The combined effect of handgrip strength and obesity phenotype on the risk of stroke in Chinese middle-aged and elderly: A cohort study.

OBJECTIVE: The aim of this study was to investigate the combined effect of handgrip strength (HGS) and obesity phenotype on the risk of stroke in Chinese middle-aged and elderly people. METHODS: The data was used from the China Health and Retirement Longitudinal Study (CHARLS). Middle-aged and older adults who participated in surveys between 2011 and 2018 were included in the study. They were divided into 4 different types of obesity phenotypes based on obesity and metabolic status: metabolically healthy non-overweight/obesity (MHNO), metabolically healthy overweight/obesity (MHO), metabolically abnormal non-overweight/obesity (MANO), and metabolically abnormal overweight/obesity (MAO). The HGS level was divided into low and high groups according to the median values. Cox proportional risk regression model was used to analyze the joint effect of HGS and obesity phenotype on the risk of stroke among participants. RESULTS: A total of 7904 participants aged 58.89±9.08 years were included in this study. After adjusting for potential confounders, high HGS&MHO (HR=1.86, 95 % CI=1.12-3.09), high HGS&MANO (HR=2.01, 95 %CI=1.42-2.86), high HGS&MAO (HR=2.01, 95 % CI=1.37-2.93), low HGS&MHNO (HR=1.57, 95 % CI=1.00-2.46), low HGS&MHO (HR=2.09, 95 % CI=1.29-3.38), low HGS&MANO (HR=2.02, 95 % CI=1.35-3.03), and low HGS&MAO (HR=2.48, 95 % CI=1.72-3.58) group had significantly higher risks of stroke than the high HGS&MHNO group. CONCLUSION: The coexistence of metabolically unhealthy and low HGS can synergistically increase the risk of stroke in Chinese middle-aged and elderly people.

Strong and Tough MXene Bridging-induced Conductive Nacre.

Nacre is a classic model, providing an inspiration for fabricating high-performance bulk nanocomposites with the two-dimensional platelets. However, the "brick" of nacre, aragonite platelet, is an ideal building block for making high-performance bulk nanocomposites. Herein, we demonstrated a strong and tough conductive nacre through reassembling aragonite platelets with bridged by MXene nanosheets and hydrogen bonding, not only providing high mechanical properties but also excellent electrical conductivity. The flexural strength and fracture toughness of the obtained conductive nacre reach ~ 282 MPa and ~ 6.3 MPa m1/2, which is 1.6 and 1.6 times higher than that of natural nacre, respectively. These properties are attributed to densification and high orientation degree of the conductive nacre, which is effectively induced by the combined interactions of hydrogen bonding and MXene nanosheets bridging. The crack propagations in conductive nacre are effectively inhibited through crack deflection with hydrogen bonding, and MXene nanosheets bridging between aragonite platelets. In addition, our conductive nacre also provides a self-monitoring function for structural damage and offers exceptional electromagnetic interference shielding performance. Our strategy of reassembling the aragonite platelets exfoliated from waste nacre into high-performance artificial nacre, provides an avenue for fabricating high-performance bulk nanocomposites through the sustainable reutilization of shell resources.

Healing Health Care Disparities: Development and Pilot Testing of a Virtual Reality Implicit Bias Training Module for Physicians in the Context of Black Maternal Health.

Grounded in communication models of cultural competence, this study reports on the development and testing of the first module in a larger virtual reality (VR) implicit bias training for physicians to help them better: (a) recognize implicit bias and its effects on communication, patients, and patient care; (b) identify their own implicit biases and exercise strategies for managing them; and (c) learn and practice communicating with BIPOC patients in a culture-centered manner that demonstrates respect and builds trust. Led by communication faculty, a large, interdisciplinary team of researchers, clinicians, and engineers developed the first module tested herein focused on training goal (a). Within the module, participants observe five scenes between patient Marilyn Hayes (a Black woman) and Dr. Richard Flynn (her obstetrician, a White man) during a postpartum visit. The interaction contains examples of implicit bias, and participants are asked to both identify and consider how implicit bias impacts communication, the patient, and patient care. The team recruited 30 medical students and resident physicians to participate in a lab-based study that included a pretest, a training experience of the module using a head-mounted VR display, and a posttest. Following the training, participants reported improved attitudes toward implicit bias instruction, greater importance of determining patients' beliefs and perspectives for history-taking, treatment, and providing quality health care; and greater communication efficacy. Participants' agreement with the importance of assessing patients' perspectives, opinions, and psychosocial and cultural contexts did not significantly change. Implications for medical education about cultural competency and implicit bias are discussed.

