Causal relationship between immune cells and pulmonary arterial hypertension: Mendelian randomization analysis.

Immunity and inflammation in pulmonary arterial hypertension (PAH) has gained more attention. This research aimed to investigate the potential causal connections between 731 immunophenotypes and the likelihood of developing PAH. We obtained immunocyte data and PAH from openly accessible database and used Mendelian randomization (MR) analysis to evaluate the causal association between each immunophenotype and PAH. Various statistical methods were employed: the MR-Egger, weighted median, inverse variance weighted (IVW), simple mode, and weighted mode. In the study of 731 different types of immune cells, it was found that 9 showed a potential positive connection (IVW P < .05) with increased risk of PAH, while 19 had a possible negative link to decreased risk. Following false discovery rate (FDR) adjustment, the analysis using the IVW method demonstrated that 5 immune phenotypes were significantly associated with PAH (FDR < 0.05, OR > 1). Conversely, there was a negative correlation between PAH and 4 immune cell types (FDR < 0.05, OR < 1). Sensitivity analyses suggested the robustness of all MR findings. This research, for the first time, has revealed indicative evidence of a causal link between circulating immune cell phenotypes and PAH through genetic mechanisms. These results underscore the importance of immune cells in the pathogenesis of PAH.

Microbial signatures predictive of short-term prognosis in severe pneumonia.

Objective: This retrospective cohort study aimed to investigate the composition and diversity of lung microbiota in patients with severe pneumonia and explore its association with short-term prognosis. Methods: A total of 301 patients diagnosed with severe pneumonia underwent bronchoalveolar lavage fluid metagenomic next-generation sequencing (mNGS) testing from February 2022 to January 2024. After applying exclusion criteria, 236 patients were included in the study. Baseline demographic and clinical characteristics were compared between survival and non-survival groups. Microbial composition and diversity were analyzed using alpha and beta diversity metrics. Additionally, LEfSe analysis and machine learning methods were employed to identify key pathogenic microorganism associated with short-term mortality. Microbial interaction modes were assessed through network co-occurrence analysis. Results: The overall 28-day mortality rate was 37.7% in severe pneumonia. Non-survival patients had a higher prevalence of hypertension and exhibited higher APACHE II and SOFA scores, higher procalcitonin (PCT), and shorter hospitalization duration. Microbial α and ß diversity analysis showed no significant differences between the two groups. However, distinct species diversity patterns were observed, with the non-survival group showing a higher abundance of Acinetobacter baumannii, Klebsiella pneumoniae, and Enterococcus faecium, while the survival group had a higher prevalence of Corynebacterium striatum and Enterobacter. LEfSe analysis identified 29 distinct terms, with 10 potential markers in the non-survival group, including Pseudomonas sp. and Enterococcus durans. Machine learning models selected 16 key pathogenic bacteria, such as Klebsiella pneumoniae, significantly contributing to predicting short-term mortality. Network co-occurrence analysis revealed greater complexity in the non-survival group compared to the survival group, with differences in central genera. Conclusion: Our study highlights the potential significance of lung microbiota composition in predicting short-term prognosis in severe pneumonia patients. Differences in microbial diversity and composition, along with distinct microbial interaction modes, may contribute to variations in short-term outcomes. Further research is warranted to elucidate the clinical implications and underlying mechanisms of these findings.

Special education teachers' emotional intelligence and its relationships with social support, work engagement and job performance: a job demands-resources theory's perspective.

Based on the Job Demands-Resources theory, this research investigated the multiple mediating role of special education teachers' social support and work engagement in the relationship between their emotional intelligence and job performance. Data of 710 Chinese mainland teachers in special education schools were analyzed. The results showed that emotional intelligence directly predicted job performance. Both social support and work engagement partially mediated the relationship between emotional intelligence and job performance. Furthermore, social support and work engagement serially mediated the relationship between emotional intelligence and job performance. The limitations and implications for future studies and practices are discussed.

