A rational designed multi-epitope vaccine elicited robust protective efficacy against Klebsiella pneumoniae lung infection.

BACKGROUND: The emergence of drug-resistant strains of Klebsiella pneumoniae (K. pneumoniae) has become a significant challenge in the field of infectious diseases, posing an urgent need for the development of highly protective vaccines against this pathogen. METHODS AND RESULTS: In this study, we identified three immunogenic extracellular loops based on the structure of five candidate antigens using sera from K. pneumoniae infected mice. The sequences of these loops were linked to the C-terminal of an alpha-hemolysin mutant (mHla) from Staphylococcus aureus to generate a heptamer, termed mHla-EpiVac. In vivo studies confirmed that fusion with mHla significantly augmented the immunogenicity of EpiVac, and it elicited both humoral and cellular immune responses in mice, which could be further enhanced by formulation with aluminum adjuvant. Furthermore, immunization with mHla-EpiVac demonstrated enhanced protective efficacy against K. pneumoniae channeling compared to EpiVac alone, resulting in reduced bacterial burden, secretion of inflammatory factors, histopathology and lung injury. Moreover, mHla fusion facilitated antigen uptake by mouse bone marrow-derived cells (BMDCs) and provided sustained activation of these cells. CONCLUSIONS: These findings suggest that mHla-EpiVac is a promising vaccine candidate against K. pneumoniae, and further validate the potential of mHla as a versatile carrier protein and adjuvant for antigen design.

Photochemical evolution of the molecular composition of dissolved organic carbon and dissolved brown carbon from wood smoldering.

Recently, extreme wildfires occur frequently around the world and emit substantial brown carbon (BrC) into the atmosphere, whereas the molecular compositions and photochemical evolution of BrC remain poorly understood. In this work, primary smoke aerosols were generated from wood smoldering, and secondary smoke aerosols were formed by the OH radical photooxidation in an oxidation flow reactor, where both primary and secondary smoke samples were collected on filters. After solvent extraction of filter samples, the molecular composition of dissolved organic carbon (DOC) was determined by Fourier transform ion cyclotron resonance mass spectrometry (FTICR MS). The molecular composition of dissolved BrC was obtained based on the constraints of DOC formulae. The proportion of dissolved BrC fractions accounted for approximately 1/3-1/2 molecular formulae of DOC. The molecular characteristics of dissolved BrC showed higher levels of carbon oxidation state, double bond equivalents, and modified aromaticity index than those of DOC, indicating that dissolved BrC fractions were a class of organic structures with relatively higher oxidation state, unsaturated and aromatic degree in DOC fractions. The comparative analysis suggested that aliphatic and olefinic structures dominated DOC fractions (contributing to 70.1%-76.9%), while olefinic, aromatic, and condensed aromatic structures dominated dissolved BrC fractions (contributing to 97.5%-99.9%). It is worth noting that dissolved BrC fractions only contained carboxylic-rich alicyclic molecules (CRAMs)-like structures, unsaturated hydrocarbons, aromatic structures, and highly oxygenated compounds. CRAMs-like structures were the most abundant species in both DOC and dissolved BrC fractions. Nevertheless, the specific molecular characteristics for DOC and dissolved BrC fractions varied with subgroups after aging. The results highlight the similarities and differences in the molecular compositions and characteristics of DOC and dissolved BrC fractions with aging. This work will provide insights into understanding the molecular composition of DOC and dissolved BrC in smoke.

Binding Strengths and Orientations in CO2 Adsorption on Cationic Scandium Oxides: Governing Factor Revealed by a Combined Infrared Spectroscopy and Theoretical Study.