Association between adding salt in food and dementia in European descent: A mendelian randomization study.

BACKGROUND: High salt intake has been proposed as a risk factor for dementia. However, causal relationship between salt intake and dementia remains uncertain. PURPOSE: The aim of this study was to employ a mendelian randomization (MR) design to investigate the causal impact of salt intake on the risk of dementia. METHODS: Genome-wide association study (GWAS) data of exposures and outcomes (any dementia, cognitive performance, different types of dementia, Alzheimer's disease [AD], and Parkinson's disease) were obtained from the IEU database. MR estimates were generated though inverse-variance weighted model. MR-Egger, weighted median, and MR-Pleiotropy Residual Sum and Outlier (MR-PRESSO) method also used in our study. Sensitivity analyses included Cochran's Q test, MR-Egger intercept, MR-PRESSO global test and outlier test, leave-one-out analysis, and funnel plot assessment. RESULTS: Our MR analysis provided evidence of a causal association between high salt added to food and dementia (odds ratio [OR] = 1.73, 95% confidence interval [CI]: 1.21-2.49, and p = .003), dementia in AD (OR = 2.10, 95% CI: 1.15-3.83, and p = .015), and undefined dementia (OR = 2.61, 95% CI: 1.26-5.39, and p = .009). Higher salt added was also associated with increased risk of AD (OR = 1.80, 95% CI: 1.12-2.87, and p = .014) and lower cognitive performance (ß = -.133, 95% CI: -.229 to -.038, and p = .006). CONCLUSION: This study provides evidence suggesting that high salt intake is causally associated with an increased risk of developing dementia, including AD and undefined dementia, highlighting the potential importance of reducing salt consumption as a preventive measure.

Osthole ameliorates early diabetic kidney damage by suppressing oxidative stress, inflammation and inhibiting TGF-ß1/Smads signaling pathway.

BACKGROUND: Osthole is a natural active ingredient extracted from the traditional Chinese medicine Cnidium monnieri. It has been demonstrated to have anti-inflammatory, anti-fibrotic, and anti-hyperglycemic properties. However, its effect on diabetic kidney disease (DKD) remains uncertain. This study aims to assess the preventive and therapeutic effects of osthole on DKD and investigate its underlying mechanisms. METHODS: A streptozotocin/high-fat and high-sucrose diet induced Type 2 diabetic rat model was established. Metformin served as the positive drug control. Diabetic rats were treated with metformin or three different doses of osthole for 8 weeks. Throughout the treatment period, the progression of DKD was assessed by monitoring increases in urinary protein, serum creatinine, urea nitrogen, and uric acid, along with scrutinizing kidney pathology. Enzyme-linked immunosorbent assay (ELISA) was employed to detect inflammatory factors and oxidative stress levels. At the same time, immunohistochemical staining was utilized to evaluate changes in alpha-smooth muscle actin, fibronectin, E-cadherin, and apoptosis. The alterations in TGF-ß1/Smads signaling pathway were ascertained through western blot and immunofluorescence. Furthermore, we constructed a high glucose-stimulated HBZY-1 cells model to uncover its molecular protective mechanism. RESULTS: Osthole significantly reduced fasting blood glucose, insulin resistance, serum creatinine, uric acid, blood urea nitrogen, urinary protein excretion, and glomerular mesangial matrix deposition in diabetic rats. Additionally, significant improvements were observed in inflammation, oxidative stress, apoptosis, and fibrosis levels. The increase of ROS, apoptosis and hypertrophy in HBZY-1 cells induced by high glucose was reduced by osthole. Immunofluorescence and western blot results demonstrated that osthole down-regulated the TGF-ß1/Smads signaling pathway and related protein expression. CONCLUSION: Our findings indicate that osthole exhibits potential preventive and therapeutic effects on DKD. It deserves further investigation as a promising drug for preventing and treating DKD.

Long COVID outcomes following omicron wave in non-hospital population.

