High-Throughput Screening of Antioxidant Drug Candidates from Natural Antioxidants with a "Zero" Intrinsic Fluorescence Peroxynitrite Sensing Precursor.

The fluorescence high-throughput screening method is of importance for new antioxidant drug candidate discovery for the treatment of serious hepatorenal syndrome, which displayed an obvious upregulated peroxynitrite level. However, most of the current ONOO- probes possessed incomplete fluorescence quenching efficiency, which can result in non-negligible probe inherent fluorescence. Hence, we utilized the probe conjugated structure disruption strategy to construct hydrogenation phosphorus-substituted rhodamine (H-PRh) with "zero" probe inherent fluorescence character. Based on the precursor, a series of natural products were screened for identifying antioxidant drug candidates. Luteolin was screened out by activating the Sirt1-Nrf2-HO-1 signaling pathway to regulate the accumulation of ONOO- in the hepatorenal syndrome. Overall, the "zero" probe inherent fluorescence ONOO- sensor constructed here applies for a promising and versatile toolbox for illuminating the ONOO--related pathological process in the hepatorenal syndrome. Besides, this strategy of constructing highly sensitive sensors could serve as a valuable reference for further fluorescent probes.

Leadless pacemaker implantation using halo-shape technique in a severe dextroscoliosis octogenarian.

The halo-shape technique (HST) is an emerging approach for implanting a leadless pacemaker in scoliosis patients in recent years. Severe scoliosis and humpback made it challenging to push the tip of the delivery catheter towards the ventricular septum using the conventional gooseneck-shape technique. The feasibility and safety of the use of HST in an octogenarian with severe dextroscoliosis and humpback have not been well-assessed. Here, we report a case of high-degree atrioventricular block octogenarian with severe dextroscoliosis and humpback who successfully received a leadless pacemaker implantation using HST. Procedure-related complications were not observed, and the electrical parameters were stable at 6-month follow-up.

Causal relationships between gut microbiota and polycystic ovarian syndrome: A bidirectional Mendelian randomization study.

INTRODUCTION: Previous studies have established a link between gut microbiota and polycystic ovary syndrome (PCOS), but little is known about their precise causal relationship. Therefore, this study aims to explore whether there are precise causal relationships between gut microbiota and PCOS. MATERIAL AND METHODS: We performed a bidirectional two-sample Mendelian randomization (MR) analysis. Datasets were from the largest published meta-analysis on gut microbiota composition and the FinnGen cohort of the IEU Open Genome-Wide Association Study Project database. Inverse variance weighted (IVW), MR-Egger, constrained maximum likelihood-based Mendelian randomization, weighted median, weighted mode, and simple mode were used. Cochran's Q and MR-Egger intercept tests were employed to measure the heterogeneity. RESULTS: A total of 211 gut microbiota taxa were identified in MR analysis. Nine taxa of bacteria, including Alphaproteobacteria (0.55, 0.30-0.99, p = 0.04), Bacilli (1.76, 1.07-2.91, p = 0.03), Bilophila (0.42, 0.23-0.77, p < 0.01), Blautia (0.16, 0.03-0.79, p = 0.02), Burkholderiales (2.37, 1.22-4.62, p = 0.01), Candidatus Soleaferrea (0.65, 0.43-0.98, p = 0.04), Cyanobacteria (0.51, 0.31-0.83, p = 0.01), Holdemania (0.53, 0.35-0.81, p < 0.01), and Lachnospiraceae (1.86, 1.04-3.35, p = 0.03), were found to be associated with PCOS in the above MR methods included at least IVW method. Cochran's Q statistics and MR-Egger intercept test suggested no significant heterogeneity. In addition, 69 taxa were shown significant for at least the IVW method in reverse MR analysis, of these, 25 had a positive correlation, and 37 had a negative correlation. Additionally, Alphaproteobacteria and Lachnospiraceae (0.95, 0.91-0.98, p < 0.01; 0.97, 0.94-0.99, p = 0.02, respectively) were shown a bidirected causally association with PCOS. CONCLUSIONS: Our study provides evidence of the bidirectional causal association between gut microbiota and PCOS from a genetic perspective.