Synergistic and stepwise treatment of resveratrol and catechol in Haematococcus pluvialis for the overproduction of biomass and astaxanthin.

To increase the production of biomass and astaxanthin from Haematococcus pluvialis to meet the high market demand for astaxanthin, this study recruited two typical and negligible phytohormones (namely resveratrol and catechol) for the stepwise treatments of H. pluvialis. It was found that the hybrid and sequential treatments of resveratrol (200 µmol) and catechol (100 µmol) had achieved the maximum astaxanthin content at 33.96 mg/L and 42.99 mg/L, respectively. Compared with the hybrid treatment, the physiological data of H. pluvialis using the sequential strategy revealed that the enhanced photosynthetic performance via the Calvin cycle by RuBisCO improved the biomass accumulation during the macrozooid stage; meanwhile, the excessive ROS production had occurred to enhance astaxanthin production with the help of NADPH overproduction during the hematocyst stage. Overall, this study provides improved knowledge of the impacts of phytohormones in improving biomass and astaxanthin of H. pluvialis, which shed valuable insights for advancing microalgae-based biorefinery.

Ozone Chemistry on Greasy Glass Surfaces Affects the Levels of Volatile Organic Compounds in Indoor Environments.

The chemistry of ozone (O3) on indoor surfaces leads to secondary pollution, aggravating the air quality in indoor environments. Here, we assess the heterogeneous chemistry of gaseous O3 with glass plates after being 1 month in two different kitchens where Chinese and Western styles of cooking were applied, respectively. The uptake coefficients of O3 on the authentic glass plates were measured in the dark and under UV light irradiation typical for indoor environments (320 nm < λ < 400 nm) at different relative humidities. The gas-phase product compounds formed upon reactions of O3 with the glass plates were evaluated in real time by a proton-transfer-reaction quadrupole-interface time-of-flight mass spectrometer. We observed typical aldehydes formed by the O3 reactions with the unsaturated fatty acid constituents of cooking oils. The formation of decanal, 6-methyl-5-hepten-2-one (6-MHO), and 4-oxopentanal (4-OPA) was also observed. The employed dynamic mass balance model shows that the estimated mixing ratios of hexanal, octanal, nonanal, decanal, undecanal, 6-MHO, and 4-OPA due to O3 chemistry with authentic grime-coated kitchen glass surfaces are higher in the kitchen where Chinese food was cooked compared to that where Western food was cooked. These results show that O3 chemistry on greasy glass surfaces leads to enhanced VOC levels in indoor environments.

Identifying the origin of Laggera crispata (Vahl) Hepper & J. R. I. Wood based on UPLC fingerprinting and chemometrics.

In this study, thirty-four samples of Laggera crispata (Vahl) Hepper & J. R. I. Wood from five main production areas in Yunnan Province, were collected for experimentation. UPLC- PDA was used to generate fingerprints and the common peaks were analysed through R and SIMCA-P. L. crispata from different origins can be distinguished by OPLS-DA and PCA. The VIP values were compared, and 8 characteristic components with great differences were obtained. It was confirmed that the two characteristic components were chrysosplenetin and artemisetin, and the quantitative analysis was performed with these two compounds from L. crispata samples with different origins. Based on the variance analysis results, the most significant difference in the content of chrysosplendin and artemisin was in Lancang and Honghe and Lancang and Simao, respectively. The chrysosplenetin can be used as an important indicator for quality control and to trace the origin of L. crispata.

Development and external validation of a nomogram for predicting short-term prognosis in patients with acute pulmonary embolism.

