Stable Lithium Oxygen Batteries Enabled by Solvent-diluent Interaction in N,N-dimethylacetamide-based Electrolytes.

In the pursuit of next-generation ultrahigh-energy-density Li-O2 batteries, it is imperative to develop an electrolyte with stability against the strong oxidation environments. N,N-dimethylacetamide (DMA) is a recognized solvent known for its robust resistance to the highly reactive reduced oxygen species, yet its application in Li-O2 batteries has been constrained due to its poor compatibility with the Li metal anode. In this study, a rationally selected hydrofluoroether diluent, methyl nonafluorobutyl ether (M3), has been introduced into the DMA-based electrolyte to construct a localized high concentration electrolyte. The stable -CH3 and C-F bonds within the M3 structure could not only augment the fundamental properties of the electrolyte but also fortify its resilience against attacks from O2- and 1O2. Additionally, the strong electron-withdrawing groups (-F) presented in the M3 diluent could facilitate coordination with the electron-donating groups (-CH3) in the DMA solvent. This intermolecular interaction promotes more alignment of Li+-anions with a small amount of M3 addition, leading to the construction of an anion-derived inorganic-rich SEI that enhances the stability of the Li anode. As a result, the Li-O2 batteries with the DMA/M3 electrolyte exhibit superior cycling performance at both 30 °C (359th) and -10 °C (120th).

Ferroptosis-inducing compounds synergize with docetaxel to overcome chemoresistance in docetaxel-resistant non-small cell lung cancer cells.

Development of resistance to therapy-induced cell death is a major hurdle in the effective treatment of advanced solid tumors. Erastin and RSL3 were originally found to induce synthetic lethality by induction of a novel form of cell death termed ferroptosis. Emerging evidence suggests that ferroptosis inducers enhance chemosensitivity of classic therapeutic agents by triggering ferroptotic cell death. In this study we evaluated the effects of erastin and RSL3 on the resistance of docetaxel, doxorubicin, and cisplatin, and revealed a mechanism whereby these ferroptosis inducers augment docetaxel efficacy in non-small cell lung cancer by regulating redox signaling to promote ferroptosis. Transcriptome analysis revealed that combination treatment modulated not only p53 signaling pathway but also immune responses and several signaling pathways including MAPK, NF-κB and PI3K/Akt. Considering that glutathione peroxidase 4 (GPX4) serves as the main effector to protect cells from ferroptosis, this study identified three novel non-covalent GPX4 inhibitors with the aid of pharmacophore-based virtual screening. The new ferroptosis-inducing compounds synergized with docetaxel to increase the cytotoxicity by promoting ferroptotic cell death in docetaxel-resistant A549/DTX cells. Collectively, the induction of ferroptosis contributed to docetaxel-induced cytotoxic effects and overcame drug resistance in A549/DTX cells. Ferroptosis has a great potential to become a new approach to attenuate resistance to some classic therapeutic drugs in cancer patients.

Serum miR-192-5p is a promising biomarker for lethal radiation injury.

In the event of a nuclear or radiation accident, rapid identification is required for those who exposed to potentially lethal dose irradiation. However, existing techniques are not adequate for the classification of lethal injury. Several studies have explored the potential of miRNAs as biomarkers for ionizing radiation injury, however, there are few miRNAs with specific expression for lethal radiation injury. Therefore, the aim of this study was to screen and validate the possibility of serum miRNAs as biomarkers of lethal radiation injury. We found the specific expression of mmu-miR-374c-5p / mmu-miR-194-5p on first day and mmu-miR-192-5p / mmu-miR-223-3p on third day in the mouse serum only under 10Gy irradiation by miRNA sequencing and all significantly correlated with lymphocyte counts by Pearson's correlation analysis. In addition, it was found that among the 4 candidate serum miRNAs, only highly-expressed mmu-miR-192-5p in mouse serum irradiated at lethal doses was returned to sham-like expression levels at 3 days post-irradiation with amifostine pretreatment and closely correlated with survival rate. We demonstrated for the first time that mmu-miR-192-5p screened from lethally irradiated mice sera can be used as a potential biomarker for lethal irradiation injury, which will be helpful to improve efficiency of medical treatment to minimize casualties after a large-scale nuclear accident.

