PPARß/δ-orchestrated metabolic reprogramming supports the formation and maintenance of memory CD8+ T cells.

The formation of memory T cells is a fundamental feature of adaptative immunity, allowing the establishment of long-term protection against pathogens. Although emerging evidence suggests that metabolic reprogramming is crucial for memory T cell differentiation and survival, the underlying mechanisms that drive metabolic rewiring in memory T cells remain unclear. Here, we found that up-regulation of the nuclear receptor peroxisome proliferator-activated receptor ß/δ (PPARß/δ) instructs the metabolic reprogramming that occurs during the establishment of central memory CD8+ T cells. PPARß/δ-regulated changes included suppression of aerobic glycolysis and enhancement of oxidative metabolism and fatty acid oxidation. Mechanistically, exposure to interleukin-15 and expression of T cell factor 1 facilitated activation of the PPARß/δ pathway, counteracting apoptosis induced by antigen clearance and metabolic stress. Together, our findings indicate that PPARß/δ is a master metabolic regulator orchestrating a metabolic switch that may be favorable for T cell longevity.

Effectiveness of nurse-led non-pharmacological interventions on outcomes of delirium in adults: A meta-analysis of randomized controlled trials.

BACKGROUND: Delirium is a common complication among adults. It is essential to improve the outcomes of delirium. AIM: To systematically synthesize the evidence on the effectiveness of the nurse-led non-pharmacological interventions on outcomes of delirium in adults. METHODS: Electronic databases including CINAHL, Cochrane Library, MEDLINE, EMBASE, PubMed, Web of Science, PsycINFO, and Clinical Trial Registration were searched comprehensively by the authors. The authors reviewed the full text and assessed the risk of bias using the Cochrane Risk of Bias Tool 2.0. The meta-analysis was performed using RevMan and Stata software. The forest plots showed the overall effect of the included study and the I2 test was used to assess the degree of heterogeneity between studies. Random effects models were used to analyze studies with significant heterogeneity. RESULTS: A total of 32 studies (10,122 participants) were included in the meta-analysis. Nurse-led non-pharmacological interventions resulted in a significantly lower incidence of delirium compared with the usual care/control group (risk ratio = 0.74, p < .001) and reduced mortality in the hospital compared with usual care (risk ratio = 0.81, p = .04). However, the implementation of nurse-led, non-pharmacological interventions had no significant effect on the duration, severity of delirium, or length of hospital stay. LINKING EVIDENCE TO ACTION: Our findings suggest that the nurse-led, non-pharmacological strategy was effective in reducing the incidence of delirium and mortality in the hospital. Multicomponent interventions were the most effective strategy for reducing the incidence of delirium in adults.

Role of Decreased Expression of miR-155 and miR-146a in Peripheral Blood of Type 2 Diabetes Mellitus Patients with Diabetic Peripheral Neuropathy.

Objective: To Study the Correlations of microRNA-155 (miR-155) and microRNA-146a (miR-146a) Expression in Peripheral Blood of Type 2 Diabetes Mellitus (T2DM) Patients with Diabetic Peripheral Neuropathy (DPN), and Explore the Clinical Value of miR-155 and miR-146a in the Diagnosis and Treatment Outcomes of DPN. Methods: The study included 51 T2DM patients without DPN (T2DM group), 49 T2DM patients with DPN (DPN group), and 50 normal controls (NC group). Quantitative real-time PCR was utilized to determine the expression levels of miR-155 and miR-146a. Clinical features and risk factors for DPN were assessed. Multivariate stepwise logistic regression analysis was conducted to confirm whether the expressions of miR-155 and miR-146a could independently predict the risk of DPN. ROC curve analysis evaluated their diagnostic value. Results: The T2DM group exhibited significantly lower expression levels of miR-155 and miR-146a compared to the NC group (P < 0.05). Moreover, the DPN group exhibited a significantly decreased expression level of miR-155 and miR-146a compared to the T2DM group (P < 0.01). Multivariate logistic regression analysis indicated that higher levels of miR-155 and miR-146a might serve as protective factors against DPN development. ROC curve analysis revealed that miR-155 (sensitivity 91.8%, specificity 37.3%, AUC 0.641,) and miR-146a (sensitivity 57.1%, specificity 84.3%, AUC 0.722) possess a strong ability to discriminate between T2DM and DPN. Their combined use further enhanced the diagnostic potential of DPN (sensitivity 83.7%, specificity 60.8%, AUC 0.775). A multi-index combination can improve DPN diagnostic efficiency. Conclusion: The decreased expression of miR-155 and miR-146a in the peripheral blood of T2DM patients is closely related to the occurrence of DPN, highlighting their potential as valuable biomarkers for diagnosing and prognosticating DPN.