Liddle Syndrome with a SCNN1A Mutation: A Case Report and Literature Review.

INTRODUCTION: Liddle syndrome is an autosomal dominant monogenic disease that mainly manifests as early-onset hypertension, hypokalaemia and metabolic alkalosis, as well as hyporeninaemia and hypoaldosteronism. The aetiology of Liddle syndrome is missense or frameshift mutations in the SCNN1A, SCNN1B or SCNN1G genes, which encode for the epithelial sodium channel subunits. Among these, mutations in the SCNN1A gene are very rare. Case Presentation Objective: A Liddle syndrome case caused by a SCNN1A mutation was reported from China. A 59-year-old proband had a 21-year history of chronic hypertension. His blood pressure was poorly controlled with various antihypertensive drugs, and hypokalaemia was found 8 years ago with no definite cause. At this visit, the patient presented with excessive renal potassium excretion and decreased renin activity in the postural stimulation test; however, his aldosterone level was normal. METHODS: Subsequent genetic testing identified a missense mutation in SCNN1A (c.1475G ＞ A), which encodes for a protein with an altered amino acid at position 492 (p.Arg492Gln). The pedigree investigation found that the older brother and son of the proband also have the same mutation. The patient's serum potassium returned to normal, and blood pressure control was significantly improved after being treated with triamterene. CONCLUSION: A middle-aged patient with Liddle syndrome was diagnosed. A new point mutation in the SCNN1A gene was detected in this patient, and the pathogenicity of this mutation was predicted using Alphafold software, expanding the genetic mutation spectrum of Liddle syndrome. Genetic testing should be improved to exclude monogenic hypertension in patients with hypertension complicated with hypokalaemia.

CD8+ tissue-resident memory T cells are essential in bleomycin-induced pulmonary fibrosis.

Human tissue-resident memory T (TRM) cells play a crucial role in protecting the body from infections and cancers. Recent research observed increased numbers of TRM cells in the lung tissues of idiopathic pulmonary fibrosis patient. However, the functional consequences of TRM cells in pulmonary fibrosis remain unclear. Here, we found that the numbers of TRM cells, especially the CD8+ subset, were increased in the mouse lung with bleomycin-induced pulmonary fibrosis. Increasing or decreasing CD8+ TRM cells in mouse lungs accordingly altered the severity of fibrosis. In addition, adoptive transfer of CD8+ T cells containing a large number of CD8+ TRM cells from fibrotic lungs was sufficient to induce pulmonary fibrosis in control mice. Treatment with CCL18 to induced CD8+ TRM cell expansion and exacerbated fibrosis, while blocking CCR8 prevented CD8+ TRM recruitment and inhibited pulmonary fibrosis. In conclusion, CD8+ TRM cells are essential for bleomycin-induced pulmonary fibrosis, and targeting CCL18/CCR8/CD8+ TRM cells may be a potential therapeutic approach.

Therapeutic compounds targeting interleukin-1 receptor-associated kinase 4 (IRAK4): an updated patent review (2019 to present).

BACKGROUND: It is more than two decades since IRAK4, a promising target for therapies against various medical conditions, was first reported, but no compounds targeting this enzyme are active on the market or under late-stage clinical development. So it is necessary to continue exploring new and/or improved chemotypes for IRAK4-targeting compounds, to which updated patent reviews are supposed to be of considerable contribution. AREAS COVERED: PCT patents claiming IRAK4-targeting compounds and published through 2019 to present were retrieved, screened and reviewed for the title compounds disclosed therein, where chemotype-specific strategies were adopted for the said reviewing process. Included patents featuring non-Protac compounds were described in terms of generic formulas and variable-indicated moieties of the title compounds, as well as selected title compounds and relevant prior documents. Included patents featuring Protac-based compounds were described in terms of general examples of IRAK-binding moieties and ligase-binding moieties, as well as the presence of conventional linker types. Insights were finally extracted from the patent review. EXPERT OPINION: The last five years has seen a steady increase in the number of PCT patents claiming IRAK4-targeting therapeutic compounds, with some of them being based on new chemotypes and/or discovered by new organizations as potential new players.

