Self-improving dystrophic epidermolysis bullosa with a novel heterozygous missense variant in the COL7A1 gene in a Taiwanese family.

Self-improving dystrophic epidermolysis bullosa (DEB) is a genodermatosis that is inherited autosomal dominantly or recessively, and its clinical symptoms may improve or subside spontaneously. Herein, we report a case of self-improving DEB with COL7A1 p.Gly2025Asp variant. The diagnosis was made through histopathological, electron microscopic examination, and genetic testing. The same variant is also noted on his father, who presents with dystrophic toenails without any blisters. This study highlights that idiopathic nail dystrophy could be linked to congenital or hereditary disease. Furthermore, we conducted a review of the literature on the characteristics of reported cases of self-improving DEB with a personal or family history of nail dystrophy. The results supported our findings that nail dystrophy may be the sole manifestation in some family members. We suggest that individuals suffering from idiopathic nail dystrophy may seek genetic counselling when planning pregnancy to early evaluate the potential risk of hereditary diseases.

[A consensus on prenatal diagnosis and genetic counseling for chromosomal mosaicism].

With the extensive application of highly sensitive genetic techniques in the field of prenatal diagnosis, prenatal chromosomal mosaicisms including true fetal mosaicisms and confined placental mosaicisms are frequently identified in clinical settings, and the diagnostic criteria and principle of genetic counseling and clinical management for such cases may vary significantly among healthcare centers across the country. This not only has brought challenges to laboratory technician, genetic counselor and fetal medicine doctor, but can also cause confusion and anxiety of the pregnant woman and their family members. In this regard, we have formulated a consensus over the prenatal diagnosis and genetic counseling for chromosomal mosaicisms with the aim to promote more accurate and rational evaluation for fetal chromosomal mosaicisms in prenatal clinics.

The Setup and Application of Reference Material in Sequencing-Based Noninvasive Prenatal Testing.

INTRODUCTION: The sequencing-based noninvasive prenatal testing (NIPT) has been successfully integrated into clinical practice and facilitated the early detection of fetal chromosomal anomalies. However, a comprehensive reference material to evaluate and quality control NIPT services from different NIPT providers remains unavailable. METHODS: In this study, we established a set of NIPT reference material consisting of 192 simulated samples. Most of the potential factors influencing the accuracy of NIPT, such as fetal fraction, mosaicism, and interfering substances, were included in the reference material. We compared the performance of chromosomal abnormalities detection on 3 widely used sequencers (NextSeq 500, BGISEQ-500, and Ion Proton) based on the reference material. RESULTS: All 3 sequencers provided highly accurate and reliable results to samples with ≥3.5% fetal fractions and high percentage of mosaicism. CONCLUSIONS: The established reference material can serve as a universal standard quality control for the current and new-coming NIPT providers based on various sequencers.

[Consensus on technological standards for non-invasive prenatal screening of pathogenic copy number variations by high-throughput sequencing of maternal plasma cell-free DNA].

Genomic disorders caused by pathogenic copy number variation (pCNV) have proven to underlie a significant proportion of birth defects. With technological advance, improvement of bioinformatics analysis procedure, and accumulation of clinical data, non-invasive prenatal screening of pCNV (NIPS-pCNV) by high-throughput sequencing of maternal plasma cell-free DNA has been put to use in clinical settings. Specialized standards for clinical application of NIPS-pCNV are required. Based on the discussion, 10 pCNV-associated diseases with well-defined conditions and 5 common chromosomal aneuploidy syndromes are recommended as the target of screening in this consensus. Meanwhile, a standardized procedure for NIPS-pCNV is also provided, which may facilitate propagation of this technique in clinical settings.

Noninvasive prenatal detection of hemoglobin Bart hydrops fetalis via maternal plasma dispensed with parental haplotyping using the semiconductor sequencing platform.

