Long-term exposure to advanced lipid peroxidation end products impairs cognitive function through microbiota-gut-brain axis.

The frequent intake of ultra-processed, heat-processed, and fat-enriched foods rich in dietary advanced lipoxidation end-products (ALEs) has been correlated with cognitive decline; however, the underlying mechanisms of action remain unexplored. This study investigated the impact of a 12-month dietary exposure to ALEs on learning, memory, and Aß1-42 accumulation in mice, with a focus on the AMPK/SIRT1 signaling pathway and ADAM10 expression. The gut microbiota and metabolomic profiles revealed ALEs-induced gut dysbiosis and cognitive impairment, highlighting modulation through the microbiota-gut-brain axis. Key findings include increased pathogenic bacteria and decreased beneficial bacteria, linked to metabolite profile changes that affect neurotoxic Aß1-42 peptide accumulation. This long-term comprehensive study underscores the need for dietary guidelines to reduce ALE intake and mitigate neurodegenerative disease risk, highlighting the intricate interplay between diet, gut microbiota, and cognitive health.

Psychological interventions for social anxiety disorder in children and adolescents: A systematic review and network meta-analysis.

BACKGROUND: Social anxiety disorder (SAD) is a high-prevalence mental disorder among children and adolescents. The aim of this study is to compare and rank the effectiveness of several psychotherapies for SAD among children and adolescents. METHODS: Only randomized controlled trials (RCTs) were utilized by searching PubMed, Embase, Cochrane Library, and Web of Science. We used network meta-analysis in the Bayesian framework to analyze the data. This study is registered with PROSPERO, number CRD42023476829. RESULTS: In total, 30 RCTs with 1547 individuals were included, and nine psychotherapies with three control conditions were compared and ranked in this study. The findings revealed that internet-delivered cognitive behavioural therapy (surface under the cumulative ranking curve [SUCRA: 71.2 %]), group cognitive behavioural therapy (SUCRA: 68.4 %), and individual cognitive behavioural therapy (SUCRA: 66.0 %) significantly reduced social anxiety symptoms; internet-delivered cognitive behavioural therapy also significantly decreased depression symptoms in these patients (SUCRA: 92.2 %). In addition, group cognitive behavioural therapy can enhance functioning in these patients (SUCRA: 89.6 %). CONCLUSION: These results suggest that internet-delivered cognitive behavioural therapy is the optimal type of psychotherapy for reducing social anxiety and depression symptoms in children and adolescents with SAD, internet-delivered parent-child interaction therapy and cognitive bias modification of interpretation have relatively poor treatment effects on social anxiety symptoms in children than other psychological interventions, and group cognitive behavioural therapy has better benefits in enhancing the functioning among children and adolescents with SAD. Further studies are needed to ascertain these results due to the limited number of included studies.

Inhibition of glycosphingolipid synthesis with eliglustat in combination with immune checkpoint inhibitors in advanced cancers: preclinical evidence and phase I clinical trial.

Glycosphingolipids (GSLs) are abundantly expressed in cancer cells. The effects of GSL-targeted immunotherapies are not fully understood. Here, we show that the inhibition of GSL synthesis with the UDP-glucose ceramide glucosyltransferase inhibitor eliglustat can increase the exposure of the major histocompatibility complex (MHC) and tumour antigen peptides, enhancing the antitumour response of CD8+ T cells in a range of tumour models. We therefore conducted a proof-of-concept phase I trial on the combination of eliglustat and an anti-PD-1 antibody for the treatment of advanced cancers (NCT04944888). The primary endpoints were safety and feasibility, and the secondary endpoint was antitumor activity. All prespecified endpoints were met. Among the 31 enrolled patients, only 1 patient experienced a grade 3 adverse event (AE), and no grade 4 AEs were observed. The objective response rate was 22.6% and the disease control rate reached 71%. Of the 8 patients with proficient mismatch repair/microsatellite stable (pMMR/MSS) colorectal cancer, one achieved complete response and two each had partial response and stable disease. In summary, inhibiting the synthesis of GSLs might represent an effective immunotherapy approach.

A shape memory cationized chitosan sponge loaded with thrombin for high-effective hemostasis and antibacterial activity.

