The impact of Lewis acid variation on reactions with di-tert-butyl diazo diesters.

Reactions of (tBuO2CN)2 with Lewis acids and FLPs have previously been shown to prompt the formation of diazene compounds. In this work, we show that the reaction of (tBuO2CN)2 with 9-BBN leads to a bicyclic heterocyclic product (tBuOCO(BBN)CN)21. In contrast, the reactions of (tBuO2CN)2 with BF3 or [Et3Si][B(C6F5)4] lead to the isolation of [tBuNHNH2tBu][BF4] 2 and [tBuN(H)NtBu][B(C6F5)4] 3, respectively. The mechanism for the formation of 2 is probed computationally, demonstrating that steric and electronic considerations of the Lewis acid impact the reaction pathway.

The Lewis superacidic aluminium cation: [(NHC)Al(C6F5)2].

The aluminium salt [(NHC)Al(tol)(C6F5)2][B(C6F5)4], (NHC = C3H2(N(iPr2C6H3))2) is shown to behave as a Lewis superacid as it abstracts fluoride from [SbF6]-. It also acts as a Lewis acid catalyst for hydrosilyation, hydrodefluorination and Friedel-Crafts reactions.

Correction: Stannyl phosphaketene as a synthon for phosphorus analogues of ß-lactams.

Correction for 'Stannyl phosphaketene as a synthon for phosphorus analogues of ß-lactams' by Yong-an Luo et al., Chem. Commun., 2023, https://doi.org/10.1039/d3cc03117a.

A prospective surveillance study of healthcare-associated infections in an intensive care unit from a tertiary care teaching hospital from 2012-2019.

Healthcare-associated infections (HAIs) continue to be the most common adverse event affecting critically ill inpatients in intensive care units (ICUs). Limited data exist in the English literature on the epidemiology of HAIs in ICUs from China. The purpose of this prospective study was to understand the prevalence and trends of HAIs in the ICU to guide clinicians to take effective prevention and control measures. In total, 20 ICU beds in the hospital from January 2012 to December 2019 were selected for surveillance. HAI diagnosis and device-associated infection surveillance were based on the criteria set forth by the original Ministry of Health of the People's Republic of China. The full-time staff for HAI management monitored all patients who stayed in the ICU > 48 hours during the study period and calculated the device utilization ratio and device-associated infection rate. The rate of HAIs and the adjusted rate were 18.78 per 1000 patient-days and 5.17 per 1000 patient-days, respectively. The rates of ventilator-associated pneumonias, catheter-associated urinary tract infections, and central line-associated bloodstream infections were 22.68 per 1000 device-days, 2.40 per 1000 device-days, and 2.27 per 1000 device-days, respectively. A total of 731 pathogenic bacteria were detected in the patients with HAIs. Gram-negative and gram-positive bacteria accounted for 67.44% and 16.83%, respectively. Continuous target monitoring, regular analysis of high-risk factors, and timely intervention measures could effectively reduce HAIs in the ICU. Additionally, these findings could be used for developing new strategies to prevent and control HAIs in ICUs.

Stannyl phosphaketene as a synthon for phosphorus analogues of ß-lactams.

The reaction of the stannyl phosphaketene (Nacnac)SnPCO 1 (Nacnac = CH{(CMe)(2,6-iPr2C6H3N)}2) with B(C6F5)3 produced the 1,4-addition product of (Nacnac)SnPCO(B(C6F5)3). However, the corresponding reactions in the presence of dimethyl maleate, diisopropyl fumarate or diethyl-but-2-ynedioate gave [2+2] addition yielding four-membered phosphacycles, ((Nacnac)Sn(MeO2C))CHPC(OB(C6F5)3)CH(CO2Me), [(C6F5)3B)PC(OSn)C(CO2Me)CH(CO2Me)]2, (Nacnac)Sn(iPrO2C)CC(OAl(C6F5)3)P[CH(CO2iPr)CH2(CO2iPr)]CH(CO2iPr), and (Nacnac)SnP (EtO2CCC(CO2Et))CO(B(C6F5)3), respectively. In contrast, the corresponding reaction of phenylacetylene gave the FLP-addition product (Nacnac)SnOC(P)C(Ph)CH(B(C6F5)3). Collectively, this reactivity demonstrates that the stannyl phosphaketene 1 can act as a synthon for P-analogues of ß-lactam derivatives.

Prevalence and risk factors for colonisation and infection with carbapenem-resistant Enterobacterales in intensive care units: A prospective multicentre study.