BACKGROUND: Thalassemia is one of the most common monogenetic diseases in the south of China and Southeast Asia. Hemoglobin Bart's hydrops fetalis syndrome was caused by a homozygous Southeast Asian deletion (-/-) in the HBA gene. Few studies have proved the potential of screen for Bart's hydrops fetalis using fetal cell-free DNA. However, the number of cases is still relatively small. Clinical trials of large samples would be needed. OBJECTIVE: In this study, we aimed to develop a noninvasive method of target-captured sequencing and genotyping by the Bayesian method using cell-free fetal DNA to identify the fetal genotype in pregnant women who are at risk of having hemoglobin Bart hydrops fetalis in a large-scale study. STUDY DESIGN: In total, 192,173 couples from 30 hospitals were enrolled in our study and 878 couples were recruited, among whom both the pregnant women and their husbands were detected to be carriers of Southeast Asian type (-/αα) of α-thalassemia. Prenatal diagnosis was performed by chorionic villus sampling, amniocentesis, or cordocentesis using gap-polymerase chain reaction considered as the golden standard. RESULTS: As a result, we found that the sensitivity and specificity of our noninvasive method were 98.81% and 94.72%, respectively, in the training set as well as 100% and 99.31%, respectively, in the testing set. Moreover, our method could identify all of 885 maternal samples with the Southeast Asian carrier and 36 trisomy samples with 100% of sensitivity in T13, T18, and T21 and 99.89% (1 of 917) and 99.88% (1 of 888) of specificity in T18 and T21, respectively. CONCLUSION: Our method opens the possibility of early screening for maternal genotyping of α-thalassemia, fetal aneuploidies in chromosomes 13/18/21, and hemoglobin Bart hydrops fetalis detection in 1 tube of maternal plasma.

Evaluation of Radioiodinated Fluoronicotinamide/Fluoropicolinamide-Benzamide Derivatives as Theranostic Agents for Melanoma.

Malignant melanoma is the most harmful type of skin cancer and its incidence has increased in this past decade. Early diagnosis and treatment are urgently desired. In this study, we conjugated picolinamide/nicotinamide with the pharmacophore of 131I-MIP-1145 to develop 131I-iodofluoropicolinamide benzamide (131I-IFPABZA) and 131I-iodofluoronicotiamide benzamide (131I-IFNABZA) with acceptable radiochemical yield (40 ± 5%) and high radiochemical purity (>98%). We also presented their biological characteristics in melanoma-bearing mouse models. 131I-IFPABZA (Log P = 2.01) was more lipophilic than 131I-IFNABZA (Log P = 1.49). B16F10-bearing mice injected with 131I-IFNABZA exhibited higher tumor-to-muscle ratio (T/M) than those administered with 131I-IFPABZA in planar γ-imaging and biodistribution studies. However, the imaging of 131I-IFNABZA- and 131I-IFPABZA-injected mice only showed marginal tumor uptake in A375 amelanotic melanoma-bearing mice throughout the experiment period, indicating the high binding affinity of these two radiotracers to melanin. Comparing the radiation-absorbed dose of 131I-IFNABZA with the melanin-targeted agents reported in the literature, 131I-IFNABZA exerts lower doses to normal tissues on the basis of similar tumor dose. Based on the in vitro and in vivo studies, we clearly demonstrated the potential of using 131I-IFNABZA as a theranostic agent against melanoma.

An enrichment method to increase cell-free fetal DNA fraction and significantly reduce false negatives and test failures for non-invasive prenatal screening: a feasibility study.

BACKGROUND: Noninvasive prenatal screening (NIPS) based on cell-free fetal DNA (cffDNA) has rapidly been applied into clinic. However, the reliability of this method largely depends on the concentration of cffDNA in the maternal plasma. The chance of test failure results or false negative results would increase when cffDNA fraction is low. In this study, we set out to develop a method to enrich the cffDNA for NIPS based on the size difference between cell-free DNA (cfDNA) of fetal origin and maternal origin, and to evaluate whether the new NIPS method can improve the test quality. METHODS: We utilized 10,000 previous NIPS data to optimize a size-selection strategy for enrichment. Then, we retrospectively performed our new NIPS method with cffDNA enrichment on the 1415 NIPS samples, including 1404 routine cases and 11 false negative cases, and compared the results to the original NIPS results. RESULTS: The 10,000 NIPS data revealed the fetal fraction in short cfDNA fragments (< 160 bp) is significantly higher. By using our new NIPS strategy on the 1404 routine cases, the fetal fraction increased from 11.3 ± 4.2 to 22.6 ± 6.6%, and the new method performed a significant decrease of test-failure rate (0.1% vs 0.7%, P < 0.01). Moreover, in 45.5% (5/11) of the false negative cases, fetal trisomies were successfully detected by our new NIPS method. CONCLUSIONS: We developed an effective method to enrich cffDNA for NIPS, which shows an increased success rate and a reduced chance of false negative comparing to the ordinary NIPS method.