Background: The persistence of symptoms or the development of new symptoms following a diagnosis of SARS-CoV-2 has given rise to a multifaceted clinical condition referred to as "long COVID" (LC). The understanding of LC among China's non-hospitalized population continues to be insufficient. This investigation was designed to evaluate the protracted consequences amongst this demographic, as well as to identify the associated risk factors. Methods: This research constitutes a prospective cohort study focusing on non-hospitalized individuals, aged between 18 and 59, who have been positively diagnosed with COVID-19. Each participant was subjected to a sequence of questionnaire-based surveys, designed to evaluate symptoms as well as the status of depression and anxiety. A logistic regression model, adjusted for multiple variables, was employed to scrutinize the correlation between demographic elements, lifestyle attributes, and health-related risk factors in relation to conditions and symptoms post COVID-19 infection. Results: A total of 706 individuals participated in the 3 months follow-up, with 620 continuing on to the 6 months follow-up. The median age was 35 (28, 43) years, and 597 (85%) are female. Upon follow-up, Compared with patients without LC, patients with LC have a higher proportion of females (420 (87%) vs. 177 (79%); p = 0.010), were older (35 (29, 44) years vs. 33 (27, 41) years; p = 0.010) and have more comorbidities. Out of all participants, 483 (68.4%) reported experiencing at least one symptom at the 3 months mark, while 49.7% reported symptoms persisting at the 6 months mark. At the 3 months follow-up, the most prevalent persistent symptoms were cough (46%), fatigue (38%), and shortness of breath (34%). By the 6 months follow-up, fatigue (25%), shortness of breath (22%), and sleep disorders (16%) were the most commonly reported symptoms. Anxiety and depression were consistently reported as prevalent symptoms throughout the follow-up period. Most patient symptoms fade over time, with the quickest decreases observed in cough (from 46 to 9%), expectoration (from 26 to 6.3%), smell disorder (from 16 to 3.9%), and taste disorder (from 18 to 3.5%). Male and those possessing advanced educational qualifications exhibit a decreased susceptibility to the sustained incidence of coughing. Conversely, older age and the presence of comorbidities were identified as risk factors for persistent fatigue and shortness of breath. Conclusion: In the after of COVID-19, it has been observed that the majority of patient symptoms tend to decrease over time. The primary residual symptoms noticed after a 6 month follow-up were fatigue, dyspnea, and sleep disturbances. However, it's noteworthy that the risk factors associated with these symptoms exhibit subtle variations. Furthermore, psychological sequelae, namely depression and anxiety, are frequently reported among COVID-19 survivors.

Sex-specific expression of distinct serotonin receptors mediates stress vulnerability of adult hippocampal neural stem cells in mice.

Women are more vulnerable to stress and have a higher likelihood of developing mood disorders. The serotonin (5HT) system has been highly implicated in stress response and mood regulation. However, sex-dependent mechanisms underlying serotonergic regulation of stress vulnerability remain poorly understood. Here, we report that adult hippocampal neural stem cells (NSCs) of the Ascl1 lineage (Ascl1-NSCs) in female mice express functional 5HT1A receptors (5HT1ARs), and selective deletion of 5HT1ARs in Ascl1-NSCs decreases the Ascl1-NSC pool only in females. Mechanistically, 5HT1AR deletion in Ascl1-NSCs of females leads to 5HT-induced depolarization mediated by upregulation of 5HT7Rs. Furthermore, repeated restraint stress (RRS) impairs Ascl1-NSC maintenance through a 5HT1AR-mediated mechanism. By contrast, Ascl1-NSCs in males express 5HT7R receptors (5HT7Rs) that are downregulated by RRS, thus maintaining the Ascl1-NSC pool. These findings suggest that sex-specific expression of distinct 5HTRs and their differential interactions with stress may underlie sex differences in stress vulnerability.

Identification of Mycobacterium tuberculosis Resistance to Common Antibiotics: An Overview of Current Methods and Techniques.