Safflower polysaccharide ameliorates acute ulcerative colitis by regulating STAT3/NF-κB signaling pathways and repairing intestinal barrier function.

This study is to investigate the effect of SPS on the UC model. An animal model of UC induced by DSS was developed using C57BL/6 mice. The body weight was recorded every day, and the symptoms related to UC were detected. H&E staining, AB-PAS staining and PSR staining were used to evaluate the histopathological changes of the colon. Inflammation and mucosal barrier indicators were detected by qRT-PCR, and the 16 S rRNA sequence was used to detect the intestinal flora. SPS can significantly prevent and treat DSS-induced ulcerative colitis in animals. SPS significantly improved clinical symptoms, alleviated pathological damage, inhibited the infiltration of intestinal inflammatory cells. SPS treatment can protect goblet cells, enhance the expression of tight junction proteins and mucins, inhibit the expression of antimicrobial peptides, thereby improving intestinal barrier integrity. The prevention and treatment mechanism of SPS may be related to the inhibition of STAT3/NF-κB signaling pathway to regulate intestinal barrier function. In particular, SPS also significantly adjusted the structure of intestinal flora, significantly increasing the abundance of Akkermansia and Limosilactobacillus and inhibiting the abundance of Bacteroides. Overall, SPS has a significant therapeutic effect on ulcerative colitis mice, and is expected to play its value effectively in clinical treatment.

Enhanced Fenton-like process over Z-scheme MoO3 surface decorated with Fe2O3 under visible light.

Photocatalysts consisting of Z-scheme heterojunctions are commonly used in wastewater treatment due to their exceptional reactivity in photocatalysis and highly efficient visible-light utilization. In this work, Fe2O3-decorated MoO3 rods were synthesized through a two-step method and their photodegradation of methylene blue (MB) was evaluated. The Fe2O3/MoO3 rods were characterized by XRD, SEM, micro-Raman, XPS, UV-Vis DRS, and PL to investigate their structural, morphological, and optical properties. The results indicate that the photodegradation efficiency of Fe2O3/MoO3 improved through a reduction in the gap energy and persistence of a 1D hexagonal prism structure. The degradation rate of MB was enhanced from 31.7 to 91.5% after irradiation for 180 min owing to electron-hole separation and Fenton-like process. Formation of the OH radical is a key factor in the photodegradation reaction and with the addition of H2O2 the efficiency can further improve via a Fenton-like mechanism. Furthermore, the Z-scheme mechanism concurrently delineated. The Fe2O3/MoO3 rod composites were also found to retain high photocatalytic efficiency after being reused five times, which may be useful for future applications.

Lactate drives CD38 signaling to promote Epithelial-Mesenchymal Transition through Snail induction in non-small cell lung cancer cells.

CD38 is the main NADase in mammalian cells. It regulates the homeostasis of nicotinamide adenine dinucleotide (NAD+) and extracellular nucleotides. Its function plays an important role in infection and aging. However, its potential functions in tumor cells have not been fully elucidated. In the present study, we demonstrated that lactate, which is derived from tumor metabolism remodeling, upregulates the expression of CD38 through OXPHOS-driven Hippo-TAZ pathway. The highly expressed CD38 converts NAD + to adenosine through the CD203a/CD73 complex and adenosine binds and activates its receptor A2AR, inducing the expression of Snail and promoting the invasion and metastasis of lung cancer cells. This finding elucidates a new perspective on the interplay between NAD + metabolism and glycolysis in tumor development.