Association between depression and vascular aging: a comprehensive analysis of predictive value and mortality risks.

BACKGROUND: Depression is a significant global health concern, projected to become the leading disease burden. Vascular burden has been implicated in the pathogenesis of depression. Conversely, whether depression independently influences the process of vascular aging is unknown. This study aims to investigate the mutual relationship between vascular age and depression. METHODS: Utilizing data from the National Health and Nutrition Examination Survey (NHANES), the study included 27,764 participants after exclusions. Depression was assessed using the Patient Health Questionnaire (PHQ-9). Vascular aging was assessed by estimated pulse wave velocity (ePWV) and the heart age/vascular age (HVA) based on Framingham Risk Score (FRS). The study employed weighted logistic regression and Cox proportional hazards models to analyze the association between vascular age and depression as well as its mortality risk. Mendelian randomization was utilized to explore the causal associations. RESULTS: Individuals with depression exhibited a higher risk of an advanced vascular age over their chronological age. Mendelian randomization analysis indicated a causal relationship between depression and arterial stiffness. A significant association was found between vascular age and depression incidence with odds ratios ranging from 1.10 to 1.38. As vascular age increased, the risk of mortality in individuals with depression increased by 22 % and 46 %, respectively. LIMITATIONS: The study design limits the exploration of the dynamic relationship between changes in vascular age and depression due to the single timepoint measurement. CONCLUSION: This study highlights the bidirectional relationship between depression and vascular age. Vascular age is a significant biomarker for the risk and prognosis of depression, while depression may contribute to vascular aging, which underscores the importance of integrated strategies for managing both vascular health and depression.

Molecular cloning and functional characterization of mitochondrial RNA splicing 2 in fish Megalobrama amblycephala, and its potential roles in magnesium homeostasis and mitochondrial function.

Mitochondrial function can be regulated by ion channels. Mitochondrial RNA splicing 2 (Mrs2) is a magnesium ion (Mg2+) channel located in the inner mitochondrial membrane, thereby mediating the Mg2+ influx into the mitochondrial matrix. However, its potential role in regulating the Mg homeostasis and mitochondrial function in aquatic species is still unclear. This study molecularly characterizes the gene encoding Mrs2 in fish M. amblycephala with its functions in maintaining the Mg homeostasis and mitochondrial function verified. The mrs2 gene is 2133 bp long incorporating a 1269 bp open reading frame, which encodes 422 amino acids. The Mrs2 protein includes two transmembrane domains and a conserved tripeptide Gly-Met-Asn, and has a high homology (65.92-97.64%) with those of most vertebrates. The transcript of mrs2 was relatively high in the white muscle, liver and kidney. The inhibition of mrs2 reduces the expressions of Mg2+ influx/efflux-related proteins, mitochondrial Mg content, and the activities of mitochondrial complex I and V in hepatocytes. However, the over-expression of mrs2 increases the expressions of Mg2+ influx/efflux-related proteins, mitochondrial Mg content, and the complex V activity, but decreases the activities of mitochondrial complex III and IV and citrate synthase in hepatocytes. Collectively, Mrs2 is highly conserved among different species, and is prerequisite for maintaining Mg homeostasis and mitochondrial function in fish.

Retinal ganglion cell complex thickness in subjects with diabetes mellitus and uncontrolled hypertension in China.

PURPOSE: To assess the interactive relationship between blood pressure status and diabetic mellitus (DM) with ganglion cell complex (GCC) thickness in elderly individuals in rural China. METHODS: Participants aged 50 years and older in a rural area of Daxing District, Beijing, were recruited in this study from October 2018 to November 2018. All subjects underwent a comprehensive systemic and ocular examination. Blood pressure status was graded as normotension, controlled hypertension and uncontrolled hypertension according to blood pressure measurements and the use of any medication for hypertension treatment. GCC parameters were measured by spectral-domain optical coherence tomography (SD-OCT). Generalized linear models (GLM) adjusted for related potential confounders were used to assess the interaction between DM and blood pressure status. RESULTS: Among 1415 screened subjects (2830 eyes), a total of 1117 eyes were enrolled in the final analysis. GLM analysis showed a significant interactive relationship between DM with uncontrolled hypertension status (ß = 3.868, p = 0.011). GCC thickness would decrease 0.255 µm per year as the age increased (ß=-0.255, p < 0.001). In a subgroup of 574 subjects with uncontrolled hypertension, DM was associated with an increased average of GCC thickness (ß = 1.929, p = 0.022). CONCLUSIONS: The present results revealed a significant interactive relationship between blood pressure status and DM. The average GCC thickness increased in individuals with DM combined with uncontrolled hypertension, which should be considered in the measurement of GCC. Further studies are warranted to explore ganglion cells changes as a non-invasive method to detect neuron alterations in individuals with DM and uncontrolled hypertension. TRAIL REGISTRATION: The registration number of the present trial in the Chinese Clinical Trial Registry is ChiCTR2000037944.