This study presents a thrombin-loaded cationized chitosan (TCCS) sponge with highly effective hemostatic and antibacterial activity. The TCCS sponge, prepared using a multistep method, features a porous structure, favorable mechanical properties, excellent water absorption ability, and shape recovery triggered by water or blood. The TCCS sponge exhibited strong antibacterial activity against Methicillin-resistant Staphylococcus aureus and Escherichia coli. Additionally, it demonstrated enhanced procoagulant and hemostatic efficacy in rat tail amputation and rat liver perforation wound models compared to commercial hemostats. Furthermore, the sponge exhibited favorable biocompatibility and biosafety. These findings suggest that the TCCS sponge has substantial potential for practical applications in managing severe hemorrhages and bacterial infections.

Preoperative administration of camrelizumab combined with chemotherapy for borderline resectable esophageal squamous cell carcinoma (BRES-1): study protocol of a single-arm, open-label, phase II study.

Background: The prognosis and first-line treatment response of patients with borderline resectable esophageal squamous cell carcinoma (ESCC) are unsatisfactory. We are conducting the borderline resectable esophageal squamous (BRES-1) study to evaluate the safety and efficacy of camrelizumab combined with chemotherapy in patients with borderline resectable ESCC. Methods: A total of 30 patients with borderline resectable ESCC will be enrolled in the BRES-1 study. These patients will undergo three stages of treatment: neoadjuvant therapy, surgery, and adjuvant therapy. Preoperative therapies will include camrelizumab, cisplatin, and nab-paclitaxel. Preoperative therapies will include camrelizumab, which will be given every 3 weeks for 6 weeks at a dose of 200 mg (baseline weight <50 kg, 3 mg/kg), nab-paclitaxel (130 mg/m2 on days 1 and 8 of one period with 21 days, a total of two cycles), and cisplatin (75 mg/m2 on day 1 of one period with 21 days, a total of two cycles). Patients will undergo esophagectomy 3-6 weeks after completing the neoadjuvant treatment. Three weeks after surgery, camrelizumab combined with chemotherapy will continue to be used for two cycles of maintenance therapy. Then, only camrelizumab will be administered for an entire year. The primary endpoint of this study will be pathological complete response (pCR). Discussion: The BRES-1 trial will evaluate the efficacy and safety of camrelizumab combined with chemotherapy for patients with borderline resectable ESCC. Translational research will explore perioperative complications and drug-related adverse events (AEs). Trial Registration: ChiCTR, ChiCTR2200056728. Registered 11 February 2022. https://www.chictr.org.cn/index.aspx.

Optical fiber integrated WGM cylindrical cavity resonator.

Whispering gallery mode (WGM) resonators are usually discrete optical devices, which have integration difficulties with an optical fiber system. Here we present a new, to the best of our knowledge, type of optical fiber whispering gallery mode resonator based on a cylindrical cavity, which is located in the multimode fiber core and fabricated by femtosecond laser micromachining together with fast hydrofluoric acid etching techniques. When light traveling in the fiber core is tangent to the cylindrical cavity wall, it is coupled into the cavity and circulates along the cavity wall to excite WGM resonance before being coupled out to the same tangential path and continuing propagation in the fiber core. The device is fully integrated into the optical fiber, simple in fabrication, convenient in operation, low in cost, and has a good quality factor (Q) of 1.06 × 104. The device enriches the family of WGM resonators and is expected to have promising applications in photonics.

Study on chemical characterization and sleep-improvement function of Prunella vulgaris L. based on the functional components.

Prunella vulgaris L. (P. vulgaris) has great application value and development prospects in improving sleep. In this study, we continued to evaluate the sleep-improvement function and mechanism of P. vulgaris from both chemical characterization and function based on sleep-improvement functional ingredients, rosmarinic acid and salviaflaside, screened out in the previous stage as the index components. The chemical constituents of P. vulgaris and its phenolic acid fraction were characterized by the UPLC-MSn technology. The quality of the sleep-improvement phenolic acid fraction of P. vulgaris was scientifically evaluated by fingerprints combined with quantitative analysis of rosmarinic acid and salviaflaside. The function of phenolic acid parts of P. vulgaris in improving sleep was verified by different insomnia models including the PCPA-induced insomnia model and surface platform sleep deprivation model. HE staining was used to observe the effect of P. vulgaris on the morphology of nerve cells in different brain regions. In vivo experiments and molecular docking explored the sedative-hypnotic effects of functional ingredients of P. vulgaris. All these results investigated the material basis and mechanism of P. vulgaris to improve sleep from multiple perspectives, which contribute to providing a basis for the development of functional food to improve sleep.