Development of a novel radioligand for imaging 18-kD translocator protein (TSPO) in a rat model of Parkinson's disease.

PURPOSE: The inflammation reaction in the brain may stimulate damage repair or possibly lead to secondary brain injury. It is often associated with activated microglia, which would overexpress 18-kDa translocator protein (TSPO). In this study, we successfully developed a new TSPO radioligand, [18F]-2-(4-fluoro-2-(p-tolyloxy)phenyl)-1,2-dihydroisoquinolin-3(4H)-one ([18F]FTPQ), and evaluate its potential to noninvasively detect brain changes in a rat model of Parkinson's disease (PD). PROCEDURES: The precursor (8) for [18F]FTPQ preparation was synthesized via six steps. Radiofluorination was carried out in the presence of a copper catalyst, and the crude product was purified by high-performance liquid chromatography (HPLC) to give the desired [18F]FTPQ. The rat model of PD was established by the injection of 6-OHDA into the right hemisphere of male 8-week-old Sprague-Dawley rats. MicroPET/CT imaging and immunohistochemistry (IHC) were performed to characterize the biological properties of [18F]FTPQ. RESULTS: The overall chemical yield for the precursor (8) was around 14% after multi-step synthesis. The radiofluorination efficiency of [18F]FTPQ was 60 ± 5%. After HPLC purification, the radiochemical purity was higher than 98%. The overall radiochemical yield was approximately 19%. The microPET/CT images demonstrated apparent striatum accumulation in the brains of PD rats at the first 30 min after intravenous injection of [18F]FTPQ. Besides, longitudinal imaging found the uptake of [18F]FTPQ in the brain may reflect the severity of PD. The radioactivity accumulated in the ipsilateral hemisphere of PD rats at 1, 2, and 3 weeks after 6-OHDA administration was 1.84 ± 0.26, 3.43 ± 0.45, and 5.58 ± 0.72%ID/mL, respectively. IHC revealed that an accumulation of microglia/macrophages and astrocytes in the 6-OHDA-injected hemisphere. CONCLUSIONS: In this study, we have successfully synthesized [18F]FTPQ with acceptable radiochemical yield and demonstrated the feasibility of [18F]FTPQ as a TSPO radioligand for the noninvasive monitoring the disease progression of PD.

A Policy for Optimizing Sub-Band Selection Sequences in Wideband Spectrum Sensing.

With the development of wireless communication technology, cognitive radio needs to solve the spectrum sensing problem of wideband wireless signals. Due to performance limitation of electronic components, it is difficult to complete spectrum sensing of wideband wireless signals at once. Therefore, it is required that the wideband wireless signal has to be split into a set of sub-bands before the further signal processing. However, the sequence of sub-band perception has become one of the important factors, which deeply-impact wideband spectrum sensing performance. In this paper, we develop a novel approach for sub-band selection through the non-stationary multi-arm bandit (NS-MAB) model. This approach is based on a well-known order optimal policy for NS-MAB mode called discounted upper confidence bound (D-UCB) policy. In this paper, according to different application requirements, various discount functions and exploration bonuses of D-UCB are designed, which are taken as the parameters of the policy proposed in this paper. Our simulation result demonstrates that the proposed policy can provide lower cumulative regret than other existing state-of-the-art policies for sub-band selection of wideband spectrum sensing.

Optimized Non-Cooperative Spectrum Sensing Algorithm in Cognitive Wireless Sensor Networks.