Immunometabolic features of natural killer cells are associated with infection outcomes in critical illness.

Immunosuppression increases the risk of nosocomial infection in patients with chronic critical illness. This exploratory study aimed to determine the immunometabolic signature associated with nosocomial infection during chronic critical illness. We prospectively recruited patients who were admitted to the respiratory care center and who had received mechanical ventilator support for more than 10 days in the intensive care unit. The study subjects were followed for the occurrence of nosocomial infection until 6 weeks after admission, hospital discharge, or death. The cytokine levels in the plasma samples were measured. Single-cell immunometabolic regulome profiling by mass cytometry, which analyzed 16 metabolic regulators in 21 immune subsets, was performed to identify immunometabolic features associated with the risk of nosocomial infection. During the study period, 37 patients were enrolled, and 16 patients (43.2%) developed nosocomial infection. Unsupervised immunologic clustering using multidimensional scaling and logistic regression analyses revealed that expression of nuclear respiratory factor 1 (NRF1) and carnitine palmitoyltransferase 1a (CPT1a), key regulators of mitochondrial biogenesis and fatty acid transport, respectively, in natural killer (NK) cells was significantly associated with nosocomial infection. Downregulated NRF1 and upregulated CPT1a were found in all subsets of NK cells from patients who developed a nosocomial infection. The risk of nosocomial infection is significantly correlated with the predictive score developed by selecting NK cell-specific features using an elastic net algorithm. Findings were further examined in an independent cohort of COVID-19-infected patients, and the results confirm that COVID-19-related mortality is significantly associated with mitochondria biogenesis and fatty acid oxidation pathways in NK cells. In conclusion, this study uncovers that NK cell-specific immunometabolic features are significantly associated with the occurrence and fatal outcomes of infection in critically ill population, and provides mechanistic insights into NK cell-specific immunity against microbial invasion in critical illness.

A versatile CuCo@PDA nanozyme-based aptamer-mediated lateral flow assay for highly sensitive, on-site and dual-readout detection of Aflatoxin B1.

Mycotoxin contaminations in food and environment seriously harms human health. Constructing sensitive and point-of-test early-warning tools for mycotoxin determination is in high demand. In this study, a CuCo@PDA nanozyme-based aptamer-mediated lateral flow assay (Apt-LFA) has been elaborately designed for on-site and sensitive determination of mycotoxin Aflatoxin B1 (AFB1). Benefiting from the rich functional groups and excellent peroxidase-like activity, the CuCo@PDA with original dark color can be conjugated with the specific recognition probe (i.e., aptamer), generating colorimetric signal on the test lines of Apt-LFA via a competitive sensing strategy. The signal can further be amplified in-situ by catalytic chromogenic reaction. Therefore, a visual and dual-readout detection of AFB1 has been realized. The developed Apt-LFA provides a flexible detection mode for qualitative and quantitative analysis of AFB1 by naked-eyes observation or smartphone readout. The smartphone-based LFA platform shows a reliable and ultrasensitive determination of AFB1 with the limit of detection (LOD) of 2.2 pg/mL. The recoveries in the real samples are in the range of 95.11-113.77% with coefficients of variations less than 9.84%. This study provides a new approach to realize point-of-test and sensitive detection of mycotoxins in food and environment using nanozyme-based Apt-LFAs.

Phellinus merrillii extracts induce apoptosis of vascular smooth muscle cells via intrinsic and extrinsic pathways.

