[Pathogen Distribution,Imaging Characteristics,and Establishment and Verification of Risk Prediction Model of Pulmonary Infection with Multi-drug Resistant Organism in Patients with Severe Craniocerebral Injury].

Objective To investigate the pathogen distribution,imaging characteristics,and risk factors of pulmonary infection with multi-drug resistant organism (MDRO) in patients with severe craniocerebral injury,and establish and verify the risk prediction model. Methods A total of 230 patients with severe craniocerebral injury complicated with pulmonary infection were collected retrospectively.According to the 7∶3 ratio,they were randomly assigned into a modeling group (161 patients) and a validation group (69 patients).The risk factors of MDRO pulmonary infection were predicted with the data of the modeling group for the establishment of the risk prediction model.The data of the validation group was used to validate the performance of the model. Results Among the 230 patients,68 patients developed MDRO pulmonary infection.The isolated drug-resistant bacteria mainly included multi-drug resistant Acinetobacter baumannii,multi-drug resistant Klebsiella pneumoniae,multi-drug resistant Pseudomonas aeruginosa,and methicillin-resistant Staphylococcus aureus,which accounted for 45.21%,23.29%,16.44%,and 15.07%,respectively.The imaging characteristics included pleural effusion,lung consolidation,and ground-glass shadow,which accounted for 72.06%,63.24%,and 45.59%,respectively.Multivariate Logistic regression analysis showed that the independent risk factors for MDRO pulmonary infection included age ≥60 years (P=0.003),history of diabetes (P=0.021),history of chronic obstructive pulmonary disease (P=0.038),mechanical ventilation ≥7 d (P=0.001),transfer from other hospitals (P=0.008),and coma (P=0.002).A risk scoring model was established with the ß value (rounded to the nearest integer) corresponding to each index in the regression equation.Specifically,the ß values of age ≥60 years,history of diabetes,history of chronic obstructive pulmonary disease,mechanical ventilation ≥7 d,transfer from other hospitals,and coma were 1,1,1,2,2,and 1,respectively (value ≥4 indicated a high-risk population).The areas under the receiver operating characteristic curve of the modeling group and validation group were 0.845 and 0.809,respectively. Conclusions Multi-drug resistant Acinetobacter baumannii is the most common pathogen of MDRO pulmonary infection in patients with severe craniocerebral injury.Pleural effusion,lung consolidation,and ground-glass shadow were the most common imaging characteristics.The established risk model has high discriminant validity in both the modeling group and the validation group.

Theoretical reflections on the structural polymorphism of the oxygen-evolving complex in the S2 state and the correlations to substrate water exchange and water oxidation mechanism in photosynthesis.

The structural polymorphism of the oxygen-evolving complex is of great significance to photosynthetic water oxidation. Employing density functional theory calculations, we have made further advisement on the interconversion mechanism of O5 transfer in the S2 state, mainly focusing on the potentiality of multi-state reactivity and spin transitions. Then, O5 protonation is proven impossible in S2 for irreversibility of the interconversion, which serves as an auxiliary judgment for the protonation state of O5 in S1. Besides, the structural polymorphism could also be archived by alternative mechanisms involving Mn3 ligand exchange, one of which with Mn3(III) makes sense to substrate water exchange in S2, although being irresponsible for the derivations of the observed EPR signals. During the water exchange, high-spin states would prevail to facilitate electron transfer between the ferromagnetically coupled Mn centers. In addition, water exchange in S1 could account for the closed-cubane structure as the initial form entering S2 at cryogenic temperatures. With regard to water oxidation, the structural flexibility and variability in both S2 and S3 guarantee smooth W2-O5 coupling in S4, according to the substrate assignments from water exchange kinetics. Within this theoretical framework, the new XFEL findings on S1-S3 can be readily rationalized. Finally, an alternative mechanistic scenario for OO bond formation with ·OH radical near O4 is presented, followed by water binding to the pivot Mn4(III) from O4 side during S4-S0. This may diversify the substrate sources combined with the Ca channel in water delivery for the forthcoming S-cycle.

The open-cubane oxo-oxyl coupling mechanism dominates photosynthetic oxygen evolution: a comprehensive DFT investigation on O-O bond formation in the S4 state.

The dioxygen formation mechanism of biological water oxidation in nature has long been the focus of argument; many diverse mechanistic hypotheses have been proposed. Based on a recent breakthrough in the resolution of the electronic and structural properties of the oxygen-evolving complex in the S3 state, our density functional theory (DFT) calculations reveal that the open-cubane oxo-oxyl coupling mechanism, whose substrates preferably originate from W2 and O5 in the S2 state, emerges as the best candidate for O-O bond formation in the S4 state. This is justified by the overwhelming energetic superiority of this mechanism over alternative mechanisms in both the isomeric open and closed-cubane forms of the Mn4CaO5 cluster; spin-dependent reactivity rooted in variable magnetic couplings was found to play an essential role. Importantly, this oxygen evolution mechanism is supported by the recent discovery of femtosecond X-ray free electron lasers (XFEL), and the origin of the observed structural changes from the S1 to S3 state has been analyzed. In this view, we corroborate the proposed water binding mechanism during S2-S3 transition and correlate the theoretical models with experimental findings from aspects of substrate selectivity according to water exchange kinetics. This theoretical consequence for native metalloenzymes may serve as a significant guide for improving the design and synthesis of biomimetic materials in the field of photocatalytic water splitting.

How does ammonia bind to the oxygen-evolving complex in the S2 state of photosynthetic water oxidation? Theoretical support and implications for the W1 substitution mechanism.

Ammonia as a water analogue can bind to the Mn4CaO5 cluster of the oxygen-evolving complex in concomitance with ligand substitution and underlying structural transformation. On account of current controversies of the binding site and the absence of the viewpoint of reactivity and mechanistic proofs, we have investigated three modes of NH3 binding based on our elaborations of the possible reaction mechanisms, in correspondence with experimental observation for the NH3-altered g ≈ 2.0 EPR multiline signal. Broken-symmetry density functional theory was employed to construct all the spin surfaces. As a result, we rule out the O5 substitution strategy owing to the impenetrable free energy barrier exceeding 30 kcal mol-1, and alternative routes to destroy the O5 bridge are also blocked. The W1 substitution mechanism is shown to be quite facile, with the barrier not above 11.4 kcal mol-1. For the Mn4 addition scheme, the 'redox switch mechanism' was not implemented by our model, and the effective ways found render 15-22 kcal mol-1 energetic disadvantage by contrast. Consequently, it is strongly in favor of the W1 substitution mechanism for its overwhelming superiority in reactivity, reaching a consensus with the new pulse EPR conclusion. Then, we point out that ammonia departure occurs in the S4' state, with the O-O bonding but unreleased molecular O2. In the meantime, we propose two alternative channels for water binding in the S0' state and expound the significance to substrate selectivity. Ultimately, implications for the mechanism of O-O bond formation are discussed and all the remaining options are listed for future explorations.