Metal Ion Modulated Electron Transfer in Metalloviologen Compounds: Photochromism and Differentiable Amine Detection.

Different types of electron transfers (ETs) underlie the versatile use of various solid viologen-derived compounds, which is still insufficiently understood and difficult to control. Here, we demonstrate an effective strategy for modulating the key ET process in crystalline metalloviologen compounds (MVCs). By adjusting the coordinated transition metal ions bearing different electronic structures (e.g., d5, d7, d10), three MVCs (i.e., Mn-1, Co-2, and Cd-3) with highly consistent coordination environments have been synthesized successfully. Surprisingly, whether the photochromism (energy-induced ET mechanism) or the specific analyte recognition (molecule-induced ET mechanism), compound Cd-3 exhibits obvious photochromic behavior and differential dimethylamine detection. Combined detailed structural analysis with theoretical calculations, such unique ion-dependent properties, were correlated to the fine modulation of the electron density of the bipyridinium cores by metal ions. Additionally, thanks to the delicate recognition of dimethylamine vapor, a convenient test strip Cd-3-PAN was prepared as a sensitive biogenic amine sensor for evaluating the real-time freshness of seafood.

A predictive model for readmission within 1-year post-discharge in patients with schizophrenia.

BACKGROUND: Schizophrenia is a pervasive and severe mental disorder characterized by significant disability and high rates of recurrence. The persistently high rates of readmission after discharge present a serious challenge and source of stress in treating this population. Early identification of this risk is critical for implementing targeted interventions. The present study aimed to develop an easy-to-use predictive instrument for identifying the risk of readmission within 1-year post-discharge among schizophrenia patients in China. METHODS: A prediction model, based on static factors, was developed using data from 247 schizophrenia inpatients admitted to the Mental Health Center in Wuxi, China, from July 1 to December 31, 2020. For internal validation, an additional 106 patients were included. Multivariate Cox regression was applied to identify independent predictors and to create a nomogram for predicting the likelihood of readmission within 1-year post-discharge. The model's performance in terms of discrimination and calibration was evaluated using bootstrapping with 1000 resamples. RESULTS: Multivariate cox regression demonstrated that involuntary admission (adjusted hazard ratio [aHR] 4.35, 95% confidence interval [CI] 2.13-8.86), repeat admissions (aHR 3.49, 95% CI 2.08-5.85), the prescription of antipsychotic polypharmacy (aHR 2.16, 95% CI 1.34-3.48), and a course of disease ≥ 20 years (aHR 1.80, 95% CI 1.04-3.12) were independent predictors for the readmission of schizophrenia patients within 1-year post-discharge. The area under the curve (AUC) and concordance index (C-index) of the nomogram constructed from these four factors were 0.820 and 0.780 in the training set, and 0.846 and 0.796 for the validation set, respectively. Furthermore, the calibration curves of the nomogram for both the training and validation sets closely approximated the ideal diagonal line. Additionally, decision curve analyses (DCAs) demonstrated a significantly better net benefit with this model. CONCLUSIONS: A nomogram, developed using pre-discharge static factors, was designed to predict the likelihood of readmission within 1-year post-discharge for patients with schizophrenia. This tool may offer clinicians an accurate and effective way for the timely prediction and early management of psychiatric readmissions.

Nitric oxide mediates positive regulation of Nostoc flagelliforme polysaccharide yield via potential S-nitrosylation of G6PDH and UGDH.