Correlation between choroidal parameters and primary angle-closure suspect in different age groups.

OBJECTIVE: To investigate the correlations between choroidal parameters and primary angle-closure suspect (PACS) in different age subgroups. METHODS AND ANALYSIS: Participants aged 50 years or older in a rural area of Daxing District, Beijing, were recruited. Swept-source optical coherence tomography was used to measure the choroidal parameters. Demographic, ocular biometry parameters and choroidal parameters were compared between the PACS and non-PACS (NPACS) eyes. Logistic analysis was performed to explore the association between the choroidal parameters and PACS. RESULTS: 192 (26.89%) subjects with PACS and 509 (71.29%) with PACS were analysed. Subjects were divided into two groups: group 1 (50-60 years, n=286) and group 2 (>60 years, n=415). In group 1, the mean subfoveal choroidal thickness of PACS eyes was 341.82±88.23 µm and thicker than NPACS eyes (315.07±83.53 µm, p=0.035). The choroidal volume was greater in PACS eyes (10.61±2.78 mm3) compared with NPACS eyes (9.66±2.49 mm3, p=0.013). In group 2, no significant difference in any choroidal parameters between PACS and NPACS was found. Multivariate regression demonstrated that increased choroidal volume was associated with PACS (OR 1.298, 95% CI 1.117 to 1.510, p<0.001) in group 1. CONCLUSIONS: In the age group of 50-60 years, PACS eyes had greater choroidal thickness and volume than NPACS eyes, and the increased total choroidal volume was a predisposing factor for PACS. TRIAL REGISTRATION NUMBER: ChiCTR2000037944.

Light-Induced Quantum Reconfiguration of Oxyhydroxides for Photoanodes with 4.24% Efficiency and Stability Beyond 250 Hours.

Photoelectrochemical (PEC) water splitting is attracting significant research interest in addressing sustainable development goals in renewable energy. Current state-of-the-art, however, cannot provide photoanodes with simultaneously high efficiency and long-lasting lifetime. Here, large-scale NiFe oxyhydroxides-alloy hybridized co-catalyst layer that exhibits an applied bias photon-to-current efficiency (ABPE) of 4.24% in buried homojunction-free photoanodes and stability over 250 h is reported. These performances represent an increase over the present highest-performing technology by 408% in stability and the most stable competitor by over 330% in efficiency. These results originate from a previously unexplored mechanism of light-induced atomic reconfiguration, which rapidly self-generates a catalytic-protective amorphous/crystalline heterostructure at low biases. This mechanism provides active sites for reaction and insulates the photoanode from performance degradation. Photon-generated NiFe oxyhydroxides are more than 200% higher than the quantity that pure electrocatalysis would otherwise induce, overcoming the threshold for an efficient water oxidation reaction in the device. While of immediate interest in the industry of water splitting, the light-induced NiFe oxyhydroxides-alloy co-catalyst developed in this work provides a general strategy to enhance further the performances and stability of PEC devices for a vast panorama of chemical reactions, ranging from biomass valorization to organic waste degradation, and CO2-to-fuel conversion.

Vonoprazan-amoxicillin dual therapy for Helicobacter pylori eradication in Chinese population: A prospective, multicenter, randomized, two-stage study.

