Association of systemic inflammation response index with latent tuberculosis infection and all-cause mortality: a cohort study from NHANES 2011-2012.

Background: The Systemic Inflammatory Response Index (SIRI) is a promising inflammatory marker; however, the relationship between SIRI and latent tuberculosis infection (LTBI), as well as its association with mortality rates, remains unclear. The present study aimed to explore the associations of the SIRI with LTBI and all-cause mortality.

Methods: We conducted a prospective cohort study using data from National Health and Nutrition Examination Survey (NHANES) cycles from 2011 to 2012.

Performance Validation of the NeoBase 2 Non-Derivatized MSMS Assay Kit and Cutoff Values Establishment of Term and Preterm Neonates.

Objective: NeoBase 2 Non-derivatized MSMS assay kit (NeoBase 2 kit) was used for newborn screening, the performance of the NeoBase 2 kit should be validated before its implementation in clinical diagnostic laboratories.

Methods: Leftover dried blood spot samples, quality control materials in the NeoBase 2 kit, and proficiency testing materials received from the NSQAP were used. Precision, accuracy, LOD, LLOQ, recovery, and stability were carried out to verify the performance of the Waters ACQUITY TQD MS/MS system with the NeoBase 2 kit for newborn screening.

An open-label randomized controlled trial of leflunomide in patients with acute SARS-CoV-2 omicron variant infection.

Objective: To evaluate the efficacy and safety of leflunomide for the treatment of acute, symptomatic COVID-19.

Methods: A single-center, open-label, randomized controlled trial was performed during an outbreak of SARS-CoV-2 Omicron variant in December 2022. Symptomatic patients within 5 days of COVID-19 onset were randomly allocated to receive 5 days of either symptomatic treatment with leflunomide or symptomatic treatment alone.

Tempol modulates lncRNA-miRNA-mRNA ceRNA networks in ovaries of DHEA induced PCOS rats.

Polycystic ovary syndrome (PCOS) is one of the most common endocrine and metabolic disorders in reproductive age women. Our previous results demonstrated that tempol was able to ameliorate PCOS phenotype in rats. However, the exact pathophysiological effect of tempol on PCOS remains largely unknown.

Mitochondrial quality control links two seemingly unrelated neurodegenerative diseases.

Despite certain overlapping clinical presentations, the two human neurodegenerative diseases pantothenate kinase-associated neurodegeneration (PKAN) and Parkinson disease (PD) have distinct genetic etiologies. During our work using Drosophila to study PKAN and PINK1-related PD, we found some common mitochondrial abnormalities in these two disease models, suggesting a potential link in pathogenesis between them. When we delve into their underlying mechanisms, mitochondrial quality control (MQC) stands at the crossroads.

Pantothenate kinase 2 interacts with PINK1 to regulate mitochondrial quality control via acetyl-CoA metabolism.

Human neurodegenerative disorders often exhibit similar pathologies, suggesting a shared aetiology. Key pathological features of Parkinson's disease (PD) are also observed in other neurodegenerative diseases. Pantothenate Kinase-Associated Neurodegeneration (PKAN) is caused by mutations in the human PANK2 gene, which catalyzes the initial step of de novo CoA synthesis.

Benchmark Examination of Blood Amino Acids Patterns in Phenylketonuria Neonates and Young Children on Phenylalanine-Restricted Dietary Treatment.

Phenylalanine-restricted diets have been the basis of therapy for phenylketonuria; however, little is known how this treatment effects homeostasis of other amino acids. This study aimed to assess blood amino acid alterations in phenylketonuric neonates before and after treatment to identify any residual amino acid alterations with phenylalanine restriction in these treated children. Concentrations of 11 amino acids were measured using liquid chromatography-tandem mass spectrometry performed on dried blood spots.

Treatment of Coronavirus Disease 2019 Patients With Prolonged Postsymptomatic Viral Shedding With Leflunomide: A Single-center Randomized Controlled Clinical Trial.

Background: We aimed to evaluate the efficacy and safety of leflunomide, an approved dihydroorotate dehydrogenase inhibitor, to treat coronavirus disease 2019 (COVID-19) patients with prolonged postsymptomatic viral shedding.

Methods: We conducted a prospective, randomized controlled, open-label trial involving hospitalized adult COVID-19 patients with prolonged polymerase chain reaction (PCR) positivity. Patients were randomly assigned to receive either leflunomide (50 mg every 12 hours, 3 consecutive times, orally; then 20 mg once daily for 8 days), in addition to nebulized interferon alpha 2a (IFN-α-2a, 3 million IU each time, twice daily for 10 days), or nebulized IFN-α-2a alone for 10 days.

Elevating bioavailable iron levels in mitochondria suppresses the defective phenotypes caused by PINK1 loss-of-function in Drosophila melanogaster.

Parkinson's disease (PD) is the second most common progressive neurodegenerative disease, which is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Iron deposit was found in the SNpc of PD patients and animal models, however, the mechanisms involved in disturbed iron metabolism remain unknown. Identifying the relationship between iron metabolism and PD is important for finding new therapeutic strategies.

Inborn errors of metabolism detectable by tandem mass spectrometry in Beijing.