Multidrug-resistant tuberculosis (MDR-TB) is an essential cause of tuberculosis treatment failure and death of tuberculosis patients. The rapid and reliable profiling of Mycobacterium tuberculosis (MTB) drug resistance in the early stage is a critical research area for public health. Then, most traditional approaches for detecting MTB are time-consuming and costly, leading to the inappropriate therapeutic schedule resting on the ambiguous information of MTB drug resistance, increasing patient economic burden, morbidity, and mortality. Therefore, novel diagnosis methods are frequently required to meet the emerging challenges of MTB drug resistance distinguish. Considering the difficulty in treating MDR-TB, it is urgently required for the development of rapid and accurate methods in the identification of drug resistance profiles of MTB in clinical diagnosis. This review discussed recent advances in MTB drug resistance detection, focusing on developing emerging approaches and their applications in tangled clinical situations. In particular, a brief overview of antibiotic resistance to MTB was present, referred to as intrinsic bacterial resistance, consisting of cell wall barriers and efflux pumping action and acquired resistance caused by genetic mutations. Then, different drug susceptibility test (DST) methods were described, including phenotype DST, genotype DST and novel DST methods. The phenotype DST includes nitrate reductase assay, RocheTM solid ratio method, and liquid culture method and genotype DST includes fluorescent PCR, GeneXpert, PCR reverse dot hybridization, ddPCR, next-generation sequencing and gene chips. Then, novel DST methods were described, including metabolism testing, cell-free DNA probe, CRISPR assay, and spectral analysis technique. The limitations, challenges, and perspectives of different techniques for drug resistance are also discussed. These methods significantly improve the detection sensitivity and accuracy of multidrug-resistant tuberculosis (MRT) and can effectively curb the incidence of drug-resistant tuberculosis and accelerate the process of tuberculosis eradication.

Controllable 1,3-Bis-Functionalization of 2-Nitroglycals with High Regioselectivity and Stereoselectivity Enabled by a H-Bond Catalyst.

The selective modification of carbohydrates is significant for producing their unnatural analogues for drug discovery. C1-functionalization (glycosylation) and C1,C2-difunctionalization of carbohydrates have been well developed. In contrast, C3-functionalization or C1,C3-difunctionalization of carbohydrates remains rare. Herein, we report such processes that efficiently and stereoselectively modify carbohydrates. Specifically, we found that trifluoroethanol (TFE) could promote 1,3-bis-indolylation/pyrrolylation of 2-nitroglycals generated carbohydrate derivatives in up to 93% yield at room temperature; slightly reducing the temperature could install two different indoles at the C1- and C3-positions. Switching TFE to a bifunctional amino thiourea catalyst leads to the generation of C3 monosubstituted carbohydrates, which could also be used to construct 1,3-di-C-functionalized carbohydrates. This approach produced a range of challenging sugar derivatives (over 80 examples) with controllable and high stereoselectivity (single isomer for over 90% of the examples). The potential applications of the reaction were demonstrated by a set of transformations including the synthesis of bridged large-ring molecules and gram scale reactions. Biological activities evaluation demonstrated that three compounds exhibit a potent inhibitory effect on human cancer cells T24, HCT116, AGS, and MKN-45 with IC50 ranged from 0.695 to 3.548 µM.

The Constructing of the Oxide Phase Diagram for Fluoride Adsorption on La-Fe-Al: A Collaborative Study of Density Functional Calculation and Experimentation.

In recent years, fluoride pollution in water is a problem that has attracted much attention from researchers. The removal of fluoride-containing wastewater by adsorption with metal oxide as an adsorbent is the most common treatment method. Based on this, the effect of the doping ratio of La2O3, Fe2O3, and Al2O3 on the fluoride-removal performance was discussed by constructing a phase diagram. In this study, the adsorption mechanism of nanocrystalline lanthanum oxide terpolymer was investigated by density functional theory calculation and experiment. The optimal pH condition selected in the experiment was three, and the adsorption kinetics of fluoride ions were more consistent with the quasi-second-order kinetic model. The adsorption thermodynamics was more consistent with the Langmuir model. When the La-Fe-Al ternary composite oxides achieved the optimal adsorption efficiency for fluoride ions, the mass synthesis ratio was Al2O3:(Fe2O3:La2O3 = 1:2) = 1:100, resulting in a fluoride ion removal rate of up to 99.78%. Density functional calculations revealed that the La-Fe-Al ternary composite oxides had three important adsorption sites for La, Fe, and Al. Among them, the adsorption capacity for HF was Fe2O3 > La2O3 > Al2O3, and for F- was La2O3 > Al2O3 > Fe2O3. This provided good guidance for designing adsorbents to remove fluoride.

Development and Recent Progress of Hoses for Cryogenic Liquid Transportation.