Two AIE-active Schiff base fluorescent probes for highly selective recognition of Cu2+ ions.

Two helical Schiff base compounds (H4TPA and H4TPE) containing a triphenylamine (TPA) or tetraphenylethylene (TPE) scaffold were successfully synthesized and characterized. Both H4TPA and H4TPE exhibited typical aggregation-induced emission characteristics in the mixed solvent of THF/H2O. The two compounds also showed high selectivity and sensitivity for the recognition of Cu2+ over other ions in THF/HEPES (1:4, V/V, pH = 7.4, 2.0 × 10-5 M), and could be used as turn-off fluorescent probes for Cu2+. The stoichiometric ratios and association constants were estimated via Job's plots and UV-vis spectra titration, and the detection limits of H4TPA and H4TPE toward Cu2+ were calculated to be 2.41 × 10-7 M and 1.38 × 10-7 M, respectively. Besides, the crystal structure of the complex obtained from the interaction of H4TPA with Cu2+ well illustrated the binding modes, which helped us understand the Cu2+ recognition mechanism of H4TPA and H4TPE. Moreover, the detection of Cu2+ and spiked recovery experiments were carried out, which indicated that the two probes can be applied to Cu2+ detection in real samples with satisfactory recoveries.

Fabrication of 3D CuFe2O4/Cu0 hierarchical nanostructures on carbon fiber paper by simple hydrothermal method for efficient detection of malachite green, sunset yellow and tartrazine in food samples.

In this study, a hydrothermal process was utilized to grow mixed-valence CuFe2O4/Cu0 nanosheets on carbon fiber paper, forming a three-dimensional hierarchical electrode (CuFe2O4/Cu0@CFP). The ordered array structure, coupled with the porous bowl-like structure, enhances the exposure of more electrode active sites and facilitates analyte penetration, thus enhancing the electrode sensing performance. As a binder-free sensor, the CuFe2O4/Cu0@CFP sensor exhibited remarkable sensitivity in detecting Malachite Green (MG), Sunset Yellow (SY) and Tartrazine (TA) over wide concentration ranges: 0.1-300 µM for MG (R2 = 0.994), 0.005-200 µM for SY (R2 = 0.996), and 0.005-300 µM for TA (R2 = 0.995) with low detection limits of 0.033 µM for MG, 0.0016 µM for SY, and 0.0016 µM for TA (S/N = 3), respectively. Additionally, the 3D CuFe2O4/Cu0@CFP sensor detected MG, SY, and TA in a mixed solution with satisfactory results. It also performs well in beverage, fruit juice powder, and jelly samples, with results matching those from HPLC.

SNORA28 Promotes Proliferation and Radioresistance in Colorectal Cancer Cells through the STAT3 Pathway by Increasing H3K9 Acetylation in the LIFR Promoter.

Radiotherapy is essential for treating colorectal cancer (CRC), especially in advanced rectal cancer. However, the low radiosensitivity of CRC cells greatly limits radiotherapy efficacy. Small nucleolar RNAs (snoRNAs) are a class of noncoding RNA that primarily direct post-transcriptional modifications of ribosomal RNAs (rRNAs), small nuclear RNAs (snRNAs), and other cellular RNAs. While snoRNAs are involved in tumor progression and chemoresistance, their association with radiosensitivity remains largely unknown. Herein, SNORA28 is shown highly expressed in CRC and is positively associated with poor prognosis. Furthermore, SNORA28 overexpression enhances the growth and radioresistance of CRC cells in vitro and in vivo. Mechanistically, SNORA28 acts as a molecular decoy that recruits bromodomain-containing protein 4 (BRD4), which increases the level of H3K9 acetylation at the LIFR promoter region. This stimulates LIFR transcription, which in turn triggers the JAK1/STAT3 pathway, enhancing the proliferation and radioresistance of CRC cells. Overall, these results highlight the ability of snoRNAs to regulate radiosensitivity in tumor cells and affect histone acetylation modification in the promoter region of target genes, thus broadening the current knowledge of snoRNA biological functions and the mechanism underlying target gene regulation.