Carbon dioxide (CO2) adsorption is a critical step to curbing carbon emissions from fossil fuel combustion. Among various options, transition metal oxides have received extensive attention as promising CO2 adsorbents due to their affordability and sustainability for large-scale use. Here, the nature of binding interactions between CO2 molecules and cationic scandium oxides of different sizes, i.e., ScO+, Sc2O2+, and Sc3O4+, is investigated by mass-selective infrared photodissociation spectroscopy combined with quantum chemical calculations. The well-accepted electrostatic considerations failed to provide explanations for the trend in the binding strengths and variations in the binding orientations between CO2 and metal sites of cationic scandium oxides. The importance of orbital interactions in the driving forces for CO2 adsorption on cationic scandium oxides was revealed by energy decomposition analyses. A molecular surface property, known as the local electron attachment energy, is introduced to elucidate the binding affinity and orientation-specific reactivity of cationic scandium oxides upon the CO2 attachment. This study not only reveals the governing factor in the binding behaviors of CO2 adsorption on cationic scandium oxides but also serves as an archetype for predicting and rationalizing favorable binding sites and orientations in extended surface-adsorbate systems.

Online quantification of nicotine in e-cigarette aerosols by vacuum ultraviolet photoionization mass spectrometry.

The growing popularity of e-cigarettes and the associated risks of nicotine addiction present a new challenge to global public health security. Measuring the nicotine levels in e-cigarette aerosols is essential to assess the safety of e-cigarettes. In this study, a rapid in situ method was developed for online quantification of nicotine in e-cigarette aerosols by using a homemade vacuum ultraviolet photoionization aerosol mass spectrometer (VUV-AMS). E-cigarette liquids with different nicotine concentrations were prepared to generate aerosols containing different levels of nicotine, which were employed as the calibration sources for nicotine quantification by VUV-AMS. The results showed that the mass concentration of nicotine in e-cigarette aerosols has a good linear relationship with its signal intensity in the mass spectrum, and the limits of detection and quantitation of nicotine by VUV-AMS were found to be 2.0 and 6.2 µg per puff respectively. Then the online method was utilized to measure five commercial e-cigarettes, and their nicotine yields were determined to be between 31 and 188 µg per puff with the nicotine fluxes from 7.7 to 70 µg s-1, agreeing with the results of the gas chromatography with a flame ionization detector (GC-FID). This study demonstrated the feasibility and advantages of VUV-AMS for quick quantification of nicotine in e-cigarette aerosols within seconds.

CD39 expression defines exhausted CD4+ T cells associated with poor survival and immune evasion in human gastric cancer.

Objectives: CD4+ T cell helper and regulatory function in human cancers has been well characterised. However, the definition of tumor-infiltrating CD4+ T cell exhaustion and how it contributes to the immune response and disease progression in human gastric cancer (GC) remain largely unknown. Methods: A total of 128 GC patients were enrolled in the study. The expression of CD39 and PD-1 on CD4+ T cells in the different samples was analysed by flow cytometry. GC-infiltrating CD4+ T cell subpopulations based on CD39 expression were phenotypically and functionally assessed. The role of CD39 in the immune response of GC-infiltrating T cells was investigated by inhibiting CD39 enzymatic activity. Results: In comparison with CD4+ T cells from the non-tumor tissues, significantly more GC-infiltrating CD4+ T cells expressed CD39. Most GC-infiltrating CD39+CD4+ T cells exhibited CD45RA-CCR7- effector-memory phenotype expressing more exhaustion-associated inhibitory molecules and transcription factors and produced less TNF-α, IFN-γ and cytolytic molecules than their CD39-CD4+ counterparts. Moreover, ex vivo inhibition of CD39 enzymatic activity enhanced their functional potential reflected by TNF-α and IFN-γ production. Finally, increased percentages of GC-infiltrating CD39+CD4+ T cells were positively associated with disease progression and patients' poorer overall survival. Conclusion: Our study demonstrates that CD39 expression defines GC-infiltrating CD4+ T cell exhaustion and their immunosuppressive function. Targeting CD39 may be a promising therapeutic strategy for treating GC patients.

Asymmetrically Coordinated Mn-S1 N3 Configuration Induces Localized Electric Field-Driven Peroxymonosulfate Activation for Remarkably Efficient Generation of 1 O2.