Recently, the application of cryogenic hoses in the field of cryogenic media has become a hot topic, especially in the industry of offshore liquefied natural gas and aerospace field. However, the structure of cryogenic hoses is complex, and reasonable structural properties are required due to the harsh working conditions. There is still plenty of scope for further development to improve the performance in all aspects. In this paper, the current development status of cryogenic hoses for liquefied natural gas (LNG) transportation is reviewed first, including the types, manufacturers, structural forms, performance, and key technical challenges. And then, the recent progress and prospect of cryogenic hoses for cryogenic liquid transportation (such as LNG and liquid oxygen) are summarized, including structure design, low-temperature resistant polymers, liquid oxygen compatible polymers, and leakage monitoring technologies. This paper provides a comprehensive overview of the research development and application of cryogenic hoses. Moreover, future research directions have been proposed to facilitate its practical applications in aerospace.

Potential electron acceptors for ammonium oxidation in wastewater treatment system under anoxic condition: A review.

Anaerobic ammonium oxidation has been considered as an environmental-friendly and energy-efficient biological nitrogen removal (BNR) technology. Recently, new reaction pathway for ammonium oxidation under anaerobic condition had been discovered. In addition to nitrite, iron trivalent, sulfate, manganese and electrons from electrode might be potential electron acceptors for ammonium oxidation, which can be coupled to traditional BNR process for wastewater treatment. In this paper, the pathway and mechanism for ammonium oxidation with various electron acceptors under anaerobic condition is studied comprehensively, and the research progress of potentially functional microbes is summarized. The potential application of various electron acceptors for ammonium oxidation in wastewater is addressed, and the N2O emission during nitrogen removal is also discussed, which was important greenhouse gas for global climate change. The problems remained unclear for ammonium oxidation by multi-electron acceptors and potential interactions are also discussed in this review.

Differential depletion of GluN2A induces heterogeneous schizophrenia-related phenotypes in mice.

BACKGROUND: Schizophrenia, a debilitating psychiatric disorder, displays considerable interindividual variation in clinical presentations. The ongoing debate revolves around whether this heterogeneity signifies a continuum of severity linked to a singular causative factor or a collection of distinct subtypes with unique origins. Within the realm of schizophrenia, the functional impairment of GluN2A, a subtype of the NMDA receptor, has been associated with an elevated risk. Despite GluN2A's expression across various neuronal types throughout the brain, its specific contributions to schizophrenia and its involvement in particular cell types or brain regions remain unexplored. METHODS: We generated age-specific, cell type-specific or brain region-specific conditional knockout mice targeting GluN2A and conducted a comprehensive analysis using tests measuring phenotypes relevant to schizophrenia. FINDINGS: Through the induction of germline ablation of GluN2A, we observed the emergence of numerous schizophrenia-associated abnormalities in adult mice. Intriguingly, GluN2A knockout performed at different ages, in specific cell types and within distinct brain regions, we observed overlapping yet distinct schizophrenia-related phenotypes in mice. INTERPRETATION: Our interpretation suggests that the dysfunction of GluN2A is sufficient to evoke heterogeneous manifestations associated with schizophrenia, indicating that GluN2A stands as a prominent risk factor and a potential therapeutic target for schizophrenia. FUNDING: This project received support from the Shanghai Municipal Science and Technology Major Project (Grant No. 2019SHZDZX02) awarded to Y.C. and the Natural Science Foundation of Shanghai (Grant No. 19ZR1468600 and 201409003800) awarded to G.Y.

Anesthetic Sevoflurane Induces Enlargement of Dendritic Spine Heads in Mouse Neurons via Tau-Dependent Mechanisms.

BACKGROUND: Sevoflurane induces neuronal dysfunction and cognitive impairment. However, the underlying mechanism remains largely to be determined. Tau, cyclophilin D, and dendritic spine contribute to cognitive function. But whether changes in dendritic spines are involved in the effects of sevoflurane and the potential association with tau and cyclophilin D is not clear. METHODS: We harvested hippocampal neurons from wild-type mice, tau knockout mice, and cyclophilin D knockout mice. We treated these neurons with sevoflurane at day in vitro 7 and measured the diameter of dendritic spine head and the number of dendritic spines. Moreover, we determined the effects of sevoflurane on the expression of excitatory amino acid transporter 3 (EAAT3), extracellular glutamate levels, and miniature excitatory postsynaptic currents (mEPSCs). Finally, we used lithium, cyclosporine A, and overexpression of EAAT3 in the interaction studies. RESULTS: Sevoflurane-induced tau phosphgorylation increased the diameter of dendritic spine head and decreased the number of dendritic spines in neurons harvested from wild-type and cyclophilin D knockout mice, but not tau knockout mice. Sevoflurane decreased the expression of EAAT3, increased extracellular glutamate levels, and decreased the frequency of mEPSCs in the neurons. Overexpression of EAAT3 mitigated the effects of sevoflurane on dendritic spines. Lithium, but not cyclosporine A, attenuated the effects of sevoflurane on dendritic spines. Lithium also inhibited the effects of sevoflurane on EAAT3 expression and mEPSCs. CONCLUSIONS: These data suggest that sevoflurane induces a tau phosphorylation-dependent demtrimental effect on dendritic spine via decreasing EAAT3 expression and increasing extracellular glutamate levels, leading to neuronal dysfunction.