OBJECTIVES: This study aimed to investigate the prevalence and risk factors for carbapenem-resistant Enterobacterales colonisation/infection at admission and acquisition among patients admitted to the intensive care unit. RESEARCH METHODOLOGY/DESIGN: A prospective and multicentre study. SETTING: This study was conducted in 24 intensive care units in Anhui, China. MAIN OUTCOME MEASURES: Demographic and clinical data were collected, and rectal carbapenem-resistant Enterobacterales colonisation was detected by active screening. Multivariate logistic regression models were used to analyse factors associated with colonisation/infection with carbapenem-resistant Enterobacterales at admission and acquisition during the intensive care unit stay. RESULTS: There were 1133 intensive care unit patients included in this study. In total, 5.9% of patients with carbapenem-resistant Enterobacterales colonisation/infection at admission, and of which 56.7% were colonisations. Besides, 8.5% of patients acquired carbapenem-resistant Enterobacterales colonisation/infection during the intensive care stay, and of which 67.6% were colonisations. At admission, transfer from another hospital, admission to an intensive care unit within one year, colonisation/infection/epidemiological link with carbapenem-resistant Enterobacterales within one year, and exposure to any antibiotics within three months were risk factors for colonisation/infection with carbapenem-resistant Enterobacterales. During the intensive care stay, renal disease, an epidemiological link with carbapenem-resistant Enterobacterales, exposure to carbapenems and beta-lactams/beta-lactamase inhibitors, and intensive care stay of three weeks or longer were associated with acquisition. CONCLUSION: The prevalence of colonisation/infection with carbapenem-resistant Enterobacterales in intensive care units is of great concern and should be monitored systematically. Particularly for the 8.5% prevalence of carbapenem-resistant Enterobacterales acquisition during the intensive care stay needs enhanced infection prevention and control measures in these setting. Surveillance of colonisation/infection with carbapenem-resistant Enterobacterales at admission and during the patient's stay represents an early identification tool to prevent further transmission of carbapenem-resistant Enterobacterales. IMPLICATIONS FOR CLINICAL PRACTICE: Carbapenem-resistant Enterobacterales colonization screening at admission and during the patient's stay is an important tool to control carbapenem-resistant Enterobacterales spread in intensive care units.

Porous microneedle patch with sustained delivery of extracellular vesicles mitigates severe spinal cord injury.

The transplantation of mesenchymal stem cells-derived secretome, particularly extracellular vesicles is a promising therapy to suppress spinal cord injury-triggered neuroinflammation. However, efficient delivery of extracellular vesicles to the injured spinal cord, with minimal damage, remains a challenge. Here we present a device for the delivery of extracellular vesicles to treat spinal cord injury. We show that the device incorporating mesenchymal stem cells and porous microneedles enables the delivery of extracellular vesicles. We demonstrate that topical application to the spinal cord lesion beneath the spinal dura, does not damage the lesion. We evaluate the efficacy of our device in a contusive spinal cord injury model and find that it reduces the cavity and scar tissue formation, promotes angiogenesis, and improves survival of nearby tissues and axons. Importantly, the sustained delivery of extracellular vesicles for at least 7 days results in significant functional recovery. Thus, our device provides an efficient and sustained extracellular vesicles delivery platform for spinal cord injury treatment.

Reactivity of frustrated Lewis pairs with BOC protected diazocarboxylates: FLP capture of diazene.

Reactions of (tBuO2CN)2 with FLPs are examined. B(C6F5)3 interacts with the carbonyl oxygen atoms inducing loss of CH2CMe2; however, in the presence of basic donors, the protons are intercepted affording the salts [Hbase]2 [((C6F5)3BO2CN)2] (base = tBu3P 1, NC5H2Ph32, HNC5H6Me43). In contrast, in the presence of (o-Tol)3P, a proton transfers to the diazo-N atom affording (o-Tol)3PN(CO2tBu)NHB(C6F5)34. Further addition of B(C6F5)3 to 4 prompts loss of olefin CH2CMe2 and CO2 affording (o-Tol)3PNHNHB(C6F5)35. The course of these reactions is examined by extensive DFT calculations. The nature of 5 is consistent with the FLP reduction of a diazene fragment.

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.

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.

Transient hydroboration and hydroalumination of activated azo-species: avenues to NBO and NAlO-heterobicycles.

Reactions of the boranes, BH(C6F5)2 or 9-BBN, with azodicarboxylates or an azodicarbonylamide provide facile access to NBO heterocyclic compounds. The products [(C6F5)2BOC(X)N]2 X = OEt 1, OiPr 2, OCH2CCl33, OCH2Ph 4, NC5H105) and [(9-BBN)OC(X)N]2 (X = OEt 6, OiPr 7, NC5H108) and [Ph2B)OC(OtBu)N]29 were prepared. In another variation, (nacnac)AlH2 (nacnac = (C6H3iPr2NC(Me))2CH) afforded the Al-heterobicycle [(nacnac)Al(H)OC(OEt)N]210. The mechanism for the formation of these products is proposed to involve transient hydroboration or hydroalumination of the NN double bond.

Structure and reactivity studies of the aluminum analogue of Piers' borane [HAl(C6F5)2]3.

The aluminum analogue of Piers' borane, [HAl(C6F5)2]31, is prepared on a gram-scale. Density functional theory (DFT) calculations reveal 1 has a higher fluoride ion affinity (FIA) than Piers' borane, while the Al-H moiety proved to be a strong hydride donor, reacting with alcohol and terminal alkyne to give the corresponding dehydrogenative products 3 and 4. Hydroalumination product 5 was prepared via reaction of 1 with aldehyde. In addition, 1 catalyzes the hydrosilylation of alkynes and alkenes.

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.

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.

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.

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.

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.

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.