Singlet oxygen (1 O2 ) species generated in peroxymonosulfate (PMS)-based advanced oxidation processes offer opportunities to overcome the low efficiency and secondary pollution limitations of existing AOPs, but efficient production of 1 O2 via tuning the coordination environment of metal active sites remains challenging due to insufficient understanding of their catalytic mechanisms. Herein, an asymmetrical configuration characterized by a manganese single atom coordinated is established with one S atom and three N atoms (denoted as Mn-S1 N3 ), which offer a strong local electric field to promote the cleavage of O─H and S─O bonds, serving as the crucial driver of its high 1 O2 production. Strikingly, an enhanced the local electric field caused by the dynamic inter-transformation of the Mn coordination structure (Mn-S1 N3 ↔ Mn-N3 ) can further downshift the 1 O2 production energy barrier. Mn-S1 N3 demonstrates 100% selective product 1 O2 by activation of PMS at unprecedented utilization efficiency, and efficiently oxidize electron-rich pollutants. This work provides an atomic-level understanding of the catalytic selectivity and is expected to guide the design of smart 1 O2 -AOPs catalysts for more selective and efficient decontamination applications.

Mechanistic insights into chemical conditioning on transformation of dissolved organic matter and plant biostimulants production during sludge aerobic composting.

Inorganic coagulants (aluminum and iron salt) are widely used to improve sludge dewaterability, resulting in numerous residues in dewatered sludge. Composting refers to the controlled microbial process that converts organic wastes into fertilizer, and coagulant residues in dewatered sludge can affect subsequent compost efficiency and resource recycling, which remains unclear. This work investigated the effects of two typical metal salt coagulants (poly aluminum chloride [PAC] and poly ferric sulfate [PFS]) conditioning on sludge compost. Our results revealed that PAC conditioning inhibited composting with decreased peak temperature, microbial richness, enzymatic reaction intensities, and compost quality, associated with decreased pH and microbial toxicity of aluminum. Nevertheless, PFS conditioning selectively enriched Pseudoxanthomonas sp. and resulted in more fertile compost with increased peak temperature, enzymatic reaction intensities, and humification degree. Spectroscopy and mass difference analyses indicated that PFS conditioning enhanced reaction intensities of labile biopolymers at the thermophilic stage, mainly comprising hydrolyzation (H2O), dehydrogenation (-H2, -H4), oxidation (+O1H2), and other reactions (i.e., +CH2, C2H4O1, C2H6O1). Unlike the common composting process primarily conducts humification at the cooling stage, PFS conditioning changed the main occurrence stage to the thermophilic stage. Non-targeted metabolomics revealed that indole (a humification intermediate) is responsible for the increased humification degree and indoleacetic acid content in the PFS-conditioned compost, which then promoted compost quality. Plant growth experiments further confirmed that the dissolved organic matter (DOM) in PFS-conditioned compost produced the maximum plant biomass. This study provided molecular-level evidence that PFS conditioning can promote humification and compost fertility during sludge composting, enabling chemical conditioning optimization for sustainable management of sludge.

Fungal community shows more variations by season and particle size than bacteria.

The global concern regarding the health risk associated with airborne microorganisms has prompted research in this field. However, there is a lack of systematic investigation into the particle-size distribution of airborne bacterial and fungal communities associated with seasons, which determines where they are deposited in the human respiratory tract. To address this gap, we conducted a study in Nanchang, located in central China, where we collected both coarse and fine particles during summer and winter seasons. The results demonstrated that microbial community exhibited obvious seasonal and particle-size variations except bacterial community in fine particles. Certain taxa (e.g., Bacteroidales, Ktedonobacterales, Capnodiales) displayed either seasonal and/or particle-size preferences. Furthermore, airborne microorganisms in coarse particles were more sensitive to season and particle size compared to those in fine particles, with fungal community being more susceptible than bacterial community. The susceptibility can be attributed to their high vulnerability to air pollutants and meteorological conditions, primarily PM2.5 and PM10. Additionally, a greater relative abundance of pathogenic fungi was observed in fine particles, even though microbial diversity in coarse particles was noticeably higher than that in fine particles. Furthermore, some predominant pathogens such as Alternaria, Nigrospora, and Escherichia-Shigella not only had particle size and/or seasonal preferences, but also were strongly correlated with environmental factors. This study advances our understanding of atmospheric pathogenic microorganisms and highlights the fungal health threat.