A high-permeability method for extracting purple yam saponins based on ultrasonic-assisted natural deep eutectic solvent.

The extraction of active ingredients from traditional Chinese medicine has received considerable attentions. In this study, 16 kinds of natural deep eutectic solvent (NADES) with ultrasonic were selected to extract saponins from purple yam root and the extraction mechanism was investigated. The results showed that chloride/acrylic acid (1:2; n/n) had the highest extraction yield for saponins. The optimal extraction process parameters were 24% water content, 20 mL/g liquid-solid ratio, and ultrasonic extraction for 85 min (81 °C, 600 W). The extraction rate (ER) of purple yam saponins was 0.935%, close to the fitted result of 96.5 mg/g. Molecular dynamics simulations and FT-IR results showed that the NADES may extract the saponin constituents from purple yam through hydrogen bonding. Compared with traditional extraction methods and molecularly imprinted polymer methods, NADES has a higher ER and lower cost (1.53 $/g), which provides a reference for subsequent industrial quantitative production.

Precision Medicine to Redefine Insulin Secretion and Monogenic Diabetes-Randomized Controlled Trial (PRISM-RCT) in Chinese patients with young-onset diabetes: design, methods and baseline characteristics.

INTRODUCTION: We designed and implemented a patient-centered, data-driven, holistic care model with evaluation of its impacts on clinical outcomes in patients with young-onset type 2 diabetes (T2D) for which there is a lack of evidence-based practice guidelines. RESEARCH DESIGN AND METHODS: In this 3-year Precision Medicine to Redefine Insulin Secretion and Monogenic Diabetes-Randomized Controlled Trial, we evaluate the effects of a multicomponent care model integrating use of information and communication technology (Joint Asia Diabetes Evaluation (JADE) platform), biogenetic markers and patient-reported outcome measures in patients with T2D diagnosed at ≤40 years of age and aged ≤50 years. The JADE-PRISM group received 1 year of specialist-led team-based management using treatment algorithms guided by biogenetic markers (genome-wide single-nucleotide polymorphism arrays, exome-sequencing of 34 monogenic diabetes genes, C-peptide, autoantibodies) to achieve multiple treatment goals (glycated hemoglobin (HbA1c) <6.2%, blood pressure <120/75 mm Hg, low-density lipoprotein-cholesterol <1.2 mmol/L, waist circumference <80 cm (women) or <85 cm (men)) in a diabetes center setting versus usual care (JADE-only). The primary outcome is incidence of all diabetes-related complications. RESULTS: In 2020-2021, 884 patients (56.6% men, median (IQR) diabetes duration: 7 (3-12) years, current/ex-smokers: 32.5%, body mass index: 28.40±5.77 kg/m2, HbA1c: 7.52%±1.66%, insulin-treated: 27.7%) were assigned to JADE-only (n=443) or JADE-PRISM group (n=441). The profiles of the whole group included positive family history (74.7%), general obesity (51.4%), central obesity (79.2%), hypertension (66.7%), dyslipidemia (76.4%), albuminuria (35.4%), estimated glomerular filtration rate <60 mL/min/1.73 m2 (4.0%), retinopathy (13.8%), atherosclerotic cardiovascular disease (5.2%), cancer (3.1%), emotional distress (26%-38%) and suboptimal adherence (54%) with 5-item EuroQol for Quality of Life index of 0.88 (0.87-0.96). Overall, 13.7% attained ≥3 metabolic targets defined in secondary outcomes. In the JADE-PRISM group, 4.5% had pathogenic/likely pathogenic variants of monogenic diabetes genes; 5% had autoantibodies and 8.4% had fasting C-peptide <0.2 nmol/L. Other significant events included low/large birth weight (33.4%), childhood obesity (50.7%), mental illness (10.3%) and previous suicide attempts (3.6%). Among the women, 17.3% had polycystic ovary syndrome, 44.8% required insulin treatment during pregnancy and 17.3% experienced adverse pregnancy outcomes. CONCLUSIONS: Young-onset diabetes is characterized by complex etiologies with comorbidities including mental illness and lifecourse events. TRIAL REGISTRATION NUMBER: NCT04049149.