The cognitive wireless sensor network (CWSN) is an important development direction of wireless sensor networks (WSNs), and spectrum sensing technology is an essential prerequisite for CWSN to achieve spectrum sharing. However, the existing non-cooperative narrowband spectrum sensing technology has difficulty meeting the application requirements of CWSN at present. In this paper, we present a non-cooperative spectrum sensing algorithm for CWSN, which combines the multi-resolution technique, phase space reconstruction method, and singular spectrum entropy method to sense the spectrum of narrowband wireless signals. Simulation results validate that this algorithm can greatly improve the detection probability at a low signal-to-noise ratio (SNR) (from -19dB to -12dB), and the detector can quickly achieve the best detection performance as the SNR increases. This algorithm could promote the development of CWSN and the application of WSNs.

Noninvasive detection of fetal subchromosomal abnormalities by semiconductor sequencing of maternal plasma DNA.

Noninvasive prenatal testing (NIPT) using sequencing of fetal cell-free DNA from maternal plasma has enabled accurate prenatal diagnosis of aneuploidy and become increasingly accepted in clinical practice. We investigated whether NIPT using semiconductor sequencing platform (SSP) could reliably detect subchromosomal deletions/duplications in women carrying high-risk fetuses. We first showed that increasing concentration of abnormal DNA and sequencing depth improved detection. Subsequently, we analyzed plasma from 1,456 pregnant women to develop a method for estimating fetal DNA concentration based on the size distribution of DNA fragments. Finally, we collected plasma from 1,476 pregnant women with fetal structural abnormalities detected on ultrasound who also underwent an invasive diagnostic procedure. We used SSP of maternal plasma DNA to detect subchromosomal abnormalities and validated our results with array comparative genomic hybridization (aCGH). With 3.5 million reads, SSP detected 56 of 78 (71.8%) subchromosomal abnormalities detected by aCGH. With increased sequencing depth up to 10 million reads and restriction of the size of abnormalities to more than 1 Mb, sensitivity improved to 69 of 73 (94.5%). Of 55 false-positive samples, 35 were caused by deletions/duplications present in maternal DNA, indicating the necessity of a validation test to exclude maternal karyotype abnormalities. This study shows that detection of fetal subchromosomal abnormalities is a viable extension of NIPT based on SSP. Although we focused on the application of cell-free DNA sequencing for NIPT, we believe that this method has broader applications for genetic diagnosis, such as analysis of circulating tumor DNA for detection of cancer.

Noninvasive prenatal diagnosis of common aneuploidies by semiconductor sequencing.

Massively parallel sequencing (MPS) of cell-free fetal DNA from maternal plasma has revolutionized our ability to perform noninvasive prenatal diagnosis. This approach avoids the risk of fetal loss associated with more invasive diagnostic procedures. The present study developed an effective method for noninvasive prenatal diagnosis of common chromosomal aneuploidies using a benchtop semiconductor sequencing platform (SSP), which relies on the MPS platform but offers advantages over existing noninvasive screening techniques. A total of 2,275 pregnant subjects was included in the study; of these, 515 subjects who had full karyotyping results were used in a retrospective analysis, and 1,760 subjects without karyotyping were analyzed in a prospective study. In the retrospective study, all 55 fetal trisomy 21 cases were identified using the SSP with a sensitivity and specificity of 99.94% and 99.46%, respectively. The SSP also detected 16 trisomy 18 cases with 100% sensitivity and 99.24% specificity and 3 trisomy 13 cases with 100% sensitivity and 100% specificity. Furthermore, 15 fetuses with sex chromosome aneuploidies (10 45,X, 2 47,XYY, 2 47,XXX, and 1 47,XXY) were detected. In the prospective study, nine fetuses with trisomy 21, three with trisomy 18, three with trisomy 13, and one with 45,X were detected. To our knowledge, this is the first large-scale clinical study to systematically identify chromosomal aneuploidies based on cell-free fetal DNA using the SSP and provides an effective strategy for large-scale noninvasive screening for chromosomal aneuploidies in a clinical setting.