BACKGROUND: Accurate assessment and timely intervention play a crucial role in ameliorating poor short-term prognosis of acute pulmonary embolism (APE) patients. The currently employed scoring models exhibit a degree of complexity, and some models may not comprehensively incorporate relevant indicators, thereby imposing limitations on the evaluative efficacy. Our study aimed to construct and externally validate a nomogram that predicts 30-day all-cause mortality risk in APE patients. METHODS: Clinical data from APE patients in Intensive Care-IV database was included as a training cohort. Additionally, we utilized our hospital's APE database as an external validation cohort. The nomogram was developed, and its predictive ability was evaluated using receiver operating characteristic (ROC) curves, calibration plots and decision curve analysis. RESULTS: A collective of 1332 patients and 336 patients were respectively enrolled as the training cohort and the validation cohort in this study. Five variables including age, malignancy, oxygen saturation, blood glucose, and the use of vasopressor, were identified based on the results of the multivariate Cox regression model. The ROC value for the nomogram in the training cohort yielded 0.765, whereas in the validation group, it reached 0.907. Notably, these values surpassed the corresponding ROC values for the Pulmonary Embolism Severity Index, which were 0.713 in the training cohort and 0.754 in the validation cohort. CONCLUSIONS: The nomogram including five indicators had a good performance in predicting short-term prognosis in patients with APE, which was easier to apply and provided better recommendations for clinical decision-making.

Continuous selenite biotransformation and biofuel production by marine diatom in the presence of fulvic acid.

In this study, the biochemical response of Phaeodactylum tricornutum to varying concentrations of inorganic selenium (Se) was investigated. It was observed that, when combined with fulvic acid, P. tricornutum exhibited enhanced uptake and biotransformation of inorganic Se, as well as increased microalgal lipid biosynthesis. Notably, when subjected to moderate (5 and 10 mg/L) and high (20 and 40 mg/L) concentrations of selenite under fulvic acid treatment, there was a discernible redirection of carbon flux towards lipogenesis and protein biosynthesis from carbohydrates. In addition, the key parameters of microalgae-based biofuels aligned with the necessary criteria outlined in biofuel regulations. Furthermore, the Se removal capabilities of P. tricornutum, assisted by fulvic acid, were coupled with the accumulation of substantial amounts of organic Se, specifically SeCys. These findings present a viable and successful approach to establish a microalgae-based system for Se uptake and biotransformation.

Neoadjuvant pertuzumab plus trastuzumab in combination with chemotherapy for human epidermal growth factor receptor 2 positive breast cancer: a real-world retrospective single-institutional study in China.

INTRODUCTION: Real-world studies on neoadjuvant dual anti-HER2 therapy combined with chemotherapy for breast cancer (BC) are scarce in China. This study aimed to evaluate the efficacy and safety of neoadjuvant dual anti-HER2 therapy combined with chemotherapy in a real-world setting. Moreover, differences in estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and proliferation cell nuclear antigen (Ki-67) expression pre- and post-neoadjuvant therapy were analyzed. METHODS: Clinical and pathological data of patients with HER2-positive BC who received neoadjuvant dual anti-HER2 therapy combined with chemotherapy at Liaoning Cancer Hospital & Institute, China, between September 2021 and September 2023, were retrospectively reviewed. RESULTS: Among 179 included patients, a pathologic complete response (pCR) was achieved in 109 patients (60.9%). The univariate analysis results indicated that the hormone receptor (HR) status (P = 0.013), HER2 status (P = 0.003), and cycles of targeted treatment (P = 0.035) were significantly correlated with pCR. Subsequent multivariable analysis showed that HR negative and HER2 status 3 + were independent predictive factors of pCR. Anemia was the most common adverse event (62.0%), and the most common grade 3-4 adverse event was neutropenia (6.1%). The differences in HER2 (34.5%) and Ki-67 (92.7%) expression between core needle biopsy and the residual tumor after neoadjuvant therapy were statistically significant, whereas the differences were insignificant in terms of ER or PR status. CONCLUSIONS: The combination of neoadjuvant trastuzumab and pertuzumab with chemotherapy showed good efficiency, and the toxic side effects were tolerable in patients with BC. In cases where pCR was not achieved after neoadjuvant therapy, downregulation of HER2 and Ki-67 expressions was observed.