KDELR2 promotes bone marrow mesenchymal stem cell osteogenic differentiation via GSK3ß/ß-catenin signaling pathway.

Nonunion is a challenging complication of fractures for the surgeon. Recently the Lys-Asp-Glu-Leu (KDEL) endoplasmic reticulum protein retention receptor 2 (KDELR2) has been found that involved in osteogenesis imperfecta. However, the exact mechanism is still unclear. In this study, we used lentivirus infection and mouse fracture model to investigate the role of KDELR2 in osteogenesis. Our results showed that KDELR2 knockdown inhibited the osteogenic differentiation of mBMSCs, whereas KDELR2 overexpression had the opposite effect. Furthermore, the levels of active-ß-catenin and phospho-GSK3ß (Ser9) were upregulated by KDELR2 overexpression and downregulated by KDELR2 knockdown. In the fracture model, mBMSCs overexpressing KDELR2 promoted healing. In conclusion, KDELR2 promotes the osteogenesis of mBMSCs by regulating the GSK3ß/ß-catenin signaling pathway.

Fractal analysis of left ventricular trabeculae in post-STEMI: from acute to chronic phase.

PURPOSE: The temporal evolution of ventricular trabecular complexity and its correlation with major adverse cardiovascular events (MACE) remain indeterminate in patients presenting with acute ST elevation myocardial infarction (STEMI). METHODS: This retrospective analysis enrolled patients undergoing primary percutaneous coronary intervention (pPCI) for acute STEMI, possessing cardiac magnetic resonance (CMR) data in the acute (within 7 days), subacute (1 month after pPCI), and chronic phases (6 months after pPCI) from January 2015 to January 2020 at the three participating sites. Fractal dimensions (FD) were measured for the global, infarct, and remote regions of left ventricular trabeculae during each phase. The potential association of FD with MACE was analyzed using multivariate Cox regression. RESULTS: Among the 200 analyzed patients (182 men; median age, 61 years; age range, 50-66 years), 37 (18.5%) encountered MACE during a median follow-up of 31.2 months. FD exhibited a gradual decrement (global FD at acute, subacute, and chronic phases: 1.253 ± 0.049, 1.239 ± 0.046, 1.230 ± 0.045, p < 0.0001), with a more pronounced decrease observed in patients subsequently experiencing MACE (p < 0.001). The global FD at the subacute phase correlated with MACE (hazard ratio 0.89 (0.82, 0.97), p = 0.01), and a global FD value below 1.26 was associated with a heightened risk. CONCLUSION: In patients post-STEMI, the global FD, serving as an indicator of left ventricular trabeculae complexity, independently demonstrated an association with subsequent major adverse cardiovascular events, beyond factors encompassing left ventricular ejection fraction, indexed left ventricular end-diastolic volume, infarct size, heart rate, NYHA class, and post-pPCI TIMI flow. CRITICAL RELEVANCE STATEMENT: In patients who have had an ST-segment elevation myocardial infarction, global fractal dimension, as a measure of left ventricular trabeculae complexity, provided independent association with subsequent major adverse cardiovascular event. KEY POINTS: • Global and regional FD decreased after STEMI, and more so in patients with subsequent MACE. • Lower global FD at the subacute phase and Δglobal FD from acute to subacute phase were associated with subsequent MACE besides clinical and CMR factors. • Global FD at the subacute phase independently correlated with MACE and global FD value below 1.26 was associated with higher risk.

Inhibitory effect of microplastics derived organic matters on humification reaction of organics in sewage sludge under alkali-hydrothermal treatment.