Downregulation of glutathione S-transferase M1 protein in N-butyl-N-(4-hydroxybutyl)nitrosamine-induced mouse bladder carcinogenesis.

Bladder cancer is highly recurrent following specific transurethral resection and intravesical chemotherapy, which has prompted continuing efforts to develop novel therapeutic agents and early-stage diagnostic tools. Specific changes in protein expression can provide a diagnostic marker. In our present study, we investigated changes in protein expression during urothelial carcinogenesis. The carcinogen BBN was used to induce mouse bladder tumor formation. Mouse bladder mucosa proteins were collected and analyzed by 2D electrophoresis from 6 to 20 weeks after commencing continuous BBN treatment. By histological examination, the connective layer of the submucosa showed gradual thickening and the number of submucosal capillaries gradually increased after BBN treatment. At 12-weeks after the start of BBN treatment, the urothelia became moderately dysplastic and tumors arose after 20-weeks of treatment. These induced bladder lesions included carcinoma in situ and connective tissue invasive cancer. In protein 2D analysis, the sequentially downregulated proteins from 6 to 20 weeks included GSTM1, L-lactate dehydrogenase B chain, keratin 8, keratin 18 and major urinary proteins 2 and 11/8. In contrast, the sequentially upregulated proteins identified were GSTO1, keratin 15 and myosin light polypeptide 6. Western blotting confirmed that GSTM1 and NQO-1 were decreased, while GSTO1 and Sp1 were increased, after BBN treatment. In human bladder cancer cells, 5-aza-2'-deoxycytidine increased the GSTM1 mRNA and protein expression. These data suggest that the downregulation of GSTM1 in the urothelia is a biomarker of bladder carcinogenesis and that this may be mediated by DNA CpG methylation.

Chaperonin containing TCP1 subunit 6A may activate Notch and Wnt pathways to facilitate the malignant behaviors and cancer stemness in oral squamous cell carcinoma.

Chaperonin containing TCP1 subunit 6A (CCT6A) was recently discovered to be involved in cancer pathogenesis and stemness; however, its role in oral squamous cell carcinoma (OSCC) has not been reported. The current study aimed to investigate the impact of CCT6A on OSCC cell malignant behaviors and stemness and to explore its potentially interreacted pathways. SCC-15 and HSC-3 cells were transfected with the plasmid loading control overexpression, CCT6A overexpression, control knockout, or CCT6A knockout. Wnt4 overexpression or Notch1 overexpression plasmids were transfected into CCT6A-knockout SCC-15 cells. Cell proliferation, apoptosis, invasion, stemness, Notch, and Wnt pathways were detected in both cell lines, whereas RNA sequencing was only performed in SCC-15 cells. CCT6A was upregulated in five OSCC cell lines, including SCC-15, HSC-3, SAT, SCC-9, and KON, compared to that in the control cell line. In SCC-15 and HSC-3 cells, CCT6A overexpression increased cell proliferation, invasion, sphere formation, CD133, and Sox2 expression, but decreased cell apoptosis; on the contrary, CCT6A knockout exhibited an opposite effect on the above indexes. RNA-sequencing data revealed that the Wnt and Notch pathways were involved in the CCT6A'effect on SCC-15 cell functions. CCT6A positively regulates the Wnt and Notch pathways in SCC-15 and HSC-3 cells. Importantly, it was shown that activation of the Wnt or Notch pathways attenuated the effect of CCT6A knockout on SCC-15 cell survival, invasion, and stemness. CCT6A may promote OSCC malignant behavior and stemness by activating the Wnt and Notch pathways.

Serum cell division control 42 reflects treatment response and survival profiles in recurrent or metastatic oral squamous cell carcinoma patients who receive programmed death-1 inhibitors.