Based on our previous findings that salicylic acid and jasmonic acid increased Nostoc flagelliforme polysaccharide yield by regulating intracellular nitric oxide (NO) levels, the mechanism through which NO affects polysaccharide biosynthesis in Nostoc flagelliforme was explored from the perspective of S-nitrosylation (SNO). The addition of NO donor and scavenger showed that intracellular NO had a significant positive effect on the polysaccharide yield of N. flagelliforme. To explore the mechanism, we investigated the relationship between NO levels and the activity of several key enzymes involved in polysaccharide biosynthesis, including fructose 1,6-bisphosphate aldolase (FBA), glucokinase (GK), glucose 6-phosphate dehydrogenase (G6PDH), mitochondrial isocitrate dehydrogenase (ICDH), and UDP-glucose dehydrogenase (UGDH). The enzymatic activities of G6PDH, ICDH, and UGDH were shown to be significantly correlated with the shifts in intracellular NO levels. For further validation, G6PDH, ICDH, and UGDH were heterologously expressed in Escherichia coli and purified via Ni+-NAT affinity chromatography, and subjected to a biotin switch assay and western blot analysis, which revealed that UGDH and G6PDH were susceptible to SNO. Furthermore, mass spectrometry analysis of proteins treated with S-nitrosoglutathione (GSNO) identified the SNO modification sites for UGDH and G6PDH as cysteine 423 and cysteine 249, respectively. These findings suggest that NO modulates polysaccharide biosynthesis in N. flagelliforme through SNO of UGDH and G6PDH. This reveals a potential mechanism through which NO promotes polysaccharide synthesis in N. flagelliforme, while also providing a new strategy for improving the industrial production of polysaccharides.

Association Between Prenatal Exposure to Per- and Poly-Fluoroalkyl Substances From Electronic Waste Disassembly Areas and Steroid Hormones in Human Milk Samples.

Per- and poly-fluoroalkyl substances (PFAS), which are long-lasting environmental contaminants that are released into the environment during the e-waste disassembly process, pose a threat to human health. Human milk is a complex and dynamic mixture of endogenous and exogenous substances, including steroid hormones and PFAS. Therefore, in this study, we aimed to investigate the association between PFAS and steroid hormones in human milk from women living close to an e-waste disassembly area. In 2021, we collected milk samples from 150 mothers within 4 weeks of delivery and analyzed them via liquid chromatography-tandem mass spectrometry to determine the levels of 21 perfluorinated compounds and five steroid hormones (estrone, estriol, testosterone, progesterone, and androstenedione [A-dione]). We also performed multiple linear regression analysis to clarify the association between maternal PFAS exposure and steroid hormone concentrations. Our results indicated that PFOA and PFOS were positively associated with estrone (ß, 0.23; 95% CI, 0.08-0.39) and A-dione (ß, 0.186; 95% CI, 0.016-0.357) concentrations in human milk, respectively. Further, the average estimated daily intake of PFOA and PFOS were 36.5 ng/kg bw/day (range, 0.52-291.7 ng/kg bw/day) and 5.21 ng/kg bw/day (range, 0.26-32.3 ng/kg bw/day), respectively. Of concern, the PFAS intake of breastfeeding infants in the study area was higher than the recommended threshold. These findings suggested that prenatal exposure to PFAS from the e-waste disassembly process can influence steroid hormones levels in human milk. Increased efforts to mitigate mother and infant exposure to environmental pollutants are also required.

The value of diffusion kurtosis imaging and dynamic contrast-enhanced magnetic resonance imaging in the differential diagnosis of parotid gland tumors.

Background: Parotid gland tumors (PGTs) are the most common benign tumors of salivary gland tumors. However, the diagnostic value of relative values of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and diffusion kurtosis imaging (DKI) parameters for PGTs has not been extensively studied. Therefore, this study aimed to evaluate the diagnostic performance of combined DKI and DCE-MRI for differentiating PGTs by introducing the concept of relative value. Methods: The DCE-MRI and DKI imaging data of 142 patients with PGTs between June 2018 and August 2022 were collected. Patients were divided into four groups by histopathology: malignant tumors (MTs), pleomorphic adenomas (PAs), Warthin tumors (WTs), and basal cell adenomas (BCAs). All MRI examinations were conducted using a 3 T MRI scanner with a 20-channel head and neck coil. Quantitative parameters of DCE-MRI and DKI and their relative values were determined. Kruskal-Wallis H test, post-hoc test with Bonferroni correction, one-way analysis of variance (ANOVA) and post-hoc test with least significant difference (LSD) method, and the receiver operating characteristic (ROC) curve were used for statistical analysis. Statistical significance was set at P<0.05. Results: Only the combination of DKI and DCE-MRI parameters could reliably distinguish BCAs from other PGTs. PAs demonstrated the lowest transfer constant from plasma to extravascular extracellular space (Ktrans) value [0.09 (0.06, 0.20) min-1], relative Ktrans (rKtrans) [-0.24 (-0.64, 1.00)], rate constant from extravascular extracellular space to plasma (Kep) value [0.32 (0.22, 0.53) min-1], relative Kep (rKep) [0.32 (0.22, 0.53) min-1], and initial area under curve (iAUC) value [0.15 (0.09, 0.26) mmol·s/kg] compared with WTs, BCAs, and MTs (all P<0.05). The Ktrans values for MTs were substantially lower [0.17 (0.10, 0.31) min-1] than those for WTs (P=0.01). The Kep values for MTs [0.71 (0.52, 1.28) min-1] were substantially lower (all P<0.05) than those for WTs and BCAs. PAs and BCAs had higher diffusion coefficient (D) values and lower diffusion kurtosis (K) values and relative K (rK) values than MTs and WTs. However, the D and K values did not differ significantly even in their relative values of PAs and BCAs (all P>0.05). By using logistic regression, the combination of K value and rKep value further enhanced their discriminatory power between PAs and WTs [area under the ROC curve (AUC), 0.986], the combination of K and rKep value further enhanced their discriminatory power between PAs and MTs (AUC, 0.915), and the combination of D and Kep value further enhanced their discriminatory power between BCAs and MTs (AUC, 0.909). Conclusions: DKI and DCE-MRI can be used to differentiate PGTs quantitatively and can complement each other. The combined use of DKI and DCE-MRI parameters can improve the diagnostic accuracy of distinguishing PGTs.