A conjugate vaccine strategy that induces protective immunity against arecoline.

Betel-quid chewing addiction is the leading cause of oral submucous fibrosis and oral cancer, resulting in significant socio-economic burdens. Vaccination may serve as a promising potential remedy to mitigate the abuse and combat accidental overdose of betel nut. Hapten design is the crucial factor to the development of arecoline vaccine that determines the efficacy of a candidate vaccine. Herein, we reported that two kinds of novel arecoline-based haptens were synthesized and conjugated to Bovine Serum Albumin (BSA) to generate immunogens, which generated antibodies with high affinity for arecoline but reduced binding for guvacoline and no affinity for arecaidine or guvacine. Notably, vaccination with Arec-N-BSA, which via the N-position on the tetrahydropyridine ring (tertiary amine group), led to a higher antibody affinity compared to Arec-CONH-BSA, blunted analgesia and attenuated hypothermia for arecoline.

Botulinum toxin type A inhibits M1 macrophage polarization by deactivation of JAK2/STAT1 and IκB/NFκB pathway and contributes to scar alleviation in aseptic skin wound healing.

The non-neuronal and non-muscular effects of botulinum toxin type A (BTXA) on scar reduction has been discovered. This study was designed to investigate the effects of BTXA on macrophages polarization during the early stage of skin repair. A skin defect model was established on the dorsal skin of SD rats. BTXA was intracutaneous injected into the edge of wound immediately as the model was established. Histological examinations were performed on scar samples. Raw 264.7 was selected as the cell model of recruited circulating macrophages, and was induced for M1 polarization by LPS. Identify the signaling pathways that primarily regulated M1 polarization and respond to BTXA treatment. Application of BTXA at early stage of injury significantly reduced the scar diameter without delaying wound closure. BTXA treatment improved fiber proliferation and arrangement, and inhibited angiogenesis in scar granular tissue. The number of M1 macrophages and the levels of pro-inflammation were decreased after treated with BTXA in scar tissues. LPS activated JAK2/STAT1 and IκB/NFκB pathways were downregulated by BTXA, as well as LPS induced M1 polarization. At early stage of skin wound healing, injection of BTXA effectively reduced the number of M1 macrophages and the levels of pro-inflammatory mediators which contributes to scar alleviation. BTXA resisted the M1 polarization of macrophages induced by LPS via deactivating the JAK2/STAT1 and IκB/NFκB pathways.

Association of Combined Healthy Lifestyle Factors With Incident Dementia in Participants With and Without Multimorbidity: A Large Population-Based Prospective Cohort Study.

BACKGROUND: The effect of a healthy lifestyle on dementia associated with multimorbidity is not well understood. Our objective is to examine whether the adoption of a healthy lifestyle could potentially reduce the elevated risk of dementia in individuals with and without multimorbidity. METHODS: We utilized data from the UK Biobank cohort. A comprehensive healthy lifestyle score, ranging from 0 to 6, was generated. Cox proportional hazards models were used to examine the associations between multimorbidity, the healthy lifestyle score, and the incidence risk of dementia. RESULTS: Over a median follow-up period of 12.5 years, 5 852 all-cause dementia were recorded. Multimorbidity including cardiovascular, metabolic, neuropsychiatric, and inflammation-related diseases was associated with a higher risk of subsequent dementia. Each additional chronic disease was associated with a hazard ratio (HR) of 1.38 (95% CI: 1.33, 1.44). Compared to individuals without multimorbidity and a healthy lifestyle score of 5-6, patients with multimorbidity and a lifestyle score of 0-1 had a significantly higher risk of dementia (HR: 3.13; 95% CI: 2.64, 3.72), but the risk was markedly attenuated among those with multimorbidity and a lifestyle score of 5-6. Among patients with 3 or more diseases, the HR for dementia was 0.53 (95%CI: 0.42, 0.68) when comparing a lifestyle score of 5-6 to 0-1. And we observed more pronounced association between them among people younger than 60 years old. CONCLUSIONS: Adherence to a combination of healthy lifestyle factors, especially at a young age, was associated with a significantly lower risk of dementia among participants with multimorbidity.