Restenosis frequently occurs after balloon angioplasty. Percutaneous coronary intervention (PCI)-induced artery damage is a significant part of triggering restenosis of the vascular smooth muscles (VSMC). This study aimed to study how ethanol extract of Phellinus merrillii (EPM) affected balloon injury-induced overgrowth of VSMC, indicating neointima formation. Firstly, our results demonstrated that EPM notably decreased VSMC viability. A fragmentation assay and Annexin V/Propidium Iodide apoptosis assay showed that higher doses of EPM significantly induced the apoptosis of VSMC after 24 h of exposure. Total protein extracted from VSMC treated with EPM in various time and concentration periods was then conducted in Western blotting analysis. Our data demonstrated that EPM substantially elevated the p53, p21, Fas, Bax, p-p38, and active caspase-3 protein expressions. The results indicated that EPM induces VSMC apoptosis via intrinsic and extrinsic pathways. Also, our results demonstrated that EPM effectively attenuated the balloon injury-induced neointima formation. In conclusion, the information offers a mechanism of EPM in inducing the VSMC apoptosis, thus as a potential interference for restenosis.

Effect of Hypoglycemic Drugs on Kisspeptin Expression in the Hypothalamic Arcuate Nucleus of PCOS Rats.

Background: To investigate the change in hypothalamic kisspeptin-1 (Kiss1) expression during the development of polycystic ovary syndrome (PCOS) and hypoglycemic drug intervention. Methods: Letrozole lavage was used to construct a polycystic ovary rat model. After successful modeling, we treated PCOS rats with metformin, pioglitazone, and acarbose, and we then observed changes in weight, estrus, glucose tolerance, insulin resistance, sex hormones, and hypothalamic kiss1 expression. Results: PCOS rats exhibited increased body weight, abnormal estrous cycle, impaired glucose tolerance, insulin resistance, increased testosterone level, increased luteinizing hormone level, and increased Kiss1 expression in the hypothalamus. However, intervention with metformin, pioglitazone, and acarbose improved the reproductive and metabolic disorders as well as reduced hypothalamic Kiss1 expression. Conclusion: The expression of hypothalamic Kiss1 may play an important role in the pathogenesis of PCOS. Metformin, pioglitazone, and acarbose may reduce the expression of hypothalamic Kiss1 by improving insulin resistance, thereby improving reproductive and metabolic disorders in PCOS rats.

Is use of a long-term proton pump inhibitor or histamine-2 receptor antagonist a risk factor for iron-deficiency anaemia in Taiwan? A neglected clinical drug-drug interaction.

BACKGROUND: Proton pump inhibitors (PPIs) and histamine-2 receptor (H2) antagonists change the gastric pH and reduce the intestinal absorption of nonheme iron. Case reports and case-control studies have demonstrated that absorption of iron is affected by gastric acidity, but the clinical importance of these drug-drug interactions has remained uncertain. OBJECTIVES: The present case-control study employed 2 million longitudinal claims in 2011-2018 in the Taiwan National Health Insurance Research Database to investigate the impact of PPIs/H2 antagonists on the occurrence of iron-deficiency anaemia (IDA). METHODS: The present study retrospectively compared exposure to PPIs/H2 antagonists for 1 year among 5,326 cases with IDA and 21,304 matched controls. The postdiagnosis prescribing pattern was also calculated to understand current practice. RESULTS: Long-term (≥2 month) use of PPIs/H2 antagonists resulted in a higher risk of developing IDA than noncontinuous use/nonuse of those drugs (adjusted odds ratio [aOR] = 2.36, 95% confidence interval [CI] = 1.94-2.86, P < 0.001). There were significant changes in the postdiagnosis prescribing patterns of PPIs/H2 antagonists. The risk of developing IDA remained significant in the female subgroup (aOR = 2.16, 95% CI = 1.73-2.70, P < 0.001) and was even more prominent in those aged ≥ 50 years (aOR = 2.68, 95% CI = 1.94-3.70, P < 0.05). CONCLUSIONS: This study found that long-term use of PPIs/H2 antagonists increased the risk of developing IDA, and there was strong evidence of prescription pattern adjustments postdiagnosis. Physicians and pharmacists should be aware of this risk when patients are expected to take or have been taking PPIs/H2 antagonists for the long term.