Prediction of malignant risk stratification model for parotid gland nodules based on clinical and conventional ultrasound features: construction and validation.

Background: Ultrasound is widely used in the examination of the parotid gland, but no single ultrasound feature has demonstrated satisfactory diagnostic performance in predicting the nature of parotid nodules. Unlike the established and widely used grading systems for breast and thyroid nodules, a universally adopted and clinically accepted risk stratification system for malignancy in parotid gland nodules remains absent at present. This study aims to establish a malignant risk stratification model for parotid nodules by analyzing patients' clinical features and conventional ultrasound image characteristics. Methods: In this study, clinical data and ultrasound images of 736 patients with parotid nodules were retrospectively analyzed. Pathological results served as the gold standard, and the patients were randomly divided into training and validation groups in a 7:3 ratio. Clinical and ultrasound features of parotid nodules in the training group were compared. Multifactor logistic regression analysis was employed to screen for risk factors of malignant nodules and quantify scores. The probability of malignant risk was assessed and classified into five grades (Grade 1, normal parotid; Grade 2, definitive benign; Grade 3, possibly benign; Grade 4, suspicious malignant; Grade 5, high probability of malignancy). The diagnostic performance of the model was assessed by using calibration curves, receiver operating characteristic curves, decision curves, and clinical impact curves. Results: Facial symptoms, unclear margin, irregular shape, microcalcification, and abnormal cervical lymph nodes were independent risk factors for malignant parotid nodules. The area under the curve of the model was 0.850 [95% confidence interval (CI): 0.816-0.879] in the training group and 0.846 (95% CI: 0.791-0.891) in the validation group. Conclusions: The malignancy risk stratification model based on clinical and ultrasound image features has a good differentiation between benign and malignant parotid nodules, which is helpful for diagnosis and guiding clinical treatment.

Preoperative Ultrasound Radomics to Predict Posthepatectomy Liver Failure in Patients With Hepatocellular Carcinoma.

PURPOSE: Posthepatectomy liver failure (PHLF) is a major cause of postoperative mortality in hepatocellular carcinoma (HCC) patients. The study aimed to develop a method based on the two-dimensional shear wave elastography and clinical data to evaluate the risk of PHLF in HCC patients with chronic hepatitis B. METHODS: This multicenter study proposed a deep learning model (PHLF-Net) incorporating dual-modal ultrasound features and clinical indicators to predict the PHLF risk. The datasets were divided into a training cohort, an internal validation cohort, an internal independent testing cohort, and three external independent testing cohorts. Based on ResNet50 pretrained on ImageNet, PHLF-Net used a progressive training strategy with images of varying granularity and incorporated conventional B-mode and elastography images and clinical indicators related to liver reserve function. RESULTS: In total, 532 HCC patients who underwent hepatectomy at five hospitals were enrolled. PHLF occurred in 147 patients (27.6%, 147/532). The PHLF-Net combining dual-modal ultrasound and clinical indicators demonstrated high effectiveness for predicting PHLF, with AUCs of 0.957 and 0.923 in the internal validation and testing sets, and AUCs of 0.950, 0.860, and 1.000 in the other three independent external testing sets. The performance of PHLF-Net outperformed models of single- and dual-modal US. CONCLUSIONS: Preoperative ultrasound imaging combining clinical indicators can effectively predict the PHLF probability in patients with HCC. In the internal and external validation sets, PHLF-Net demonstrated its usefulness in predicting PHLF.

