs in Hefei, China.

Isobaric Stable Isotope N-Phosphorylation Labeling (iSIPL) for Ultrasensitive Proteome Quantification.

Stable isotope chemical labeling methods have been widely used for high-throughput mass spectrometry (MS)-based quantitative proteomics in biological and clinical applications. However, the existing methods are far from meeting the requirements for high sensitivity detection. In the present study, a novel isobaric stable isotope N-phosphorylation labeling (iSIPL) strategy was developed for quantitative proteome analysis. The tryptic peptides were selectively labeled with iSIPL tag to generate the novel reporter ions containing phosphoramidate P-N bond with high intensities under lower collision energies. iSIPL strategy are suitable for peptide sequencing and quantitative analysis with high sensitivity and accuracy even for samples of limited quantity. Furthermore, iSIPL coupled with affinity purification and mass spectrometry was applied to measure the dynamics of cyclin dependent kinase 9 (CDK9) interactomes during transactivation of the HIV-1 provirus. The interaction of CDK9 with PARP13 was found to significantly decrease during Tat-induced activation of HIV-1 gene transcription, suggesting the effectiveness of iSIPL strategy in dynamic analysis of protein-protein interaction in vivo. More than that, the proposed iSIPL strategy would facilitate large-scale accurate quantitative proteomics by increasing multiplexing capability.

The Varied Frustrated Lewis Pair Reactivity of the Germylene Phosphaketene (CH{(CMe)(2,6-i Pr2 C6 H3 N)}2 )GePCO.

The germylene species (CH{(CMe)(2,6-iPr2 C6 H3 N)}2 )GePCO 1 is shown to react with the Lewis acids (E(C6 F5 )3 E=B, Al). Nonetheless, 1 participates in FLP chemistry with electron deficient alkynes or olefins, acting as an intramolecular FLP. In contrast, in the presence of B(C6 F5 )3 and an electron rich alkyne, 1 behaves as Ge-based nucleophile to effect intermolecular FLP addition to the alkyne. This reactivity demonstrates that the reaction pathway is controlled by the nature of the electrophile and nucleophile generated in solution, as revealed by extensive DFT calculations.

Ambiphilic Behavior of Ge(II)-Pseudohalides in Inter- and Intramolecular Frustrated Lewis Pair Alkyne Addition Reactions.

The reaction of the germylene chloride (NacNac)GeCl (1, NacNac = CH{(CMe)(2,6-iPr2C6H3N)}2), phenylacetylene, and B(C6F5)3 gives the intermolecular frustrated Lewis pair (FLP) addition product 2. In this case, the Ge(II) center acts as a base. In contrast, the analogous reaction of germylene thiocyanate 3 reacts independently with B(C6F5)3 to give the germylene cation salt [(NacNac)Ge][SCNB(C6F5)3] 4. Subsequent in the presence of alkynes, the Ge(II) cation and γ-C of 4 act as a Lewis acidic and basic center, respectively, to affect the addition of alkynes, affording products [(NacNac)Ge(RCCR')][SCNB(C6F5)3] 5 and 6. Compound 4 also reacts with Me3SiCN to give the cyanide-bridged Ge/B species 7, which also reacts with phenylacetylene to give CN abstraction and intramolecular addition yielding the salt [(NacNac)Ge(PhCCH)][NCB(C6F5)3] 8. Despite the similarity of 1 and 3, DFT calculations show that the highest occupied molecular orbital (HOMO) of 1 is mainly located at the more sterically hindered germylene center, while the HOMO of 3 is located on the less sterically hindered NCS group, prompting markedly different FLP addition products.

Is metformin use associated with a reduced risk of oesophageal cancer? A systematic review and meta-analysis.

OBJECTIVES: Studies on the association between metformin use and the risk of oesophageal cancer (OC) have generated controversial findings. This updated meta-analysis was conducted to reassess the effects of metformin on OC. METHODS: A comprehensive search strategy was conducted to select relevant studies from origination to February 2021. Heterogeneity was evaluated through the Q test and I2 statistics. HRs and 95% CIs were pooled through either random-effect or fixed-effect models. Meta-regression, subgroup analyses, sensitivity analysis and publication bias diagnosis were also performed. RESULTS: Seven studies with 5 426 343 subjects were included. Metformin use was associated with reduced risk of OC (HR=0.69, 95% CI 0.54 to 0.87, p<0.001). Sensitivity analysis suggested that the results were relatively stable. CONCLUSION: Metformin is associated with a reduced risk of OC. More well-designed studies are still needed to further elaborate on these associations. PROSPERO REGISTRATION NUMBER: CRD42021237127.

