Upstream and downstream regulators of Klotho expression in chronic kidney disease.

Klotho is a critical protein that protects the kidney. Klotho is severely downregulated in chronic kidney disease (CKD), and its deficiency is implicated in the pathogenesis and progression of CKD. Conversely, an increase in Klotho levels results in improved kidney function and delays CKD progression, supporting the notion that modulating Klotho levels could represent a possible therapeutic strategy for CKD treatment. Nevertheless, the regulatory mechanisms responsible for the loss of Klotho remain elusive. Previous studies have demonstrated that oxidative stress, inflammation, and epigenetic modifications can modulate Klotho levels. These mechanisms result in a decrease in Klotho mRNA transcript levels and reduced translation, thus can be grouped together as upstream regulatory mechanisms. However, therapeutic strategies that aim to rescue Klotho levels by targeting these upstream mechanisms do not always result in increased Klotho, indicating the involvement of other regulatory mechanisms. Emerging evidence has shown that endoplasmic reticulum (ER) stress, the unfolded protein response, and ER-associated degradation also affect the modification, translocation, and degradation of Klotho, and thus are proposed to be downstream regulatory mechanisms. Here, we discuss the current understanding of upstream and downstream regulatory mechanisms of Klotho and examine potential therapeutic strategies to upregulate Klotho expression for CKD treatment.

Comparability of sample results and commutability of reference materials among different measurement procedures for protein C activity assays.

BACKGROUND AND AIMS: Several types of measurement procedures (MPs) for protein C activity assays are currently available. Clinical sample (CS) results among different MPs should be comparable. The commutability of reference materials (RMs) is an essential requirement to achieve comparability of CS results. MATERIALS AND METHODS: Considering the total error calculated using reliable biological variation (BV) data and external quality assessment (EQA) criteria, we chose the allowable limits of comparability and criterion of commutability. According to Clinical and Laboratory Standardization Institute EP9 and our previous studies, 92 CSs were used to evaluate the comparability among the three MPs (Sysmex CS-5100, IL ACL TOP 700, and STA-R Evolution). The difference in bias method recommended by International Federation of Clinical Chemistry and Laboratory Medicine was used to assess the commutability of six RMs, including World Health Organization (WHO) IS 02/342. RESULTS: The compliance rates of CSs were 94.6-100% with the corresponding calibration mode. WHO IS, HemosIL calibration plasma, and candidate RMs, PC20201 and PC20202, were commutable between each pair of the three MPs. CONCLUSION: It is feasible to set the allowable limits of comparability and the criterion of commutability based on the BV and EQA criteria.

Comparison among different measurement systems for fibrinogen using fresh samples and frozen samples.

BACKGROUND: Many laboratories in China have several types of coagulation analyzers. Differences in fibrinogen results among different systems may cause inappropriate medical decisions. Our aim was to set the comparability evaluation criteria and evaluate comparability of different fibrinogen measurement systems using fresh and frozen samples. METHODS: Biological variation (BV) publications on fibrinogen were reviewed. Total error based on reliable BV data and external quality assessment (EQA) criteria were combined to set allowable limit. The compliance rate of samples for the limit should achieve at least 80% if the results obtained from different systems were comparable. Fifty-seven samples before and after freeze-thaw were measured by three measurement systems and the percentage of compliant samples was calculated. RESULTS: The allowable limit was 11.3%. The compliance rates of fresh samples were 78.2-84.2%, and the rates of frozen samples were 54.5-93.0%. The comparability results were different using two kinds of samples. CONCLUSIONS: It is feasible to set allowable limits of comparability based on BV and state of the art; and fresh samples are recommended for evaluating systems comparability. The results of comparability are related to samples' concentrations distribution, which should range over the concentration ranges in routine laboratory tests.

A Supervised Speech Enhancement Method for Smartphone-Based Binaural Hearing Aids.

It is essential but quite challenging to alleviate speech information loss and distortion while developing the speech processing algorithms in hearing aids. Recently, many speech enhancement methods based on deep learning are proven effective. However, most of the algorithms fail to achieve real-time processing, which is significant for hearing aids, especially for a smartphone-centered binaural hearing aid system. A supervised speech enhancement method based on an RNN structure is proposed to address the real-time problem. The problem is explored as a resource-constrained speech intelligibility improvement problem with the target of improving speech intelligibility at low SNR situations. The objective experimental result using the standard evaluation metrics has verified the superiority of the proposed method. The trial use by a small number of volunteers also indicates that the user experience has been improved with the proposed method.