Alkali-hydrothermal treatment (AHT) of sewage sludge is often used to recover value-added dissolved organic matters (DOM) enriched with artificial humic acids (HA). Microplastics (MPs), as emerging contaminants in sewage sludge, can leach organic compounds (MP-DOM) during AHT, which potentially impact the characteristics of thermally treated sludge's DOM. This study employed spectroscopy and Fourier transform-ion cyclotron resonance mass spectrometry (FT-ICR-MS) to explore the impacts of MPs on DOM composition and transformation during AHT. The biological effects of DOM were also investigated by hydroponic experiments. The results showed that the leaching of MP-DOM led to a substantial increase in DOC content of DOM of thermally treated sludge. Conversely, the HA content significantly decreased in the presence of MPs, resulting in a decline of plant growth facilitation degree. FT-ICR-MS analysis revealed that the reduction in HA content was characterized by a notable decline in the abundance of O6-7 and N1-3O6-7 molecules. Reactomics results indicated that the leaching of MP-DOM inhibited the Maillard reaction but bolstered oxidation reactions. The inhibition of Maillard reaction, resulting in a decrease in crucial precursors (dicarbonyl compounds, ketoses, and deoxyglucosone), was responsible for the decrease of HA content. The primary mechanism responsible for inhibiting the Maillard reaction was the consumption of reactive amino reactants through two pathways. Firstly, the leaching of organic acids in MP-DOM caused decrease of sludge pH, leading to the protonation of amino groups. Secondly, the lipid-like compounds in MP-DOM underwent oxidation (-2H+O), producing fatty aldehydes that consumed the reactive amino reactants. These discoveries offer enhanced insights into the specific contribution of MPs to the composition, transformation, bioactivity of DOM during AHT process.

Photochemical Transformation of Dissolved Organic Matter in Surface Water Augmented the Formation of Disinfection Byproducts.

Sunlight may lead to changes in disinfection byproducts (DBPs) formation potentials of source water via transforming dissolved organic matter (DOM); however, the underlying mechanisms behind these changes remain unclear. This work systematically investigated the effect of photochemical transformation of DOM from reservoir water (DOMRe) and micropolluted river water (DOMRi) after 36 h of simulated sunlight irradiation (equivalent to one month under natural sunlight) on DBPs formation. Upon irradiation, high molecular weight (MW) and aromatic molecules tended to be mineralized or converted into low-MW and highly oxidized (O/C > 0.5) ones which might react with chlorine to generate high levels of DBPs, resulting in an elevation in the yields (µg DBP/mg C) of almost all the measured DBPs and the quantities of unknown DBPs in both DOM samples after chlorination. Additionally, DOMRi contained more aromatic molecules susceptible to photooxidation than DOMRe. Consequently, irradiated DOMRi exhibited a greater increase in the formation potentials of haloacetonitriles, halonitromethanes, and specific regulated DBPs, with nitrogenous DBPs being responsible for the overall rise in the calculated cytotoxicity following chlorination. This work emphasized the importance of a comprehensive removal of phototransformation products that may serve as DBPs precursors from source waters, especially from micropolluted source waters.

Regional distribution prevalence of heterotopic ossification in the elbow joint: a 3D study of patients after surgery for traumatic elbow injury.