Does Famotidine Reduce the Risk of Progression to Severe Disease, Death, and Intubation for COVID-19 Patients? A Systemic Review and Meta-Analysis.

BACKGROUND: Famotidine was reported to potentially provide benefits to Coronavirus Disease 2019 (COVID-19) patients. However, it remains controversial whether it is effective in treating COVID-19. AIMS: This study aimed to explore whether famotidine use is associated with reduced risk of the severity, death, and intubation for COVID-19 patients. METHODS: This study was registered on International Prospective Register of Systematic Reviews (PROSPERO) (ID: CRD42020213536). A comprehensive search was performed to identify relevant studies up to October 2020. I-squared statistic and Q-test were utilized to assess the heterogeneity. Pooled risk ratios (RR) and 95% confidence intervals (CI) were calculated through the random effects or fixed effects model according to the heterogeneity. Subgroup analyses, sensitivity analysis, and publication bias assessment were also conducted. RESULTS: Five studies including 36,635 subjects were included. We found that famotidine use was associated with a statistically non-significant reduced risk of progression to severe disease, death, and intubation for Coronavirus Disease 2019 (COVID-19) patients (pooled RR was 0.82, 95% CI = 0.52-1.30, P = 0.40). CONCLUSION: Famotidine has no significant protective effect in reducing the risk of developing serious illness, death, and intubation for COVID-19 patients. More original studies are needed to further clarify whether it is associated with reduced risk of the severity, death, and intubation for COVID-19 patients.

The relationship between psychological resilience and emotion regulation among preschool left-behind children in rural China.

To evaluate the relationship between resilience and emotion regulation among preschool left-behind children (LBC) in rural China. A total of 620 preschool LBC were enrolled from rural areas in Anhui province, China. Multivariate logistic regression was used to evaluate the associations between resilience and variables. The results showed that 20.2% of LBC had higher resilience. Emotion regulation was correlated with resilience among preschool LBC. Children with higher cognitive reconstruction (adjusted OR (AOR) = 0.349,95%CI:0.249-0.489), passive dealing (AOR = 0.577, 95%CI:0.411-0.810), alternative action (AOR = 0.369, 95%CI:0.267-0.510) and self-comforting (AOR = 0.441, 95%CI:0.315-0.619) would have lower risk of low resilience. Our findings suggest that strengthening emotion regulation could promote psychological resilience and prevent adverse developments in LBC.

Performance of commercially available anti-HDV enzyme-linked immunosorbent assays in Taiwan.

BACKGROUND: Hepatitis D virus (HDV) infection is a major global health issue around the world. There are approximately 15-20 million individuals infected with HDV worldwide. HDV infection usually causes increased mortality compared with infection with hepatitis B virus (HBV) alone. However, testing for the detection of HDV is not widely available in Taiwan. Therefore, the General Biologicals Corporation (GB) HDV Ab kit was developed for detecting anti-HDV antibodies. METHODS: A total of 913 serum and 462 EDTA-treated plasma samples were obtained from HBsAg-positive individuals in three hospitals in Taiwan from June 2014 to November 2017. We used three commercially available ELISA kits, DiaPro HDV Ab, DiaSorin ETI-AB-DELTAK-2 and GB HDV Ab, which were utilized strictly according to the instructions of the manufacturers. RESULTS: A comparative study of the results from the GB HDV Ab kit and the other commercial ELISA kits (DiaPro and DiaSorin) was performed to determine their efficacy for anti-HDV detection. The results indicated that the sensitivity of the GB HDV Ab kit for serum and EDTA samples was 100% compared to that of the DiaPro and DiaSorin kits, whereas the specificity for serum and EDTA samples was 99.3 and 98.1%, respectively. In addition, the overall agreement of the results of the GB HDV Ab kit for the serum and EDTA samples was 99.3 and 98.3%, respectively. It is worth noting that the performance of the GB HDV Ab kit was not affected by interference from triglyceride, bilirubin, hemoglobin, or human anti-mouse antibody. The limit of detection of the GB HDV Ab kit is approximately 100-fold lower than that of the other two commercial kits. CONCLUSIONS: The GB HDV Ab kit, which presented equivalent sensitivity and specificity compared to both certified anti-HDV kits, would be a suitable kit for HDV diagnosis in Taiwan.

Prevalence of infections and antimicrobial use among hemodialysis outpatients: A prospective multicenter study.