Diterpenoid tanshinones inhibit gastric cancer angiogenesis through the PI3K/Akt/mTOR signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Salvia miltiorrhiza Bunge is a kind of Chinese herbal medicine known for activating blood circulation and removing blood stasis, with the effect of cooling blood and eliminating carbuncles, and has been proven to have the effect of treating tumors. However, the inhibitory effect of Salvia miltiorrhiza Bunge extracts (Diterpenoid tanshinones) on tumors by inhibiting angiogenesis has not been studied in detail. AIM OF THE STUDY: This study aimed to investigate the anti-gastric cancer effect of diterpenoid tanshinones (DT) on angiogenesis, including the therapeutic effects and pathways. MATERIALS AND METHODS: This experiment utilized network pharmacology was used to identify relevant targets and pathways of Salvia miltiorrhiza Bunge-related components in the treatment of gastric cancer. The effects of DT on the proliferation and migration of human gastric cancer cell line SGC-7901 and human umbilical vein endothelial cell line HUVECs were evaluated, and changes in the expression of angiogenesis-related factors were measured. In vivo, experiments were conducted on nude mice to determine tumor activity, size, immunohistochemistry, and related proteins. RESULTS: The findings showed that DT could inhibit the development of gastric cancer by suppressing the proliferation of gastric cancer cells, inducing apoptosis, and inhibiting invasion and metastasis. In addition, the content of angiogenesis-related factors and proteins was significantly altered in DT-affected cells and animals. CONCLUSIONS: Results suggest that DT has potential as a therapeutic agent for the treatment of gastric cancer, as it can inhibit tumor growth and angiogenesis. It was also found that DT may affect the expression of the angiogenic factor VEGF through the PI3K/Akt/mTOR pathway, leading to the regulation of tumor angiogenesis. This study provides a new approach to the development of anti-tumor agents and has significant theoretical and clinical implications for the treatment of gastric cancer.

EGR1 transcriptionally regulates SVEP1 to promote proliferation and migration in human coronary artery smooth muscle cells.

A low-frequency variant of sushi, von Willebrand factor type A, EGF, and pentraxin domain-containing protein 1 (SVEP1) is associated with the risk of coronary artery disease, as determined by a genome-wide association study. SVEP1 induces vascular smooth muscle cell proliferation and an inflammatory phenotype to promote atherosclerosis. In the present study, qRT‒PCR demonstrated that the mRNA expression of SVEP1 was significantly increased in atherosclerotic plaques compared to normal tissues. Bioinformatics revealed that EGR1 was a transcription factor for SVEP1. The results of the luciferase reporter assay, siRNA interference or overexpression assay, mutational analysis and ChIP confirmed that EGR1 positively regulated the transcriptional activity of SVEP1 by directly binding to its promoter. EGR1 promoted human coronary artery smooth muscle cell (HCASMC) proliferation and migration via SVEP1 in response to oxidized low-density lipoprotein (ox-LDL) treatment. Moreover, the expression level of EGR1 was increased in atherosclerotic plaques and showed a strong linear correlation with the expression of SVEP1. Our findings indicated that EGR1 binding to the promoter region drive SVEP1 transcription to promote HCASMC proliferation and migration.

Suppurative Meningitis Complicated with Arthritis Caused by Streptococcus Suis Infection: A Case Report.