BACKGROUND: The efficacy of Vonoprazan-amoxicillin dual therapy (VAT) in the treatment of Helicobacter pylori (H. pylori) is controversial. AIM: To evaluate the efficacy of VAT in the Chinese population. METHODS: This prospective, multicenter, randomized, open-label, and two-stage study was conducted at 23 centers in Fujian, China (May 2021-April 2022). H. pylori-infected patients were randomized to bismuth quadruple therapy (BQT), BQT-Vonoprazan (BQT-V), seven-day VAT (VAT-7), ten-day VAT (VAT-10), and fourteen-day VAT (VAT-14) groups. The primary endpoint was the H. pylori eradication rate. The secondary endpoint was the frequency of adverse events. This study was registered with the Chinese Clinical Trial Registry, ChiCTR2100045778. RESULTS: In the first stage, VAT-7 and BQT-V groups were selected for early termination because less than 23 among 28 cases were eradicated. In the second stage, the eradication rates for BQT, VAT-10, and VA-14 were 80.2% [95% confidence interval (95%CI): 71.4%-86.8%], 93.2% (86.6%-96.7%), 92.2% (85.3%-96.0%) in the intention-to-treat (ITT) analysis, and 80.9% (95%CI: 71.7%-87.5%), 94.0% (87.5%-97.2%), and 93.9% (87.4%-97.2%) in the per-protocol analysis. The ITT analysis showed a higher eradication rate in the VAT-10 and VAT-14 groups than in the BQT group (P = 0.022 and P = 0.046, respectively). The incidence of adverse events in the VAT-10 and VAT-14 groups was lower than in the BQT group (25.27% and 13.73% vs 37.62%, respectively; P < 0.001). CONCLUSION: VAT with a duration of 10 or 14 days achieves a higher eradication rate than the BQT, with a more tolerable safety profile in H. pylori-infected patients in Fujian.

Acute exacerbation of idiopathic pulmonary fibrosis a narrative review primary focus on treatments.

Background and Objective: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrotic interstitial pneumonia, which is the commonest type of idiopathic interstitial pneumonia in the clinic. For most patients, the course of the disease is slow and prolonged, but a percentage of them develop an acute respiratory worsening during the disease, known as an acute exacerbation of IPF (AE-IPF). The updated guidelines define AE-IPF as an acute worsening of dyspnea in an IPF patient within 1 month and exclude other conditions such as left heart failure and pulmonary embolism. However, the prevention and treatment of AE-IPF are still unclear. Based on the high mortality rate caused by AE, in this article, we will focus on the latest research advances in AE-IPF treatment strategies and provide a comprehensive review of its pathogenesis, risk factors, clinical features, and diagnosis. Methods: This study searched for relevant literature published from 2018 to 2023 in the PubMed database. The search terms used were as follows: "Acute exacerbation", "Idiopathic pulmonary fibrosis", "Biomarker", "Pathogenesis", "Treatment", "HRCT", "Antifibrotic", "Infection", "Immunosuppressant", "Autoantibody", "Oxygen therapy", "Hemoperfusion", "Inflammation". Key Content and Findings: The review found that corticosteroids are still the primary treatment strategy at present, although there is some controversy regarding the dosing and tapering of corticosteroids. However, corticosteroids combined with intravenous cyclophosphamide have been shown to be detrimental to the prognosis of patients with AE-IPF. Given its deadly high mortality rate, early intervention is crucial. Pirfenidone and nintedanib have been proven to reduce incidence of AE. Meanwhile, in the future, the lung microbiome may also be a break-through. Conclusions: This study reviewed the pathogenesis and risk factors of AE-IPF and updated the current and potential treatment strategies regarding AE-IPF. The pathogenesis of AE-IPF is not exact, multiple mechanisms may be involved simultaneously. Corticosteroids remain the mainstream treatment modality in the medical treatment of AE-IFP. Many other treatment modalities have been proposed in succession, but no clear conclusions can be drawn about the effectiveness and safety of these interventions.

Therapeutic drug monitoring of free perampanel concentrations in practice: A practical analytical technique based on centrifugal ultrafiltration sample separation.