Proton pump inhibitors (PPIs) and histamine-2 receptor (H2) antagonists, 2 kinds of gastric suppressants commonly used for gastroesophageal reflux disease, decrease iron absorption in the gut and thus increase the risk of developing iron-deficiency anaemia (IDA). We constructed a retrospective matched case-control study within the Taiwan National Health Insurance Research Database. The longer period of PPIs/H2 antagonists used, the higher risk of IDA was, with the highest risk in female elderly groups (adjusted odds ratio = 2.68 in females aged ≥ 50). PPI users had a higher risk than H2 antagonist users during the 1-year follow-up. The prescription patterns postdiagnosis of IDA witnessed considerable drops for both groups, with less than a 10th of original users remaining the usages (1.72% and 9.85% taking PPIs and H2 antagonists within 90 days after receiving a diagnosis, respectively). Physicians and pharmacists should be aware of the risk of developing IDA in patients currently undergoing or expected to take long-term gastric acid suppressants.

Targeting pathogenic macrophages by the application of SHP-1 agonists reduces inflammation and alleviates pulmonary fibrosis.

Idiopathic pulmonary fibrosis is a progressive fibrotic disorder with no cure that is characterized by deterioration of lung function. Current FDA-approved drugs for IPF delay the decline in lung function, but neither reverse fibrosis nor significantly improve overall survival. SHP-1 deficiency results in hyperactive alveolar macrophages accumulating in the lung, which contribute to the induction of pulmonary fibrosis. Herein, we investigated whether employing a SHP-1 agonist ameliorates pulmonary fibrosis in a bleomycin-induced pulmonary fibrosis murine model. Histological examination and micro-computed tomography images showed that SHP-1 agonist treatment alleviates bleomycin-induced pulmonary fibrosis. Reduced alveolar hemorrhage, lung inflammation, and collagen deposition, as well as enhanced alveolar space, lung capacity, and improved overall survival were observed in mice administered the SHP-1 agonist. The percentage of macrophages collected from bronchoalveolar lavage fluid and circulating monocytes in bleomycin-instilled mice were also significantly reduced by SHP-1 agonist treatment, suggesting that the SHP-1 agonist may alleviate pulmonary fibrosis by targeting macrophages and reshaping the immunofibrotic niche. In human monocyte-derived macrophages, SHP-1 agonist treatment downregulated CSF1R expression and inactivated STAT3/NFκB signaling, culminating in inhibited macrophage survival and perturbed macrophage polarization. The expression of pro-fibrotic markers (e.g., MRC1, CD200R1, and FN1) by IL4/IL13-induced M2 macrophages that rely on CSF1R signaling for their fate-determination was restricted by SHP-1 agonist treatment. While M2-derived medium promoted the expression of fibroblast-to-myofibroblast transition markers (e.g., ACTA2 and COL3A1), the application of SHP-1 agonist reversed the transition in a dose-dependent manner. Our report indicates that pharmacological activation of SHP-1 ameliorates pulmonary fibrosis via suppression of CSF1R signaling in macrophages, reduction of pathogenic macrophages, and the inhibition of fibroblast-to-myofibroblast transition. Our study thus identifies SHP-1 as a druggable target for the treatment of IPF, and suggests that the SHP-1 agonist may be developed as an anti-pulmonary fibrosis medication that both suppresses inflammation and restrains fibroblast-to-myofibroblast transition.

Explainable Machine Learning Techniques To Predict Amiodarone-Induced Thyroid Dysfunction Risk: Multicenter, Retrospective Study With External Validation.