Background: Streptococcus suis (S. suis) is a common gram-positive bacterium in pigs. Its natural infection sites are the upper respiratory tract (especially tonsils and nasal cavity), reproductive tract and digestive tract of pigs. It is a new emerging human and animal disease. A co-morbid pathogen that can cause serious infections in humans, including meningitis, sepsis, septic arthritis, and sometimes deafness. No cases have been reported in Huzhou City, Zhejiang Province, China. Case Presentation: A 50-year-old male patient who had Worked as a butcher in a slaughterhouse for 20 years. Admitted to the hospital due to abdominal pain, joint pain, fever, and headache.His condition rapidly worsened causing altered consciousness, drowsiness and developed hearing loss. S. suis induced pyogenic meningitis complicated by arthritis was suspected based on the results of biochemical and culture analysis of the cerebrospinal fluid, and metagenomic next-generation sequencing, The patient's symptoms significantly improved after treatment with antibiotics such as ceftriaxone, meropenem, and linezolid, as well as supportive therapies including steroids and hyperbaric oxygen therapy, and his hearing improved significantly.After about 2 years of follow-up, the hearing was significantly better than before, but hearing impairment still remained. Conclusion: Streptococcus suis is endemic in pork-consuming and pig-raising countries, but can occur throughout the world, especially among individuals with occupational exposure to pigs and/or pork, such as slaughterhouse workers, butchers, farmers, etc. Strengthen science education among key groups. This case was diagnosed as Streptococcus suis meningitis combined with arthritis. However, abdominal pain in the early stage of the disease is very rare and is easy to be misdiagnosed. It is necessary to identify whether it is complicated by peritonitis. For hearing loss caused by Streptococcus suis infection, the use of hyperbaric oxygen chamber treatment has obvious therapeutic effects.

Congenital heart disease detection by pediatric electrocardiogram based deep learning integrated with human concepts.

Early detection is critical to achieving improved treatment outcomes for child patients with congenital heart diseases (CHDs). Therefore, developing effective CHD detection techniques using low-cost and non-invasive pediatric electrocardiogram are highly desirable. We propose a deep learning approach for CHD detection, CHDdECG, which automatically extracts features from pediatric electrocardiogram and wavelet transformation characteristics, and integrates them with key human-concept features. Developed on 65,869 cases, CHDdECG achieved ROC-AUC of 0.915 and specificity of 0.881 on a real-world test set covering 12,000 cases. Additionally, on two external test sets with 7137 and 8121 cases, the overall ROC-AUC were 0.917 and 0.907 while specificities were 0.937 and 0.907. Notably, CHDdECG surpassed cardiologists in CHD detection performance comparison, and feature importance scores suggested greater influence of automatically extracted electrocardiogram features on CHD detection compared with human-concept features, implying that CHDdECG may grasp some knowledge beyond human cognition. Our study directly impacts CHD detection with pediatric electrocardiogram and demonstrates the potential of pediatric electrocardiogram for broader benefits.

OXCT1 regulates hippocampal neurogenesis and alleviates cognitive impairment via the Akt/GSK-3ß/ß-catenin pathway after subarachnoid hemorrhage.

BACKGROUND: Subarachnoid hemorrhage (SAH) is a life-threatening neurological disease that usually has a poor prognosis. Neurogenesis is a potential therapeutic target for brain injury. Ketone metabolism also plays neuroprotective roles in many neurological disorders. OXCT1 (3-Oxoacid CoA-Transferase 1) is the rate-limiting enzyme of ketone body oxidation. In this study, we explored whether increasing ketone oxidation by upregulating OXCT1 in neurons could promote neurogenesis after SAH, and evaluated the potential mechanism involved in this process. METHODS: The ß-hydroxybutyrate content was measured using an enzymatic colorimetric assay. Adeno-associated virus targeting neurons was injected to overexpress OXCT1, and the expression and localization of proteins were evaluated by western blotting and immunofluorescence staining. Adult hippocampal neurogenesis was evaluated by dual staining with doublecortin and 5-Ethynyl-2'-Deoxyuridine. LY294002 was intracerebroventricularly administered to inhibit Akt activity. The Morris water maze and Y-maze tests were employed to assess cognitive function after SAH. RESULTS: The results showed that OXCT1 expression and hippocampal neurogenesis significantly decreased in the early stage of SAH. Overexpression of OXCT1 successfully increased hippocampal neurogenesis via activation of Akt/GSK-3ß/ß-catenin signaling and improved cognitive function, both of which were reversed by administration of LY294002. CONCLUSIONS: OXCT1 regulated hippocampal ketone body metabolism and increased neurogenesis through mechanisms mediated by the Akt/GSK-3ß/ß-catenin pathway, improving cognitive impairment after SAH.