Objectives: The centrifugal ultrafiltration-high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was established to determine the free perampanel (PER) concentration in children with epilepsy. Methods: Free PER concentration was obtained using centrifugal ultrafiltration devices. The internal standard was PER-D5. The method was investigated for selectivity, carryover, lower limit of quantification, calibration curve, accuracy, precision, matrix effects, recovery, and stability. The Spearman's correlation coefficient was used to evaluate the correlation between the free and total PER concentrations. A nonparametric test was used to estimate the effects of PER along with other antiepileptic drugs on the total and free PER concentrations. Results: The free PER concentration was positively correlated with the total PER concentration in the 57 plasma samples (r = 0.793 > 0, P < 0.001). Additionally, the free PER concentrations were significantly (P < 0.05) increased in valproic acid (VPA) co-therapy (9.87 ± 5.83) compared with non-VPA co-therapy (5.03 ± 4.57). Conclusions: The proposed method is efficient, sensitive, and suitable for detecting free PER concentrations in children with epilepsy. Simultaneously, the free PER concentration response to clinical outcomes in children with epilepsy was more clinically significant, particularly when combined with VPA.

Xylooligosaccharides alleviate the carbohydrate-enriched diet-induced intestinal barrier dysfunction in carp Megalobrama amblycephala by promoting intestinal development, immunity and gut microbiota.

To date, although the high-carbohydrate (HC) feed has been extensively adopted in the aquaculture industry, its effects on the intestinal function and development of aquatic animals still remain unclear. In addition, the corresponding nutritional intervention is still barely reported. This study aimed to evaluate the influence of xylooligosaccharides (XOS) on the intestinal health of Megalobrama amblycephala subjected to a HC feeding. Fish (average weight: 44.55 ± 0.15 g) were randomly offered 3 diets, including a control one (29 % carbohydrate), a HC one (41 % carbohydrate), and a XOS supplemented one (HC + 1.0 % XOS, HCX) respectively for 12 weeks. The HC feeding caused morphological abnormalities of intestine, an increased intestinal permeability, and the intestinal immunosuppression, all of which were markedly reversed by XOS administration. In addition, compared with the HC group, HCX feeding remarkably promoted the intestinal activities of digestive and brush border enzymes, and the expressions of cell proliferation-related proteins (Wnt10b and Cyclin D1). The 16s rDNA sequencing also revealed that XOS administration increased the abundance of beneficial bacteria, and decreased that of pathogenic ones. In conclusion, dietary supplementation of XOS improved the intestinal histomorphology, barrier function, cell proliferation and bacterial communities of carbohydrate-overloaded fish Megalobrama amblycephala.

Case report: Magnetic resonance imaging findings of patients with diffuse uterine leiomyomatosis.

Background: Diffuse uterine leiomyomatosis (DUL) is a seldom-seen condition, with only a handful of cases of magnetic resonance imaging (MRI) findings documented. In clinical settings, it is often mistaken for multiple uterine leiomyomas due to a lack of adequate recognition of DUL. Objective: This study shows two instances of DUL, underscoring their MRI findings to improve preoperative diagnostic precision. Conclusion: For patients exhibiting multiple uterine leiomyomas with masses present in the parametrial and abdominal cavities, consideration should be given to diagnosing DUL with DPL. The discoveries outlined in this paper furnish insights that can assist in directing treatment choices.

Metformin attenuates high-carbohydrate diet-induced redox imbalance, inflammation, and mitochondrial dysfunction in Megalobrama amblycephala.