Hemodialysis patients are vulnerable to infectious diseases and frequent receipt of antimicrobial agents. The aim of this study was to describe the prevalence and characteristics of infections and antimicrobials use among hemodialysis outpatients. We utilized the dialysis event surveillance protocol developed by the National Healthcare Safety Network to conduct a prospective multicenter study in Anhui, China. A total of 41 dialysis centers involving 7393 outpatients were included. Fistula was the most common type of vascular access (85.3%), followed by tunneled central line (12.7%), and non-tunneled central line (1.2%). There were 118 dialysis events with an overall pooled events rate of 1.60 per 100 patient-months. Intravenous antimicrobial start, positive blood culture, and pus, redness, or increased swelling at the vascular access site were detected at rates of 0.91, 0.23, and 0.46 per 100 patient-months, respectively. The prevalence of dialysis events was commonly higher in patients with a central line, and lower in patients with a fistula. Hemodialysis outpatients also had the noteworthy risks of nonaccess infections. Older age, female gender, and having a central line were associated with the increased risk of dialysis events. Findings recommend that regular monitoring and improvement strategies are warranted in management of infections among hemodialysis outpatients.

Dynamics and predictors of resilience in Chinese rural children: a follow-up study.

The present study attempted to investigate dynamics and predictors of resilience amongst Chinese children using prospective data. Totally 816 children completed the resilience measurement at baseline and one-year follow-up. Multivariate logistic regression was used to examine associations between high resilience and predictor variables. Mean resilience scores increased during the one-year follow-up (t = -2.35, P = 0.019). Although the proportions of high and low resilience were relatively stable, whereas 28% of children had inconsistent resilience level during the follow-up. Multivariable logistic regression analysis showed that participants' parents having secondary school (adjusted OR (aOR) = 1.67, 95%CI = 1.14-2.44) or higher (aOR = 2.53, 95%CI = 1.51-4.24) education level, and high quality of life (aOR = 1.81, 95%CI = 1.20-2.73) were positively associated with high resilience, whereas moderate family function obstacles (aOR = 0.47, 95%CI = 0.34-0.67), abuse experience (aOR = 0.68, 95%CI = 0.50-0.92), and significant depression symptoms (aOR = 0.47, 95%CI = 0.28-0.77) were negatively associated with high resilience. Results highlight that resilience levels were not merely static trait and improved over one year among Chinese children. Findings would deepen understanding of resilience change and provide potential targets of resilience-focused intervention in children.

An 8-year point-prevalence surveillance of healthcare-associated infections and antimicrobial use in a tertiary care teaching hospital in China.

Healthcare-associated infections (HAIs) are a major worldwide public-health problem, but less data are available on the long-term trends of HAIs and antimicrobial use in Eastern China. This study describes the prevalence and long-term trends of HAIs and antimicrobial use in a tertiary care teaching hospital in Hefei, Anhui, China from 2010 to 2017 based on annual point-prevalence surveys. A total of 12 505 inpatients were included; 600 HAIs were recorded in 533 patients, with an overall prevalence of 4.26% and a frequency of 4.80%. No evidence was found for an increasing or decreasing trend in prevalence of HAI over 8 years (trend χ2 = 2.15, P = 0.143). However, significant differences in prevalence of HAI were evident between the surveys (χ2 = 21.14, P < 0.001). The intensive care unit had the highest frequency of HAIs (24.36%) and respiratory tract infections accounted for 62.50% of all cases; Escherichia coli was the most common pathogen (16.67%). A 44.13% prevalence of antimicrobial use with a gradually decreasing trend over time was recorded. More attention should be paid to potential high-risk clinical departments and HAI types with further enhancement of rational antimicrobial use.

The association between orthostatic hypotension and dementia: A meta-analysis of prospective cohort studies.

OBJECTIVES: As for the association between orthostatic hypotension (OH) and dementia, results of published studies are inconsistent; therefore, current substantive conclusions have yet been obtained. This meta-analysis was conducted in hopes of producing progress in this topic. METHODS: A systematic database search was performed towards electronic databases including Chinese Biomedical Database, PubMed, Web of Science, Wiley Online Library, ScienceDirect, and the Cochrane Library. Five prospective cohort studies were included. Summary hazard ratio (HR) estimates with 95% confidence intervals (CIs) were calculated by random-effects model. Statistical heterogeneity was assessed with the Cochran Q test and I2 statistic. A sensitivity analysis was also conducted in this meta-analysis. RESULTS: A 22.4% higher prevalence of dementia in subjects with OH was obtained (adjusted pooled HR was 1.224; 95% CI: 1.106-1.354; P < .001). This meta-analysis also showed significant associations between OH and 2 dementia subtypes: Alzheimer disease (adjusted pooled HR was 1.175; 95% CI: 1.022-1.351; P = .023) and Vascular dementia (adjusted pooled HR was 1.403; 95% CI: 1.042-1.889; P = .026), respectively. CONCLUSIONS: Orthostatic hypotension is positively associated with the overall prevalence of dementia, and it may contribute to the prevalence of Alzheimer disease and Vascular dementia as well.