BACKGROUND: Machine learning offers new solutions for predicting life-threatening, unpredictable amiodarone-induced thyroid dysfunction. Traditional regression approaches for adverse-effect prediction without time-series consideration of features have yielded suboptimal predictions. Machine learning algorithms with multiple data sets at different time points may generate better performance in predicting adverse effects. OBJECTIVE: We aimed to develop and validate machine learning models for forecasting individualized amiodarone-induced thyroid dysfunction risk and to optimize a machine learning-based risk stratification scheme with a resampling method and readjustment of the clinically derived decision thresholds. METHODS: This study developed machine learning models using multicenter, delinked electronic health records. It included patients receiving amiodarone from January 2013 to December 2017. The training set was composed of data from Taipei Medical University Hospital and Wan Fang Hospital, while data from Taipei Medical University Shuang Ho Hospital were used as the external test set. The study collected stationary features at baseline and dynamic features at the first, second, third, sixth, ninth, 12th, 15th, 18th, and 21st months after amiodarone initiation. We used 16 machine learning models, including extreme gradient boosting, adaptive boosting, k-nearest neighbor, and logistic regression models, along with an original resampling method and 3 other resampling methods, including oversampling with the borderline-synthesized minority oversampling technique, undersampling-edited nearest neighbor, and over- and undersampling hybrid methods. The model performance was compared based on accuracy; Precision, recall, F1-score, geometric mean, area under the curve of the receiver operating characteristic curve (AUROC), and the area under the precision-recall curve (AUPRC). Feature importance was determined by the best model. The decision threshold was readjusted to identify the best cutoff value and a Kaplan-Meier survival analysis was performed. RESULTS: The training set contained 4075 patients from Taipei Medical University Hospital and Wan Fang Hospital, of whom 583 (14.3%) developed amiodarone-induced thyroid dysfunction, while the external test set included 2422 patients from Taipei Medical University Shuang Ho Hospital, of whom 275 (11.4%) developed amiodarone-induced thyroid dysfunction. The extreme gradient boosting oversampling machine learning model demonstrated the best predictive outcomes among all 16 models. The accuracy; Precision, recall, F1-score, G-mean, AUPRC, and AUROC were 0.923, 0.632, 0.756, 0.688, 0.845, 0.751, and 0.934, respectively. After readjusting the cutoff, the best value was 0.627, and the F1-score reached 0.699. The best threshold was able to classify 286 of 2422 patients (11.8%) as high-risk subjects, among which 275 were true-positive patients in the testing set. A shorter treatment duration; higher levels of thyroid-stimulating hormone and high-density lipoprotein cholesterol; and lower levels of free thyroxin, alkaline phosphatase, and low-density lipoprotein were the most important features. CONCLUSIONS: Machine learning models combined with resampling methods can predict amiodarone-induced thyroid dysfunction and serve as a support tool for individualized risk prediction and clinical decision support.

Hollow NiCo@C Nanozyme-Embedded Paper-Based Colorimetric Aptasensor for Highly Sensitive Antibiotic Detection on a Smartphone Platform.

Antibiotic residues in the environment and in foods pose a serious threat to ecosystems and human health. Developing sensitive and on-site detection methods is therefore in high demand. In this work, a portable paper-based colorimetric sensor with a smartphone platform with an ultrahigh sensitivity has been designed for on-site and quantitative analysis of antibiotic residues based on aptamer-regulated nanozyme activity. The developed excellent peroxidase-like nanozymes, carbon-protected NiCo bimetal oxides with a unique hollow nanocage structure (NiCo@C HCs), could effectively catalyze the oxidation of chromogenic substrates by H2O2. Once bound to a specific aptamer, the enzyme-mimicking activity of NiCo@C HCs is obviously inhibited as a result of the masking of active sites but could be restored via the target-aptamer recognition. Herein, the aptamer-modified NiCo@C HCs are embedded on paper pieces to construct paper-based biochips for visual detection. Meanwhile, a smartphone platform is integrated for the signal readout. Using enrofloxacin (ENR) as an analyte model, the proposed paper-based analysis platform shows a reliable and sensitive detection of ENR with an ultralow detection limit of 0.029 ng/mL. The platform also works well in various real samples. This analysis method is facile in design, showing a great application potential for on-site and mass screening of antibiotic residues in the environment and in foods.

Rheological Characterization and Accumulation Tests for Strong Thixotropic Engineering Slurry.