A new multifunctional phenanthroline-derived probe for colorimetric sensing of Fe2+ and fluorometric sensing of Zn2.

A new phenanthroline derivative bearing imidazole group, (2-(3,5-di(pyridin-4-yl)phenyl)-1-p-tolyl-1H-imidazo[4,5-f][1,10]phenanthroline) (1), has been devised. 1 can be used as a multifunctional probe exhibiting a highly sensitive colorimetric response to Fe2+ and a selectively ratiometric fluorescent response to Zn2+ in a buffer-ethanol solution. The absorption enhancement accompanied by a visual color change from colorless to red upon addition of Fe2+, makes 1 a suitable naked-eye sensor for Fe2+. Moreover, 1 displayed a Zn2+-induced red-shift of emission (44 nm) showing a color change from blue to light cyan under a 365-nm UV lamp. Its practical imaging applicability for intracellular Zn2+ was confirmed in HeLa cells using a confocal microscope. The improved emission properties and cell imaging capability would provide a new approach for fluorescence sensation for Zn2+.

Enhanced sinks of polystyrene nanoplastics (PSNPs) in marine sediment compared to freshwater sediment: Influencing factors and mechanisms.

The difference in the transport behaviors of nanoplastics consistently assistant with their toxicities to benthic and other aquatic organisms is still unclear between freshwater and marine sediments. Here, the mobilities of polystyrene nanoplastics (PSNPs) and key environmental factors including salinity and humic acid (HA) were systematically studied. In the sand column experiments, both tested PSNPs in the freshwater system (100 nm NPs (100NPs): 90.15 %; 500 nm NPs (500NPs): 54.22 %) presented much higher penetration ratio than in the marine system (100NPs: 8.09 %; 500NPs: 19.04 %). The addition of marine sediment with a smaller median grain diameter caused a much more apparent decline in NPs mobility (100NPs: from 8.09 % to 1.85 %; 500NPs: from 19.04 % to 3.51 %) than that containing freshwater sediment (100NPs: from 90.15 % to 83.56 %; 500NPs: from 54.22 % to 41.63 %). Interestingly, adding HA obviously led to decreased and slightly increased mobilities for NPs in freshwater systems, but dramatically improved performance for NPs in marine systems. Electrostatic and steric repulsions, corresponding to alteration of zeta potential and hydrodynamic diameter of NPs and sands, as well as minerals owing to adsorption of dissolved organic matter (DOM) and aggregations from varied salinity, are responsible for the mobility difference.

Analysis of Factors Influencing the Stigma Associated with Postoperative Cervical Cancer Patients and the Impact of Integrated Nursing Interventions on Stigma.