BACKGROUND: Heterotopic ossification (HO) is a common complication after elbow fracture surgery and can lead to severe upper extremity disability. The radiographic localization of postoperative HO has been reported previously. However, there is no literature examining the distribution of postoperative HO at the three-dimensional (3D) level. This study aimed to investigate 1) the distribution characteristics of postoperative HO and 2) the possible risk factors affecting the severity of postoperative HO at a 3D level. METHODS: A retrospective review was conducted of patients who presented to our institution with HO secondary to elbow fracture between 13 January 2020 and 16 February 2023. Computed tomography scans of 56 elbows before elbow release surgery were reconstructed in 3D. HO was identified using density thresholds combined with manual identification and segmentation. The elbow joint and HO were divided into six regions according to three planes: the transepicondylar plane, the lateral ridge of the trochlear plane, and the radiocapitellar joint and coronoid facet plane. The differences in the volume of regional HO associated with different initial injuries were analyzed. RESULTS: Postoperative HO was predominantly present in the medial aspect of the capsule in 52 patients (93%), in the lateral aspect of the capsule in 45 patients (80%), in the medial supracondylar in 32 patients (57%), and in the lateral supracondylar, radial head, and ulnar region in the same number of 28 patients (50%). The median and interquartile range volume of total postoperative HO was 1683 (777-4894) mm3. The median and interquartile range volume of regional postoperative HO were: 584 (121-1454) mm3 at medial aspect of capsule, 207 (5-568) mm3 at lateral aspect of capsule, 25 (0-449) mm3 at medial supracondylar, 1 (0-288) at lateral supracondylar, 2 (0-478) at proximal radius and 7 (0-203) mm3 at the proximal ulna. In the subgroups with Injury Severity Score > or = 16, Gustilo-Anderson II, normal uric acid levels, elevated alkaline phosphatase, and body mass index > or = 24, the median HO volume exceeds that of the respective control groups. CONCLUSION: The medial aspect of the capsule was the area with the highest frequency and median volume of postoperative HO among all initial elbow injury types. Patients with higher Gustilo-Anderson grade, Injury Severity Score, alkaline phosphatase or Body Mass Index had higher median volume of postoperative HO.

A Respiratory Motion Prediction Method Based on LSTM-AE with Attention Mechanism for Spine Surgery.

Respiratory motion-induced vertebral movements can adversely impact intraoperative spine surgery, resulting in inaccurate positional information of the target region and unexpected damage during the operation. In this paper, we propose a novel deep learning architecture for respiratory motion prediction, which can adapt to different patients. The proposed method utilizes an LSTM-AE with attention mechanism network that can be trained using few-shot datasets during operation. To ensure real-time performance, a dimension reduction method based on the respiration-induced physical movement of spine vertebral bodies is introduced. The experiment collected data from prone-positioned patients under general anaesthesia to validate the prediction accuracy and time efficiency of the LSTM-AE-based motion prediction method. The experimental results demonstrate that the presented method (RMSE: 4.39%) outperforms other methods in terms of accuracy within a learning time of 2 min. The maximum predictive errors under the latency of 333 ms with respect to the x, y, and z axes of the optical camera system were 0.13, 0.07, and 0.10 mm, respectively, within a motion range of 2 mm.

Analysis of mandibular asymmetry in adolescent and adult patients with unilateral posterior crossbite on cone-beam computed tomography.

INTRODUCTION: This study aimed to evaluate mandibular asymmetry in unilateral posterior crossbite (UPXB) patients and compare the asymmetry between adolescents and adults with UPXB. METHODS: This study included and analyzed cone-beam computed tomography scans of 125 subjects. The subjects were divided into a UPXB group and a control group according to the presence or absence of UPXB, and each group included adolescent patients (aged 10-15 years) and adult patients (aged 20-40 years). Linear, angular, and volumetric measurements were obtained to evaluate the asymmetries of the mandibles. RESULTS: Both adolescent and adult patients in the UPXB group presented asymmetries in condylar unit length, ramal height, body length, and mediolateral ramal inclination (P <0.05). Adult patients with UPXB showed greater asymmetries than adolescents. Differences with condylar unit length, condylar unit width, ramal height, condylar unit volume, and hemimandibular volume were significantly greater in adult UPXB patients than adolescent UPXB patients (P <0.05). CONCLUSIONS: The worsening of mandibular asymmetries in UPXB adults suggests that asymmetry in UPXB patients may progress over time; therefore, early treatment should be considered for UPXB adolescent patients. Further studies are still needed to evaluate the effectiveness of early treatment.

Rapid start-up of an innovative pilot-scale staged PN/A continuous process for enhanced nitrogen removal from mature landfill leachate via robust NOB elimination and efficient biomass retention.