This study aimed to investigate the effects of dietary metformin supplementation on the redox balance, inflammation, mitochondrial biogenesis, and function in blunt snout bream fed a high-carbohydrate (HC) diet. Fish (45.12 ± 0.36 g) were randomly offered four diets, including a control diet (33% carbohydrate), an HC diet (45% carbohydrate), and the HC diet supplemented with 0.06% (HCM1) and 0.12% (HCM2) metformin respectively for 12 weeks. Compared with the control, feeding the HC diet significantly increased the hepatosomatic index (HSI), the mesenteric fat index, liver and muscle glycogen contents, liver and adipose tissue lipid contents, plasma glucose and glycation end products (AGES) levels and aspartate transaminase activity, plasma and liver malondialdehyde (MDA) contents, hepatic adenosine triphosphate (ATP) and adenosine monophosphate (AMP) contents, mitochondrial cytochrome c content, mitochondrial complex IV activity and ATP 6 transcription, but decreased plasma catalase (CAT) activity, muscle superoxide dismutase (SOD) activity, hepatic antioxidant enzymes activities, and the transcriptions of transforming growth factor ß (tgfß) and interleukin 10 (il10). Compared with the HC group, metformin treatment (especially the HCM2 group) significantly elevated tissue glycogen contents, muscle SOD activity, plasma and liver antioxidant enzymes activities, the transcriptions of tgfß and il10, the sodium/potassium ATPase activity, the contents of mitochondrial protein and AMP, the level of p-AMP activated protein kinase (AMPK), and the p-AMPK/t-AMPK ratio, but lowered the HSI, tissue lipid contents, plasma levels of glucose, AGES and glycated serum protein, plasma, and liver MDA contents, the transcriptions of il1ß, NADH dehydrogenase subunit 1 and ATP 6, the contents of ATP and cytochrome c, the ATP/AMP ratio, and the activities of complexes I and IV. In conclusion, metformin could attenuate the HC diet-induced redox imbalance, inflammation, and mitochondrial dysfunction in blunt snout bream.

Dual Enzyme-Locked Activation Reporter for Accurate Liver Cancer Surveillance.

Activatable probes with a higher signal-to-background ratio and accuracy are essential for monitoring liver cancer as well as intraoperative fluorescence navigation. However, the presence of only one biomarker is usually not sufficient to meet the high requirement of a signal-to-background ratio in cancer surveillance, leading to the risk of misdiagnosis. In this work, a dual-locked activation response probe, Si-NTR-LAP, for nitroreductase and leucine aminopeptidase was reported. This dual-locked probe provides better tumor recognition and a higher signal-to-noise ratio than that of single-locked probes (Si-LAP and Si-NTR). In both the subcutaneous tumor model and the more complex orthotopic hepatocellular carcinoma model, the probe was able to identify tumor tissue with high specificity and accurately differentiate the boundaries between tumor tissue and normal tissue. Therefore, the dual-locked probe may provide a new and practical strategy for applying to real patient tumor tissue samples.

Long-term outcome of bicuspid aortic valve repair using figure-of-8 hitch-up stitches.

Objective: To maximize successful repair of bicuspid aortic valves by adding figure-of-8 hitch-up stitches at commissures. Methods: From 2000 to 2022, bicuspid aortic valve repair was performed on 1112 patients at Cleveland Clinic, with 367 patients receiving figure-of-8 hitch-up stitches along with classical techniques, including Cabrol suture, cusp plication, raphe resection, and valve-sparing root replacement. Operative outcomes, repair durability, and survival were assessed in the figure-of-8 hitch-up stitches cohort, and outcomes were compared among 195 balancing-score-matched patient pairs who underwent bicuspid aortic valve repair with and without figure-of-8 hitch-up stitches. Results: Patients who underwent bicuspid aortic valve repair with figure-of-8 stitches had an operative mortality of 0.3% (1 of 367) and in-hospital reoperation for aortic valve dysfunction of 1.1% (4 of 367). At 10 years, prevalence of severe aortic regurgitation was 8.6%, mean gradient 24 mm Hg, freedom from aortic valve reoperation 75%, and survival 98%. In matched cohorts, operative mortality was similar (0.51% vs 0%; P > .9) as were morbidities, including in-hospital reoperation due to aortic valve dysfunction (1.0% vs 1.5%; P > .9). Comparable long-term outcomes were observed at 10 years (prevalence of severe aortic regurgitation of 8.7% vs 5.0% [P = .11], mean gradient 18 vs 17 mm Hg [P = .40]; freedom from aortic valve reoperation 80% vs 81% [P = .73]; and survival 99.5% vs 94.6% [P = .18]). Conclusions: Figure-of-8 hitch-up stitch is a safe bicuspid aortic valve repair technique. It increases the likelihood of a successful repair without increasing risk of cusp tear and achieves satisfactory long-term survival and durability when added to classical repair techniques.