Objective: To investigate the influencing factors related to stigma and nursing interventions for patients after cervical cancer surgery. Methods: The clinical data of 158 patients with cervical cancer treated with radical cervical cancer in Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology from November 2016 to December 2021 were retrospectively analyzed. The patients were divided into a research group (79 cases) and a control group (79 cases) based on the random number method. In the control group, patients were given general nursing instructions during the post-operative visit. In contrast, the research group provided comprehensive nursing interventions to patients and their families based on the observation group. The Social Impact Scale (SIS) was used to assess the patients' stigma; the Self-Rating Anxiety Scale (SAS), Trait Coping Style Questionnaire (TCSQ), and Quality of Life Questionnaire for Cancer Patients (QLQ-C30) were also used to assess the patients' pre- and post-care interventions. The patients' status was assessed before and after the intervention. Results: The SIS score (49.68±8.41) and TCSQ negative coping score (30.14±7.06) of the patients in the research group after the nursing intervention were much smaller than those in the control group, and the TCSQ positive coping score (40.36±6.51) was much larger than that of the control group (P < .05). The SAS anxiety score (31.65±7.36) was much smaller, and the QLQ-C30 score (78.65±16.59) was much larger in the research group than in the control group after the nursing intervention (P < .05). Conclusion: Risk factors affecting postoperative cervical cancer patients' sense of stigma include age 18-35 years, high school and above, employed, monthly income >3000 RMB, family history of the disease, disease duration >5 years, and postoperative chemotherapy, etc. Comprehensive clinical interventions can be given to patients with these conditions to reduce the sense of stigma.

Cedrol alleviates postmenopausal osteoporosis in rats through inhibiting the activation of the NF-κB signaling pathway.

Pharmacological studies have shown that Cedrol (CE) exhibits extensive biological activities, including anti-inflammatory and analgesic. Moreover, it can inhibit the NF-κB pathway and the expression of various associated proteins. This study aimed to investigate the role of CE in postmenopausal osteoporosis. The results showed that intragastric administration of CE (10 and 20 mg/kg) significantly improved the bone microstructure damage and increased bone mineral density, trabecular bone volume, and bone trabecular thickness in ovariectomized (OVX) rats (p < 0.05). CE treatment additionally made a well-organized arrangement of bone trabeculae and improved its thickness and density. Compared with the OVX group, the levels of tartrate-resistant acid phosphatase from 5b and C-terminal telopeptide of type I collagen were significantly reduced by 42.75% and 49.27% in the OVX + CE rats (p < 0.05). TRAP staining visually showed that the number of osteoclasts in the femur tissue of CE-treated rats was less than that of the OVX group. The expressions of nuclear factor of activated T-cells, cytoplasmic 1, acid phosphatase 5, and cathepsin K in OVX + CE rats were significantly decreased by 51.61%, 46.07%, and 50.34% compared to the OVX group (p < 0.01). In addition, CE intervention effectively reduced the phosphorylation levels of P65 and IκBα and inhibited the NF-κB signaling pathway. Meanwhile, CE diminished the number of multinucleated osteoclasts induced by receptor activator for nuclear factor-κB ligand and hindered cell fusion as well as nuclear translocation of osteoclast precursor cells P65. In conclusion, CE inhibits osteoclastogenesis by suppressing the activation of the NF-κB signaling pathway, thereby alleviating postmenopausal osteoporosis.

Prevotella copri promotes vascular calcification via lipopolysaccharide through activation of NF-κB signaling pathway.

Emerging evidence indicates that alteration of gut microbiota plays an important role in chronic kidney disease (CKD)-related vascular calcification (VC). We aimed to investigate the specific gut microbiota and the underlying mechanism involved in CKD-VC. We identified an increased abundance of Prevotella copri (P. copri) in the feces of CKD rats (induced by using 5/6 nephrectomy followed by a high calcium and phosphate diet) with aortic calcification via amplicon sequencing of 16S rRNA genes. In patients with CKD, we further confirmed a positive correlation between abundance of P. copri and aortic calcification scores. Moreover, oral administration of live P. copri aggravated CKD-related VC and osteogenic differentiation of vascular smooth muscle cells in vivo, accompanied by intestinal destruction, enhanced expression of Toll-like receptor-4 (TLR4), and elevated lipopolysaccharide (LPS) levels. In vitro and ex vivo experiments consistently demonstrated that P. copri-derived LPS (Pc-LPS) accelerated high phosphate-induced VC and VSMC osteogenic differentiation. Mechanistically, Pc-LPS bound to TLR4, then activated the nuclear factor κB (NF-κB) and nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome signals during VC. Inhibition of NF-κB reduced NLRP3 inflammasome and attenuated Pc-LPS-induced VSMC calcification. Our study clarifies a novel role of P. copri in CKD-related VC, by the mechanisms involving increased inflammation-regulating metabolites including Pc-LPS, and activation of the NF-κB/NLRP3 signaling pathway. These findings highlight P. copri and its-derived LPS as potential therapeutic targets for VC in CKD.