The start-up and stable operation of partial nitritation-anammox (PN/A) treatment of mature landfill leachate (MLL) still face challenges. This study developed an innovative staged pilot-scale PN/A system to enhance nitrogen removal from MLL. The staged process included a PN unit, an anammox upflow enhanced internal circulation biofilm (UEICB) reactor, and a post-biofilm unit. Rapid start-up of the continuous flow PN process (full-concentration MLL) was achieved within 35 days by controlling dissolved oxygen and leveraging free ammonia and free nitrous acid to selectively suppress nitrite-oxidizing bacteria (NOB). The UEICB was equipped with an annular flow agitator combined with the enhanced internal circulation device of the guide tube, which achieved an efficient enrichment of Candidatus Kuenenia in the biofilm (relative abundance of 33.4 %). The nitrogen removal alliance formed by the salt-tolerant anammox bacterium (Candidatus Kuenenia) and denitrifying bacteria (unclassified SBR1031 and Denitratisoma) achieved efficient nitrogen removal of UEICB (total nitrogen removal percentage: 90.8 %) and at the same time effective treatment of the refractory organic matter (ROM). The dual membrane process of UEICB fixed biofilm combined with post-biofilm is effective in sludge retention, and can stably control the effluent suspended solids (SS) at a level of less than 5 mg/L. The post-biofilm unit ensured that effluent total nitrogen (TN) remained below the 40 mg/L discharge standard (98.5 % removal efficiency). Compared with conventional nitrification-denitrification systems, the staged PN/A process substantially reduced oxygen consumption, sludge production, CO2 emissions and carbon consumption by 22.8 %, 67.1 %, 87.1 % and 87.1 %, respectively. The 195-day stable operation marks the effective implementation of the innovative pilot-scale PN/A process in treating actual MLL. This study provides insights into strategies for rapid start-up, robust NOB suppression, and anammox biomass retention to advance the application of PN/A in high-ammonia low-carbon wastewater.

Jasminoidin reduces ischemic stroke injury by regulating microglia polarization via PASK-EEF1A1 axis.

Jasminoidin (JAS) can alleviate ischemic stroke (IS) injury, but its molecular mechanism remains undefined. The polarization of microglia affects IS process. This research is powered to probe whether the molecular mechanism of JAS for IS treatment is coupled with microglia polarization. IS modeling in mice was accomplished by middle cerebral artery occlusion (MCAO) and model mice were injected with 25 and 50 mg/mL JAS, followed by determination of infarct volume, brain water content, and histological changes in mouse brains. The microglia modeling was performed by 1-h oxygen-glucose deprivation and 24-h reoxygenation. Oxygen-glucose deprivation/reoxygenation (OGD/R)-induced microglia were treated with JAS and transfected with Per-Arnt-Sim kinase (PASK)-overexpressing plasmid, subsequent to which cell viability and lactate dehydrogenase (LDH) level were determined. The mRNA or protein expressions of examined genes in microglia and brain tissues were detected by quantitative real-time polymerase chain reaction or western blot. MCAO-induced massive infarction, edema, and injury in mouse brain tissues, upregulated interleukin-1 beta (IL-1ß), FcγRIIB (CD32), tumor necrosis factor alpha (TNF-α), PASK, p-eukaryotic elongation factor 1A1 (EEF1A1), and p-EEF1A1/EEF1A1 levels, but downregulated mannose receptor 1 (CD206), arginase-1 (Arg-1) and interleukin-10 (IL-10), and EEF1A1 expressions, which was reversed by JAS. OGD/R treatment decreased microglial viability as well as expressions of CD206, Arg-1, IL-10, and EEF1A1, yet increased cytotoxicity and levels of IL-1ß, CD32, TNF-α, PASK, p-EEF1A1, and p-EEF1A1/EEF1A1, which was reversed by JAS. PASK overexpression reversed the effects of JAS on microglia. JAS reduces IS injury by regulating microglia polarization via PASK-EEF1A1 axis.

Carbon dioxide activation by discandium dioxide cations in the gas phase: a combined investigation of infrared photodissociation spectroscopy and DFT calculations.