Generation of transgenic fish cell line with α-lactalbumin nanocarriers co-delivering Tol2 transposase mRNA and plasmids.

Fish cells, such as grass carp (Ctenopharyngodon idella) kidney (CIK) cells, are harder to transfect than mammalian cells. There is a need for an efficient gene delivery system for fish cells. Here, we used CIK cell line as a model to develop a strategy to enhance RNA and plasmid DNA transfection efficiency using a nanocarrier generated from α-lactalbumin (α-NC). α-NC absorbed nucleic acid cargo efficiently and exhibited low cytotoxicity. Plasmid transfection was more efficient with α-NC than with liposomal transfection reagents. We used α-NC to co-transfect Tol2 transposase mRNA and a plasmid containing Cas9 and GFP, generating a stable transgenic CIK cell line. Genome and RNA sequencing revealed that the Cas9 and GFP fragments were successfully inserted into the genome of CIK cells and efficiently transcribed. In this study, we established an efficient transfection system for fish cells using α-NC, simplifying the process of generating stable transgenic fish cell lines.

A case of multiple soft fibromas complicated with pityriasis versicolor during pregnancy: A case report.

Dermatological conditions in pregnancy pose unique challenges due to concerns for maternal and fetal health. We present a case of a 32-year-old primigravida who, at 36 weeks of gestation, exhibited melanotic papules and neoplasms on her neck, chest, and breasts. Seeking evaluation for potential effects on her unborn child and breastfeeding, she presented to our dermatological outpatient facility. Physical examination revealed varied pigmented papules and verrucous proliferations. Laboratory tests and imaging were unremarkable, with histological analysis confirming fibromas and pityriasis versicolor. The patient declined treatment during pregnancy, and postpartum, spontaneous regression of lesions occurred, with complete resolution within 1 year. The child exhibited normal development, with no recurrence observed at the 2-year follow-up. This case underscores the importance of multidisciplinary care and long-term monitoring in managing dermatological manifestations during pregnancy.

NH2-MXene/OXG nanocomposite hydrogel with efficient photothermal antibacterial activity for potentially removing biofilms.

The adhesion of bacteria to the surface leads to formation of biofilms causing numerous infection problems in implanting medical devices or interventional therapy. Traditional treatment for such problems is generally to administrate patients with antibiotics or antifungal agent. Alternatively, devices are taken out of the body to mechanically destroy the biofilm and re-used by surgery. In this study, a straightforward method was developed to remove biofilms using a MXene-based photothermal hydrogel. The hydrogel consists of dynamic crosslinking network formed by Schiff-base reaction between aldehyde-containing xyloglucan (OXG) and amine-containing MXene (NH2-MXene), which showed efficient killing of both gram-positive Staphylococcus aureus (S. aureus) and gram-negative Escherichia coli (E. coli) bacteria upon near-infrared (NIR) laser irradiation. The NH2-MXene/OXG nanocomposite hydrogel showed a high photothermal antibacterial efficiency and stable photothermal conversion, demonstrated by efficient removal of biofilms ex vivo.

Sirtuin 5-Mediated Desuccinylation of ALDH2 Alleviates Mitochondrial Oxidative Stress Following Acetaminophen-Induced Acute Liver Injury.

Acetaminophen (APAP) overdose is a major cause of drug-induced liver injury. Sirtuins 5 (SIRT5) has been implicated in the development of various liver diseases. However, its involvement in APAP-induced acute liver injury (AILI) remains unclear. The present study aimed to explore the role of SIRT5 in AILI. SIRT5 expression is dramatically downregulated by APAP administration in mouse livers and AML12 hepatocytes. SIRT5 deficiency not only exacerbates liver injury and the inflammatory response, but also worsens mitochondrial oxidative stress. Conversely, the opposite pathological and biochemical changes are observed in mice with SIRT5 overexpression. Mechanistically, quantitative succinylome analysis and site mutation experiments revealed that SIRT5 desuccinylated aldehyde dehydrogenase 2 (ALDH2) at lysine 385 and maintained the enzymatic activity of ALDH2, resulting in the suppression of inflammation and mitochondrial oxidative stress. Furthermore, succinylation of ALDH2 at lysine 385 abolished its protective effect against AILI, and the protective effect of SIRT5 against AILI is dependent on the desuccinylation of ALDH2 at K385. Finally, virtual screening of natural compounds revealed that Puerarin promoted SIRT5 desuccinylase activity and further attenuated AILI. Collectively, the present study showed that the SIRT5-ALDH2 axis plays a critical role in AILI progression and might be a strategy for therapeutic intervention.