Adjuvant treatment strategy evolution and risk stratification for hormone receptor-positive, human epidermal growth factor receptor-2 negative early breast cancer in China.

BACKGROUND: Patients with hormone receptor-positive (HR+), human epidermal growth factor receptor-2 negative (HER2-) early breast cancer (EBC) with high-risk clinicopathological features face an increased risk of recurrence. This study explored the evolving treatment landscape and clinical outcomes in patients with EBC using a nationwide database. PATIENTS AND METHODS: The study cohort comprised HR+/HER2-, stages 1-3, patients with EBC who underwent surgery and received adjuvant endocrine therapy (AET) from January 2013 to March 2021. High-risk patients were defined by ≥4 positive axillary lymph nodes, or 1-3 positive lymph node(s) with at least one high-risk feature (histologic grade 3, tumor size ≥5 cm, or Ki-67 ≥20%). A low-risk cohort included patients not meeting the criteria. Survival analysis was conducted with a cutoff of September 2021. RESULTS: The study included 4088 eligible patients (1310 high-risk patients and 2778 low-risk patients). High-risk patients were more likely to receive adjuvant chemotherapy and radiotherapy compared to low-risk patients. From 2013 to 2021, an increasing proportion of patients received aromatase inhibitors and ovarian function suppression as part of their AET. The 2-, 5-, and 7-year invasive disease-free survival for high-risk cohort were 90.67%, 75.26%, and 57.10%, respectively, these rates were notably higher for low-risk cohort at 97.14%, 89.85%, and 84.83%. High-risk patients demonstrated a higher risk of recurrence or death compared with low-risk patients (hazard ratio, 2.38; 95% CI, 1.82-3.12). CONCLUSION: In the setting of standard or even intensive AET, patients with EBC with high-risk features still present high recurrence risk, highlighting the urgent need for innovative adjuvant treatment strategies.

Serum sSelectin-L is an early specific indicator of radiation injury.

Objective: It's crucial to identify an easily detectable biomarker that is specific to radiation injury in order to effectively classify injured individuals in the early stage in large-scale nuclear accidents. Methods: C57BL/6J mice were subjected to whole-body and partial-body γ irradiation, as well as whole-body X-ray irradiation to explore the response of serum sSelectin-L to radiation injury. Then, it was compared with its response to lipopolysaccharide-induced acute infection and doxorubicin-induced DNA damage to study the specificity of sSelectin-L response to radiation. Furthermore, it was further evaluated in serum samples from nasopharyngeal carcinoma patients before and after radiotherapy. Simulated rescue experiments using Amifostine or bone marrow transplantation were conducted in mice with acute radiation syndrome to determine the potential for establishing sSelectin-L as a prognostic marker. The levels of sSelectin-L were dynamically measured using the ELISA method. Results: Selectin-L is mainly expressed in hematopoietic tissues and lymphatic tissues. Mouse sSelectin-L showed a dose-dependent decrease from 1 day after irradiation and exhibited a positive correlation with lymphocyte counts. Furthermore, the level of sSelectin-L reflected the degree of radiation injury in partial-body irradiation mice and in nasopharyngeal carcinoma patients. sSelectin-L was closely related to the total dose of γ or X ray. There was no significant change in the sSelectin-L levels in mice intraperitoneal injected with lipopolysaccharide or doxorubicin. The sSelectin-L was decreased slower and recovered faster than lymphocyte count in acute radiation syndrome mice treated with Amifostine or bone marrow transplantation. Conclusions: Our study shows that sSelectin-L has the potential to be an early biomarker to classify injured individuals after radiation accidents, and to be a prognostic indicator of successful rescue of radiation victims.