Effectiveness and safety of cefotaxime combined with avibactam for treating multidrug-resistant E coli infections: A systematic review and meta-analysis.

BACKGROUND: Multidrug-resistant Escherichia coli infections are a global health challenge, notably in North America, Europe, Asia, and Africa. This systematic review and meta-analysis evaluates the effectiveness and safety of cefotaxime combined with avibactam, aiming to mitigate these infections' impact and lessen their burden on healthcare systems worldwide. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and PICO frameworks, we conducted a comprehensive literature search across 4 primary databases on May 6, 2023. Studies evaluating the efficacy and safety of cefotaxime and avibactam were included. Key outcomes included treatment success, adverse effects, and microbiological eradication. Quality assessment utilized the Cochrane Collaboration Risk of Bias instrument. Heterogeneity was analyzed using chi-square statistics and the I2 index. Both fixed- and random-effects models were applied as appropriate. Publication bias was rigorously evaluated using Egger linear regression test and funnel plot analysis, ensuring the study's integrity and reliability. RESULTS: The clinical cure rate derived from 8 studies showed no significant difference between the treatment groups (odds ratio [OR] = 1.97, 95% CI: 0.69 to 1.36, P = .86). Analysis of the bacterial clearance rate from the 5 studies also indicated no significant difference (OR = 0.97, 95% CI: 0.42 to 2.25, P = .36). Notably, a reduced mortality rate favoring the experimental group was observed in 6 studies (OR = 0.64, 95% CI: 0.44 to 0.92, P = .012). Comprehensive sensitivity analyses and the assessment of publication bias strengthened the reliability of the results. CONCLUSIONS: Ceftazidime combined with avibactam significantly reduced mortality among patients with multidrug-resistant Escherichia coli infections, indicating its potential as a therapeutic option, especially for carbapenem-resistant Enterobacteriaceae. However, extensive large-scale clinical trials are required to validate these findings.

Astrocyte-derived hepcidin aggravates neuronal iron accumulation after subarachnoid hemorrhage by decreasing neuronal ferroportin1.

Iron accumulation is one of the most essential pathological events after subarachnoid hemorrhage (SAH). Ferroportin1 (FPN1) is the only transmembrane protein responsible for exporting iron. Hepcidin, as the major regulator of FPN1, is responsible for its degradation. Our study investigated how the interaction between FPN1 and hepcidin contributes to iron accumulation after SAH. We found that iron accumulation aggravated after SAH, along with decreased FPN1 in neurons and increased hepcidin in astrocytes. After knocking down hepcidin in astrocytes, the neuronal FPN1 significantly elevated, thus attenuating iron accumulation. After SAH, p-Smad1/5 and Smad4 tended to translocate into the nucleus. Moreover, Smad4 combined more fragments of the promoter region of Hamp after OxyHb stimulation. By knocking down Smad1/5 or Smad4 in astrocytes, FPN1 level restored and iron overload attenuated, leading to alleviated neuronal cell death and improved neurological function. However, the protective role disappeared after recombinant hepcidin administration. Therefore, our study suggests that owing to the nuclear translocation of transcription factors p-Smad1/5 and Smad4, astrocyte-derived hepcidin increased significantly after SAH, leading to a decreased level of neuronal FPN1, aggravation of iron accumulation, and worse neurological outcome.