Engineering Shewanella oneidensis-Carbon Felt Biohybrid Electrode Decorated with Bacterial Cellulose Aerogel-Electropolymerized Anthraquinone to Boost Energy and Chemicals Production.

Interfacial electron transfer between electroactive microorganisms (EAMs) and electrodes underlies a wide range of bio-electrochemical systems with diverse applications. However, the electron transfer rate at the biotic-electrode interface remains low due to high transmembrane and cell-electrode interfacial electron transfer resistance. Herein, a modular engineering strategy is adopted to construct a Shewanella oneidensis-carbon felt biohybrid electrode decorated with bacterial cellulose aerogel-electropolymerized anthraquinone to boost cell-electrode interfacial electron transfer. First, a heterologous riboflavin synthesis and secretion pathway is constructed to increase flavin-mediated transmembrane electron transfer. Second, outer membrane c-Cyts OmcF is screened and optimized via protein engineering strategy to accelerate contacted-based transmembrane electron transfer. Third, a S. oneidensis-carbon felt biohybrid electrode decorated with bacterial cellulose aerogel and electropolymerized anthraquinone is constructed to boost the interfacial electron transfer. As a result, the internal resistance decreased to 42 Ω, 480.8-fold lower than that of the wild-type (WT) S. oneidensis MR-1. The maximum power density reached 4286.6 ± 202.1 mW m-2, 72.8-fold higher than that of WT. Lastly, the engineered biohybrid electrode exhibited superior abilities for bioelectricity harvest, Cr6+ reduction, and CO2 reduction. This study showed that enhancing transmembrane and cell-electrode interfacial electron transfer is a promising way to increase the extracellular electron transfer of EAMs.

Association between Bilateral Vertebral Artery Blood Flow Changes and Posterior Circulation Infarction in Patients with Severe Intracranial Stenosis.

INTRODUCTION: To explore the association between net vertebral artery flow volume (NVAFV), calculated through color duplex ultrasonography (CDU), and posterior circulation infarction (PCI) in patients with severe intracranial vertebral artery (VA) stenosis. METHODS: 234 patients with severe intracranial VA stenosis (≥70%) were categorized into the PCI group (n=139) and the non-PCI group (n=95) based on cranial MRI diagnosis, The correlation between NVAFV and CT perfusion (CTP) data was analyzed, and the occurrence of PCI under diverse PCI mechanisms was also investigated; Multifactorial logistic regression and Stratified analysis was performed to analyze the association between NVAFV and PCI. Lastly, generalized additive models and smooth curve fitting was utilized to outline relationship between NVAFV and PCI. RESULTS: NVAFV showed a significant correlation with cerebral blood flow (CBF), mean transmit Time (MTT) and time to peak (TTP); In the large artery atherosclerosis mechanism, a reduction in NVAFV correlated with a gradual rise in PCI cases (p = 0.002), while this trend lacked significance in the branch artery occlusive disease mechanism (p = 0.993); In the fully adjusted model, each 10 ml/min increase in NVAFV reduced PCI incidence by 11% (OR 0.890, 95%CI 0.840 to 0.943, p < 0.001), Sensitivity analysis showed similar results; NVAFV presented different PCI risks among various glucose level subgroups, the OR (95%CI) for PCI was 0.788 (0.684, 0.906) in low-glucose group(T1), 0.968 (0.878, 1.066) in moderate-glucose group(T2) and 0.886 (0.801, 0.979) in high-glucose group(T3). Smooth curve fitting demonstrated a linear negative association between NVAFV and PCI. CONCLUSION: NVAFV demonstrated an association with PCI in patients with severe intracranial VA stenosis, it can serve as a reference for identifying high-risk populations of PCI, however, it must be considered in combination with glucose.