Mechanism of Nickel-Catalyzed Selective C-N Bond Activation in Suzuki-Miyaura Cross-Coupling of Amides: A Theoretical Investigation.

In textbooks, the low reactivity of amides is attributed to the strong resonance stability. However, Garg and co-workers recently reported the Ni-catalyzed activation of robust amide C-N bonds, leading to conversions of amides into esters, ketones, and other amides with high selectivity. Among them, the Ni-catalyzed Suzuki-Miyaura coupling (SMC) of N-benzyl-N-tert-butoxycarbonyl (N-Bn-N-Boc) amides with pinacolatoboronate (PhBpin) was performed in the presence of K3PO4 and water. Water significantly enhanced the reaction. With the aid of density functional theory (DFT) calculations, the present study explored the mechanism of the aforementioned SMC reaction as well as analyzed the weakening of amide C-N bond by N-functionalization. The most favorable pathway includes four basic steps: oxidative addition, protonation, transmetalation, and reductive elimination. Comparing the base- and water-free process, the transmetalation step with the help of K3PO4 and water is significantly more facile. Water efficiently protonates the basic N(Boc) (Bn) group to form a neutral HN(Boc) (Bn), which is easily removed. The transmetalation step is the rate-determining step with an energy barrier of 25.6 kcal/mol. Further, a DFT prediction was carried out to investigate the full catalytic cycle of a cyclic (amino) (aryl)carbene in the Ni-catalyzed SMC of amides, which provided clues for further design of catalysts.

Association of methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism with preterm delivery and placental abruption: a systematic review and meta-analysis.

INTRODUCTION: The aim of this study was to summarize evidence on the association between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and odds of preterm delivery and placental abruption. MATERIAL AND METHODS: PubMed, EMBASE, CBM (Chinese Biomedical Database) and CNKI (Chinese National Knowledge Infrastructure) were searched to identify eligible studies published in English or Chinese before 12 August 2014. The pooled odds ratios (ORs) with 95% confidence intervals were estimated for the association of MTHFR C677T polymorphism with preterm delivery and placental abruption using random effects models. RESULTS: A total of 22 studies that met inclusion and exclusion criteria were included in this meta-analysis. Regardless of the genetic model tested we found no statistically significant association of MTHFR C677T polymorphism with preterm delivery or placental abruption. Funnel plots inspections, Begg's test and Egger's test did not show evidence of publication bias. CONCLUSIONS: This meta-analysis demonstrated that overall there was no association of MTHFR C677T polymorphism with preterm delivery or placental abruption.

Methylenetetrahydrofolate reductase (MTHFR) polymorphism susceptibility to schizophrenia and bipolar disorder: an updated meta-analysis.

Previous studies examining the possible role of the methylenetetrahydrofolate reductase (MTHFR) polymorphisms in the development of schizophrenia (SZ) and bipolar disorder (BPD) have provided inconclusive findings, this meta-analysis was therefore designed to get a more reliable assessment. A total of 38 articles were identified through a search of electronic databases, up to 27 February 2014. Odds ratios (ORs) with 95% confidence interval (CIs) were calculated using random effects models. Meta-analysis showed that MTHFR C677T was significantly associated with SZ, the highest OR was found for the recessive model (for TT vs. CT + CC: OR = 1.34, 95% CI: 1.18-1.53); a marginal association of MTHFR C677T with increased risk of BPD has also been found for the recessive model (OR = 1.26, 95% CI: 1.00-1.59). Subgroup analysis by ethnicity indicated that the significant association with SZ and BPD existed among Asian and African populations, but not for the white. MTHFR A1298C was significant associated with SZ, the highest OR for the dominant model (OR = 1.13, 95% CI: 1.03-1.24). Subgroup analysis indicated a significant association with SZ existed in Asian populations, not among the white populations and no significant association was detected between the MTHFR A1298C and BPD in all groups. We conclude that MTHFR polymorphism is associated with SZ and BPD among Asian, African populations, but not the white.

Nickel-catalyzed one-pot tandem 1,4-1,2-addition of P(O)H compounds to 1,10-phenanthrolines.

A novel and efficient nickel-catalyzed tandem 1,4-1,2-addition of P(O)H compounds to 1,10-phenanthrolines forming various 2,4-diphosphono-1,2,3,4-tetrahydro-1,10-phenanthrolines has been developed. This reaction breaks up the aromatic stabilization and directly introduces two phosphorus moieties in one single step. This finding is the first example of transition-metal-catalyzed double hydrophosphonylation of 1,10-phenanthrolines.