Iron complex regulated synergistic effect between the current and peroxymonosulfate enhanced ultrafast oxidation of perfluorooctanoic acid via free radical dominant electrochemical reaction.

Iron complex regulated electrochemical reaction was triggered for revealing the reaction mechanism, degradation pathway, and applied potential of perfluorooctanoic acid (PFOA). The increased PMS concentrations, electrode spacing, and current density significantly enhanced PFOA elimination, with current density exhibiting a relatively strong interdependency to PFOA complete mineralization. The synergy between PMS and electrochemical reactions greatly accelerated PFOA decomposition by promoting the generation of key reaction sites, such as those for PMS activation and electrochemical processes, under various conditions. Furthermore, density functional theory calculations confirmed that the reciprocal transformation of Fe2+ and Fe3+ complexes was feasible under the electrochemical effect, further promoting the generation of active sites. The developed electrochemical oxidation with PMS reaction (EO/PMS) system can rapidly decompose and mineralize PFOA while maintaining strong tolerance to changing water matrices and organic and inorganic ions. Overall, it holds promise for use in treating and purifying wastewater containing PFOA.

Ferric and sulfate coupled ammonium oxidation enhanced nitrogen removal in two-stage partial nitrification - Anammox/denitrification process for food waste liquid digestate treatment.

Liquid digestate of food waste is an ammonium-, ferric- and sulfate-laden leachate produced during digestate dewatering, where the carbon source is insufficient for nitrogen removal. A two-stage partial nitrification-anammox/denitrification process was established for nitrogen removal of liquid digestate without pre-treatment (>300 d), through which nitrogen (95 %), biodegradable organics (100 %), sulfate (78 %) and iron (100 %) were efficiently removed. Additional ammonium conversion (20 %N) might be coupled with ferric and sulfate reduction, while produced nitrite could be further converted to di-nitrogen gas through anammox (75 %) and denitrification (25 %). Notably, since increasingly contribution of hydroxylamine producing nitrous oxide, and up-regulated expression of electron transfer and cytochrome c protein, the enhanced ammonium oxidation was probably conducted through extracellular polymeric substances-mediated electron transfer between sulfate/ferric-reducers and aerobic ammonium oxidizers. Thus, the established partial nitrification-anammox/denitrification process might be a cost-efficient nitrogen removal technology for liquid digestate, benefitting to domestic waste recycling and carbon neutralization.

Prediction of Human Pharmacokinetics of E0703, a Novel Radioprotective Agent, Using Physiologically Based Pharmacokinetic Modeling and an Interspecies Extrapolation Approach.

E0703, a new steroidal compound optimized from estradiol, significantly increased cell proliferation and the survival rate of KM mice and beagles after ionizing radiation. In this study, we characterize its preclinical pharmacokinetics (PK) and predict its human PK using a physiologically based pharmacokinetic (PBPK) model. The preclinical PK of E0703 was studied in mice and Rhesus monkeys. Asian human clearance (CL) values for E0703 were predicted from various allometric methods. The human PK profiles of E0703 (30 mg) were predicted by the PBPK model in Gastro Plus software 9.8 (SimulationsPlus, Lancaster, CA, USA). Furthermore, tissue distribution and the human PK profiles of different administration dosages and forms were predicted. The 0.002 L/h of CL and 0.005 L of Vss in mice were calculated and optimized from observed PK data. The plasma exposure of E0703 was availably predicted by the CL using the simple allometry (SA) method. The plasma concentration-time profiles of other dosages (20 and 40 mg) and two oral administrations (30 mg) were well-fitted to the observed values. In addition, the PK profile of target organs for E0703 exhibited a higher peak concentration (Cmax) and AUC than plasma. The developed E0703-PBPK model, which is precisely applicable to multiple species, benefits from further clinical development to predict PK in humans.