Background Individual inborn errors of metabolism (IEMs) are rare disorders. Expanded newborn screening for IEMs by tandem mass spectrometry (TMS) is an efficient approach for early diagnosis. Here we provide the newborn screening program for the application of this approach (between July 2014 and March 2019) to the identification of newborns in Beijing at risk of developing a potentially fatal disease.

Clinical, biochemical and molecular spectrum of mild 6-pyruvoyl-tetrahydropterin synthase deficiency and a case report.

6-Pyruvoyl-tetrahydropterin synthase (PTS) is the key enzyme in BH4 synthesis. PTS deficiency is classified as severe type and mild type, and the prognosis and treatment differ for these types. Distinguishing between two types in the early stage is difficult.

Drosophila ZIP13 is posttranslationally regulated by iron-mediated stabilization.

Drosophila ZIP13 (dZIP13, CG7816/ZIP99C) belongs to the SLC39A family and is connected to iron homeostasis in the fruit fly. In this study, we show that dZIP13 level is strongly regulated by iron. In addition to a mild response to iron at the mRNA level, dZIP13 is strongly regulated at the protein level.

Insulin signaling in mediates Aβ toxicity.

Alzheimer's disease (AD) and diabetes are clinically positively correlated. However, the connection between them is not clarified. Here, using as a model system, we show that reducing insulin signaling can effectively suppress the toxicity from Aβ (Amyloid beta 42) expression.

RVG29-modified docetaxel-loaded nanoparticles for brain-targeted glioma therapy.

Gliomas are the most common malignant brain tumor, but treatment is limited by the blood-brain barrier (BBB), especially for chemotherapeutic drugs. Although some chemotherapy drugs can pass through the BBB, many of these agents are toxic to normal brain tissue. To maximize therapeutic effects, chemotherapeutic drugs must accumulate at the glioma site.

Metal-metal interaction mediates the iron induction of Drosophila MtnB.

Metallothionein (MT) protein families are a class of small and universal proteins rich in cysteine residues. They are synthesized in response to heavy metal stresses to sequester the toxic ions by metal-thiolate bridges. Five MT family members, namely MtnA, MtnB, MtnC, MtnD and MtnE, have been discovered and identified in Drosophila.

The metal transporter ZIP13 supplies iron into the secretory pathway in Drosophila melanogaster.

The intracellular iron transfer process is not well understood, and the identity of the iron transporter responsible for iron delivery to the secretory compartments remains elusive. In this study, we show Drosophila ZIP13 (Slc39a13), a presumed zinc importer, fulfills the iron effluxing role. Interfering with dZIP13 expression causes iron-rescuable iron absorption defect, simultaneous iron increase in the cytosol and decrease in the secretory compartments, failure of ferritin iron loading, and abnormal collagen secretion.

Highly efficient hierarchical micelles integrating photothermal therapy and singlet oxygen-synergized chemotherapy for cancer eradication.

It is highly desirable to develop theranostic nanoparticles for achieving cancer imaging with enhanced contrast and simultaneously multimodal synergistic therapy. Herein, we report a theranostic micelle system hierarchically assembling cyanine dye (indocyanine green) and chemotherapeutic compound (doxorubicin) (I/D-Micelles) as a novel theranostic platform with high drug loading, good stability and enhanced cellular uptake via clathrin-mediated endocytosis. I/D-Micelles exhibit the multiple functionalities including near-infrared fluorescence (NIRF), hyperthermia and intracellular singlet oxygen from indocyanine green, and simultaneous cytotoxicity from doxorubicin.

Micelles assembled with carbocyanine dyes for theranostic near-infrared fluorescent cancer imaging and photothermal therapy.

It is an emerging focus to explore a theranostic nanocarrier for simultaneous cancer imaging and therapy. Herein, we demonstrate a theranostic micelle system for cancer near infrared fluorescent (NIRF) imaging with enhanced signal to noise ratio and superior photothermal therapy. The copolymers consisting of monomethoxy poly(ethylene glycol) and alkylamine-grafted poly(L-aspartic acid) are assembled with carbocyanine dyes into theranostic micelles, which exhibit small size, high loading capacity, good stability, sustained release behavior, and enhanced cellular uptake.

Diarylquinoline compounds induce autophagy-associated cell death by inhibiting the Akt pathway and increasing reactive oxygen species in human nasopharyngeal carcinoma cells.

Diarylquinoline compounds are newly synthesized derivatives of the new anti-tuberculosis drug, TMC207. In this study, nine diarylquinoline compounds were screened for cytotoxic activity against human tumor cells, and their mechanisms of action were investigated. Among the nine compounds, STM-57 [N-((6-bromo-2-methoxyquinolin-3-yl)(phenyl)methl)-N-(3,4-dichlorophenyl)-3-(4 -methylpiperazin-1-yl)propanamide] showed potent cytotoxic activity.

[A novel COL4A5 splicing mutation causing Alport syndrome in a Chinese family].

Objective: To identify the pathogenic mutation in a Chinese family with Alport syndrome.

Methods: Blood samples were collected from the members of the family. Direct DNA sequence analysis of the entire coding region and exon-intron boundaries of the COL4A5 gene was performed, and restriction fragment length polymorphism (RFLP) analysis was used to confirm the sequencing results and to test the mutation in all the family members and 200 controls.