Underground void subsidence hazards, especially mine goaf, have now become one of the major social problems affecting the well-being of civilians and development in China. The objective of this study was to propose a kind of strong thixotropic engineering slurry and filling treatment for use in underground void subsidence hazards. The optimal agent ratio for thixotropic cement slurry/mortar was obtained by indoor tests, where the rheological agent is 7.5% compared to the weight of cement, the water-solid ratio is in the range of 0.7~0.8, and the aeolian sand ratio can be 0~1.5 times that of cement. The rheological properties of slurry and mortar were tested using a Brookfield RST-SST rheometer. The results show that aeolian sand can be used as thixotropic cement mortar for a backfilling treatment for underground voids (mine goaf). The static yield stress increases non-linearly compared to existing thixotropic models. The stress decays sharply with shearing (the shear rate is more or less 10 s-1) and then the stress increases with the increase in shear rate (the shear rate is more than 10 s-1). The increase in the stress of the slurry is greater than in the mortar. A natural logarithmic function between yield stress and rest time (only 1 parameter), an exponential function with two parts for stress-shear rate (a rheology model, with only 3 parameters), and an exponential function for the accumulation law (only 2 parameters) were proposed in turn.

SLC26A4 mutation in Pendred syndrome with hypokalemia: A case report.

RATIONALE: Pendred syndrome is an autosomal recessive disorder characterized by sensorineural hearing loss, inner ear malformations, goiter, and abnormal organification of iodide. It is caused by mutations in SLC26A4 gene, which encodes pendrin (a transporter of chloride, bicarbonate, and iodide). Pendred syndrome is a common cause of syndromic deafness, but the metabolic abnormalities it causes are often overlooked. Here, we report the case of a patient diagnosed with Pendred syndrome with hypokalemia. PATIENT CONCERNS: A 53-year-old deaf-mute woman was hospitalized due to severe limb asthenia. The emergency examination showed that her blood potassium level was 1.8 mmol/L. DIAGNOSES: Through the genetic test, we found a mutation of SLC26A4 gene in NM_000441: c.2027T>A, p.L676Q, as well as the SLC26A4 exon 5-6 deletion. These genetic variations pointed to Pendred syndrome (an autosomal recessive disorder that mainly affects the inner ear, thyroid, and kidney) which is a common cause of syndromic deafness. INTERVENTIONS: The patient was treated with potassium supplements and screened for the cause of hypokalemia. OUTCOMES: The patient was discharged after her potassium levels rose to the normal range. LESSONS: Patients with Pendred syndrome may also have certain metabolic abnormalities; thus, more attention should be paid to them during clinical diagnosis.

Multifunctional MnCo@C yolk-shell nanozymes with smartphone platform for rapid colorimetric analysis of total antioxidant capacity and phenolic compounds.

Accurate on-site analysis of food quality, environmental pollutants, and disease biomarkers is of great significance for safeguarding public health. In this work, based on the novel nanozymes, MnCo oxides@carbon yolk-shell nanocages (MnCo@C NCs), a portable colorimetric sensor with smartphone platform has been developed for rapid, on-site and quantitative analysis of total antioxidant capacity (TAC) and phenolic compounds. The MnCo@C NCs are synthesized via one-step calcination of polydopamine-coated MnCo Prussian blue analogs (MnCo-PBA@PDA). The PDA-derived carbon shell is found to be able to protect the nanocages from collapsing, thus increasing their specific surface areas and porosity. Benefiting from the unique structure and multivalent MnCo bimetallic oxides, the MnCo@C NCs perform outstanding catalytic performance and multiple enzyme-mimicking activities including oxidase, laccase and catalase. Hence, a multifunctional application platform integrated smartphone has been constructed for rapid and sensitive colorimetric detection of three model analytes (i.e., ascorbic acid (AA), 2,4-dichlorophenol (2,4-DP), and epinephrine) with extremely low detection limits of 0.29 µM, 0.76 µM, and 0.70 µM, respectively. This sensor device is successfully applied in TAC analysis in vegetables, fruits, and beverages, as well as epinephrine determination in human serum samples. This work provides new insights into designing multifunctional nanozymes to advance the instant detection technology in the field of food supervision, environment monitoring, and human health.

The recognition of aristolochic acid I based on fluorescence quenching of bovine serum albumin-stabilized gold nanoclusters.