Molecular mechanism of endophytic bacteria DX120E regulating polyamine metabolism and promoting plant growth in sugarcane.

Introduction: Sugarcane endophytic nitrogen-fixing bacterium Klebsiella variícola DX120E displayed broad impact on growth, but the exact biological mechanism, especially polyamines (PAs) role, is still meager. Methods: To reveal this relationship, the content of polyamine oxidase (PAO), PAs, reactive oxygen species (ROS)-scavenging antioxidative enzymes, phytohormones, 1-aminocyclopropane-1-carboxylic synthase (ACS), chlorophyll content, and biomass were determined in sugarcane incubated with the DX120E strain. In addition, expression levels of the genes associated with polyamine metabolism were measured by transcriptomic analysis. Results: Genomic analysis of Klebsiella variícola DX120E revealed that 39 genes were involved in polyamine metabolism, transport, and the strain secrete PAs in vitro. Following a 7-day inoculation period, DX120E stimulated an increase in the polyamine oxidase (PAO) enzyme in sugarcane leaves, however, the overall PAs content was reduced. At 15 days, the levels of PAs, ROS-scavenging antioxidative enzymes, and phytohormones showed an upward trend, especially spermidine (Spd), putrescine (Put), catalase (CAT), auxin (IAA), gibberellin (GA), and ACS showed a significant up-regulation. The GO and KEGG enrichment analysis found a total of 73 differentially expressed genes, involving in the cell wall (9), stimulus response (13), peroxidase activity (33), hormone (14) and polyamine metabolism (4). Discussion: This study demonstrated that endophytic nitrogen-fixing bacteria stimulated polyamine metabolism and phytohormones production in sugarcane plant tissues, resulting in enhanced growth. Dual RNA-seq analyses provided insight into the early-stage interaction between sugarcane seedlings and endophytic bacteria at the transcriptional level. It showed how diverse metabolic processes selectively use distinct molecules to complete the cell functions under present circumstances.

Dynamic monitoring of neutrophil/lymphocyte ratio, APACHE II score, and SOFA score predict prognosis and drug resistance in patients with Acinetobacter baumannii-calcoaceticus complex bloodstream infection: a single-center retrospective study.

Objective: This study aimed to evaluate the clinical value of dynamic monitoring of neutrophil/lymphocyte ratio (NLR), APACHE II (Acute Physiology and Chronic Health Evaluation II) score, and Sequential Organ Failure Assessment (SOFA) score in predicting 28-day prognosis and drug resistance in patients with bloodstream infection with Acinetobacter baumannii-calcoaceticus complex (Abc complex). Patients and methods: In this research, individuals admitted to Tianjin Medical University General Hospital from January 2017 to March 2023 with bloodstream infections and a minimum of one Abc complex positive blood culture were chosen. The risk factors for the 28-day prognosis and drug resistance were analyzed using logistic regression. The NLR, APACHE II score, and SOFA score were evaluated for predicting 28-day prognosis and drug resistance using an ROC curve analysis. The data were analyzed using R Studio to find correlations and conduct survival analysis with the Kaplan-Meier method. Results: The final statistical analysis included a total of 129 patients with bloodstream infections caused by Abc complex. Independent risk factors predicting mortality within 28 days were identified as follows: the SOFA score and APACHE II scores at 24 h, and APACHE II scores at 72 h after the onset of blood infection (p < 0.05). NLR, SOFA score, and APACHE II score did not predict drug resistance. Patients with Carbapenem-resistant Acinetobacter baumannii-calcoaceticus complex (CRAB) had shorter survival times than those with carbapenem-sensitive strains (40.77 days vs. 47.65 days, respectively, p = 0.0032). Conclusion: The prognosis of Abc complex bloodstream infection is affected by both SOFA and APACHE II scores. Both scoring systems have similar prognostic values at different time points after infection, but for computational convenience, it is recommended to use the SOFA score. NLR exhibits limited effectiveness in predicting mortality within 28 days. Carbapenem-resistant individuals with Abc complex experience significantly reduced survival time. None of the three factors-SOFA score, APACHE II score, and NLR-can early predict the occurrence of CRAB infections effectively.