We present a combined computational and experimental study of CO2 activation at the Sc2O2+ metal oxide ion center in the gas phase. Density functional theory calculations on the structures of [Sc2O2(CO2)n]+ (n = 1-4) ion-molecule complexes reveal a typical end-on binding motif as well as bidentate and tridentate carbonate-containing configurations. As the number of attached CO2 molecules increases, activated forms tend to dominate the isomeric populations. Distortion energies are unveiled to account for the conversion barriers from molecularly bound isomers to carbonate structures, and show a monotonically decreasing trend with successive CO2 ligand addition. The infrared photodissociation spectra of target ion-molecule complexes were recorded in the 2100-2500 cm-1 frequency region and interpreted by comparison with simulated IR spectra of low-lying isomers representing distinct configurations, demonstrating a high possibility of carbonate structure formation in current experiments.

Relationship between diabetic knowledge, attitudes and practices among patients with diabetes in China: a structural equation model.

OBJECTIVES: Whether the routine delivery of diabetes-related knowledge can change patients' attitudes and hence influence their self-management activities remains unknown in primary healthcare settings in China. Thus, this study aims to explore the complex transformation process between knowledge, attitude and practice (KAP) among patients with diabetes in a city in China. DESIGN: A cross-sectional study. SETTING: Yuhuan City, Zhejiang Province, China. PARTICIPANTS: A total of 803 patients with diabetes were invited to attend a questionnaire survey and 782 patients with type 2 diabetes completed the survey. The average age of participants was 58.47 years old, 48.21% of whom only attended primary school or below. PRIMARY AND SECONDARY OUTCOME MEASURES: A questionnaire based on existing scales and expert consultation was applied to assess patients' socio-demographic information (SI), disease progression risk and diabetes-related KAP. A structural equation model was built to analyse the relationships between patients' characteristics and KAP. RESULTS: No significant association was found between patients' knowledge and attitude (ß=0.01, p=0.43). Better knowledge and attitude were both found to be associated with better diet and physical activities (ß=0.58, p<0.001; ß=0.46, p=0.01). However, patients with a more positive attitude toward diabetic care showed worse foot care practice (ß=-0.13, p=0.02), while better knowledge was associated with better foot care practice (ß=0.29, p<0.001). In addition, patients with higher SI (ß=0.88, p<0.001) and/or disease progression risk (ß=0.42, p<0.001) tended to present higher levels of disease knowledge. CONCLUSIONS: While successful KAP transformation has been achieved in practice for diet and physical activities, there is a need to improve foot care practice. Health education should also prioritise the prevention, detection and care of diabetic foot. Also, appropriate methods should be adopted to deliver health education to vulnerable patients, such as the elderly, those living in rural areas, those with minimal education, the unemployed and low-income patients.

Diabetes knowledge predicts HbA1c levels of people with type 2 diabetes mellitus in rural China: a ten-month follow-up study.

Improving diabetes self-management (DSM) is facing real-world challenges among people with type 2 diabetes mellitus (T2DM) who have a low education level in resource-limited areas. This study aimed to investigate whether diabetes knowledge could predict glycemic levels in people with T2DM in rural China. This analytical cross-sectional study recruited 321 people with T2DM from eight villages by purposive sampling at baseline. After 10 months, 206 patients completed the follow-up survey and HbA1c tests, with a response rate of 64.17% (206/321). Multiple regression analysis was employed to explore the correlation between diabetes knowledge and HbA1c levels. The patient's diabetes knowledge was significantly negatively correlated with HbA1c levels before and after controlling for covariates in both hierarchical multiple regression and multiple logistic regression (p < 0.01). In addition, other influencing factors, including sex, age, marital status, employment status, income, and HbA1c levels at baseline, were also identified. Diabetes knowledge could predict HbA1c levels significantly among patients with low education levels in rural China. Therefore, interventions on improving diabetes knowledge need to be strengthened for patients in rural China so that they can improve their health outcomes and reduce the disease burden.