A nomogram-based prediction model for dysphagia in patients with chronic obstructive pulmonary disease: A cross-sectional study.

AIM AND OBJECTIVES: To investigate the prevalence of dysphagia in patients with COPD, identify the risk factors for dysphagia, develop a visual clinical prediction model and quantitatively predict the probability of developing dysphagia. BACKGROUND: Patients with COPD are at high risk of dysphagia, which is strongly linked to the acute exacerbation of their condition. The use of effective tools to predict its risk may contribute to the early identification and treatment of dysphagia in patients with COPD. DESIGN: A cross-sectional design. METHODS: From July 2021 to April 2023, we enrolled 405 patients with COPD for this study. The clinical prediction model was constructed according to the results of a univariate analysis and a logistic regression analysis, evaluated by discrimination, calibration and decision curve analysis and visualized by a nomogram. This study was reported using the TRIPOD checklist. RESULTS: In total, 405 patients with COPD experienced dysphagia with a prevalence of 59.01%. A visual prediction model was constructed based on age, whether combined with cerebrovascular disease, chronic pulmonary heart disease, acute exacerbation of COPD, home noninvasive positive pressure ventilation, dyspnoea level and xerostomia level. The model exhibited excellent discrimination at an AUC of .879. Calibration curve analysis indicated a good agreement between experimental and predicted values, and the decision curve analysis showed a high clinical utility. CONCLUSION: The model we devised may be used in clinical settings to predict the occurrence of dysphagia in patients with COPD at an early stage. RELEVANCE TO CLINICAL PRACTICE: The model can help nursing staff to calculate the risk probability of dysphagia in patients with COPD, formulate personalized preventive care measures for high-risk groups as soon as possible to achieve early prevention or delay of dysphagia and its related complications and improve the prognosis. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

Parametric analysis of craniocerebral injury mechanism in pedestrian traffic accidents based on finite element methods.

PURPOSE: The toughest challenge in pedestrian traffic accident identification lies in ascertaining injury manners. This study aimed to systematically simulate and parameterize 3 types of craniocerebral injury including impact injury, fall injury, and run-over injury, to compare the injury response outcomes of different injury manners. METHODS: Based on the total human model for safety (THUMS) and its enhanced human model THUMS-hollow structures, a total of 84 simulations with 3 injury manners, different loading directions, and loading velocities were conducted. Von Mises stress, intracranial pressure, maximum principal strain, cumulative strain damage measure, shear stress, and cranial strain were employed to analyze the injury response of all areas of the brain. To examine the association between injury conditions and injury consequences, correlation analysis, principal component analysis, linear regression, and stepwise linear regression were utilized. RESULTS: There is a significant correlation observed between each criterion of skull and brain injury (p < 0.01 in all Pearson correlation analysis results). A 2-phase increase of cranio-cerebral stress and strain as impact speed increases. In high-speed impact (> 40 km/h), the Von Mises stress on the skull was with a high possibility exceed the threshold for skull fracture (100 MPa). When falling and making temporal and occipital contact with the ground, the opposite side of the impacted area experiences higher frequency stress concentration than contact at other conditions. Run-over injuries tend to have a more comprehensive craniocerebral injury, with greater overall deformation due to more adequate kinetic energy conduction. The mean value of maximum principal strain of brain and Von Mises stress of cranium at run-over condition are 1.39 and 403.8 MPa, while they were 1.31, 94.11 MPa and 0.64, 120.5 MPa for the impact and fall conditions, respectively. The impact velocity also plays a significant role in craniocerebral injury in impact and fall loading conditions (the p of all F-test < 0.05). A regression equation of the craniocerebral injury manners in pedestrian accidents was established. CONCLUSION: The study distinguished the craniocerebral injuries caused in different manners, elucidated the biomechanical mechanisms of craniocerebral injury, and provided a biomechanical foundation for the identification of craniocerebral injury in legal contexts.