Aristolochic acid I (AAI) is one of the nephrotoxic derivatives present in genera Aristolochia and Asarum. Although some detection strategies for monitoring AAI have been reported, the application of these methods is limited because they involve tedious preparation and require professional operation. In this work, bovine serum albumin (BSA) has been introduced as a reducing agent and stabilizing agent to synthesize gold nanoclusters with strong red fluorescence for the rapid and effective detection of AAI. Under excitation at 328 nm, the fluorescence intensity at the maximum emission wavelength of the bovine serum albumin-stabilized gold nanoclusters (BSA-AuNCs) decreased with the addition of AAI, and the degree of quenching showed a linear relationship with the concentration of AAI from 0.1-12.8 µg mL-1. The obtained BSA-AuNCs were stable, and quenching in the presence of AAI could be achieved within 10 seconds. Here, we have focused on the application of these gold nanoclusters as an optical sensing material for AAI in rat urine samples, including a discussion on the detection mechanism. The detection result of the fluorescent probe was consistent with that of the HPLC method. In view of this reality, the reported protein-AuNCs sensing platform can serve as a convenient detection strategy in toxicological analyses.

Metabolic response of Lactobacillus acidophilus exposed to amoxicillin.

Drug-induced diarrhea is a common adverse drug reaction, especially the one caused by the widespread use of antibiotics. The reduction of probiotics is one reason for intestinal disorders induced by an oral antibiotic. However, the intrinsic mechanism of drug-induced diarrhea is still unknown. In this study, we used metabolomics methods to explore the effects of the classic oral antibiotic, amoxicillin, on the growth and metabolism of Lactobacillus acidophilus, while scanning electron microscopy (SEM) and 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays were employed to evaluate changes in cell activity and morphology. The results showed that cell viability gradually decreased, while the degree of cell wall rupture increased, with increasing amoxicillin concentrations. A non-targeted metabolomics analysis identified 13 potential biomarkers associated with 9 metabolic pathways. The data showed that arginine and proline metabolism, nicotinate and nicotinamide metabolism, pyrimidine metabolism, glycine, serine and threonine metabolism, beta-alanine metabolism, glycerolipid metabolism, tryptophan metabolism, steroid hormone biosynthesis, and histidine metabolism may be involved in the different effects exerted by amoxicillin on L. acidophilus. This study provides potential targets for screening probiotics regulators and lays a theoretical foundation for the elucidation of their mechanisms.

Predictive serum biomarkers of patients with cerebral infarction.

OBJECTIVES: Stroke is the third most common cause of death and also causes seizures and disability. Biomarkers are abnormal signal indicators at the biological level that are present before the organism is seriously affected and are more sensitive to early diagnosis than are traditional imaging methods. Early diagnosis of stroke can prevent the progression of the disease. However, there are currently no widely accepted biomarkers for stroke that have been applied clinically. METHODS: A serum metabonomics method based on ultra-high-performance liquid chromatography-quadrupole-time of flight tandem mass spectrometry (UPLC-Q-TOF/MS) was used to identify potential biomarkers and metabolic pathways of cerebral infarction. The receiver-operating characteristic (ROC) curve was used to verify the diagnostic and classification abilities of the biomarkers, and a support vector machine (SVM) model was developed for the prediction of cerebral infarction. RESULTS: Principal component analysis revealed a clear separation between the normal and cerebral infarction groups. A total of 13 potential serum biomarkers were identified, which were mainly involved in linoleic acid metabolism; phenylalanine, tyrosine, and tryptophan biosynthesis; tyrosine metabolism; arachidonic acid metabolism; and fatty acid biosynthesis. The ROC curve analysis showed that the potential biomarkers had high specificity and sensitivity for the diagnosis of cerebral infarction. The SVM model had good diagnostic ability and could accurately distinguish the control group from the cerebral infarction group. DISCUSSION: The metabonomics approach may be a useful bioanalytical method for understanding the pathophysiology of cerebral infarction and may provide an experimental basis for the development of clinical biomarkers for stroke.