Machine learning algorithms to predict colistin-induced nephrotoxicity from electronic health records in patients with multidrug-resistant Gram-negative infection.

OBJECTIVES: Colistin-induced nephrotoxicity prolongs hospitalisation and increases mortality. The study aimed to construct machine learning models to predict colistin-induced nephrotoxicity in patients with multidrug-resistant Gram-negative infection. METHODS: Patients receiving colistin from three hospitals in the Clinical Research Database were included. Data were divided into a derivation cohort (2011-2017) and a temporal validation cohort (2018-2020). Fifteen machine learning models were established by categorical boosting, light gradient boosting machine and random forest. Classifier performances were compared by the sensitivity, F1 score, Matthews correlation coefficient (MCC), area under the receiver operating characteristic (AUROC) curve, and area under the precision-recall curve (AUPRC). SHapley Additive exPlanations plots were drawn to understand feature importance and interactions. RESULTS: The study included 1392 patients, with 360 (36.4%) and 165 (40.9%) experiencing nephrotoxicity in the derivation and temporal validation cohorts, respectively. The categorical boosting with oversampling achieved the highest performance with a sensitivity of 0.860, an F1 score of 0.740, an MCC of 0.533, an AUROC curve of 0.823, and an AUPRC of 0.737. The feature importance demonstrated that the days of colistin use, cumulative dose, daily dose, latest C-reactive protein, and baseline haemoglobin were the most important risk factors, especially for vulnerable patients. A cutoff colistin dose of 4.0 mg/kg body weight/d was identified for patients at higher risk of nephrotoxicity. CONCLUSIONS: Machine learning techniques can be an early identification tool to predict colistin-induced nephrotoxicity. The observed interactions suggest a modification in dose adjustment guidelines. Future geographic and prospective validation studies are warranted to strengthen the real-world applicability.

Seasonal patterns, fate and ecological risk assessment of pharmaceutical compounds in a wastewater treatment plant with Bacillus bio-reactor treatment.

Pharmaceutical compounds (PhCs) pose a growing concern with potential environmental impacts, commonly introduced into the environment via wastewater treatment plants (WWTPs). The occurrence, removal, and season variations of 60 different classes of PhCs were investigated in the baffled bioreactor (BBR) wastewater treatment process during summer and winter. The concentrations of 60 PhCs were 3400 ± 1600 ng/L in the influent, 2700 ± 930 ng/L in the effluent, and 2400 ± 120 ng/g dw in sludge. Valsartan (Val, 1800 ng/L) was the main contaminant found in the influent, declining to 520 ng/L in the effluent. The grit chamber and BBR tank were substantially conducive to the removal of VAL. Nonetheless, the BBR process showcased variable removal efficiencies across different PhC classes. Sulfadimidine had the highest removal efficiency of 87 ± 17% in the final effluent (water plus solid phase). Contrasting seasonal patterns were observed among PhC classes within BBR process units. The concentrations of many PhCs were higher in summer than in winter, while some macrolide antibiotics exhibited opposing seasonal fluctuations. A thorough mass balance analysis revealed quinolone and sulfonamide antibiotics were primarily eliminated through degradation and transformation in the BBR process. Conversely, 40.2 g/d of macrolide antibiotics was released to the natural aquatic environment via effluent discharge. Gastric acid and anticoagulants, as well as cardiovascular PhCs, primarily experienced removal through sludge adsorption. This study provides valuable insights into the intricate dynamics of PhCs in wastewater treatment, emphasizing the need for tailored strategies to effectively mitigate their release and potential environmental risks.