OBJECTIVES: Cell division control 42 (CDC42) facilitates tumor growth, migration, and immune escape to accelerate the pathogenesis and progression of oral squamous cell carcinoma (OSCC). This study intended to explore the optimal cut-value of serum CDC42 for predicting treatment response to programmed death-1 (PD-1) inhibitors and survival in recurrent or metastatic (R/M) OSCC patients. METHODS: CDC42 was detected from serum by enzyme-linked immunosorbent assay in 45 R/M OSCC patients before initiating PD-1 inhibitors with or without chemotherapy. Different cutoff values (500, 600, 700, and 800 pg/mL) of CDC42 were selected for further analyses. RESULTS: The median (interquartile range) value of CDC42 was 604.0 (477.5-867.5) pg/mL in R/M OSCC patients. Generally, objective response rate (ORR) and disease control rate (DCR) were 37.8 % and 62.2 %. Additionally, ORR (P = 0.030) and DCR (P = 0.004) were decreased in patients with CDC42 ≥ 700 pg/mL versus those with CDC42 < 700 pg/mL; meanwhile, DCR was also reduced in patients with CDC42 ≥ 800 pg/mL versus those with CDC42 < 800 pg/mL (P = 0.014). Interestingly, CDC42 ≥ 600 (P = 0.023), 700 (P = 0.007), and 800 (P = 0.039) pg/mL were related to shorter progression-free survival (PFS). While only CDC42 ≥ 700 (P = 0.004) and 800 (P = 0.046) pg/mL were correlated with worse overall survival (OS). After adjustment, only CDC42 ≥ 700 pg/mL (yes vs. no) independently estimated poor PFS (hazard ratio (HR) = 2.637, P = 0.005) and OS (HR = 5.824, P < 0.001). CONCLUSION: CDC42 ≥ 700 pg/mL exerts the optimal prognostic ability to reflect poor treatment response and survival profiles in R/M OSCC patients who receive PD-1 inhibitors.

Assessing leaf physiological traits in response to flooding among dominant riparian herbs along the Three Gorges Dam in China.

Dams worldwide have significantly altered the composition of riparian forests. However, research on the functional traits of dominant herbs experiencing flooding stress due to dam impoundment remains limited. Given the high plasticity of leaf traits and their susceptibility to environmental influences, this study focuses on riparian herbs along the Three Gorges Hydro-Fluctuation Zone (TGHFZ). Specifically, it investigates how six leaf physiological traits of leading herbs-carbon, nitrogen, phosphorus, and their stoichiometric ratios-adapt to periodic flooding in the TGHFZ using cluster analysis, one-way analysis of variance (ANOVA), multiple comparisons, Pearson correlation analysis, and principal component analysis (PCA). We categorized 25 dominant herb species into three plant functional types (PFTs), noting that species from the same family tended to fall into the same PFT. Notably, leaf carbon content (LCC) exhibited no significant differences across various PFTs or altitudes. Within riparian forests, different PFTs employ distinct adaptation strategies: PFT-I herbs invest in structural components to enhance stress resistance; PFT-II, mostly comprising gramineous plants, responds to prolonged flooding by rapid growth above the water; and PFT-III, encompassing nearly all Compositae and annual plants, responds to prolonged flooding with vigorous rhizome growth and seed production. Soil water content (SWC) emerges as the primary environmental factor influencing dominant herb growth in the TGHFZ. By studying the response of leaf physiological traits in dominant plants to artificial flooding, we intend to reveal the survival mechanisms of plants under adverse conditions and lay the foundation for vegetation restoration in the TGHFZ.

Multi-functional Chitosan Polymeric Micelles for improving the oral bioavailability of Paclitaxel based on synergistic effect.

A novel multi-functional micelle delivery system was developed for enhancing the oral absorption of paclitaxel (PTX). The delivery carriers were constructed by modifying chitosan-stearic acid (CS-SA) micelles with L-carnitine (LC) and co-encapsulating quercetin (Que), and the PTX-loaded micelles were prepared by film-sonication dispersing technique. The as-prepared micelles showed homogeneous spherical shapes with a small particle size of 148.3 ± 1.7 nm, high drug loading of 7.05% and low critical micelle concentration (CMC) of 16.89 µg/ml. Compared to the in-house PTX formulation similar to the commercial injection Taxol™, the target PTX-loaded micelles had obvious sustained-release effects and exhibited an oral relative bioavailability of 168.08%. The cellular uptake studies of Caco-2 cells confirmed the micellar modification of LC and the co-loading of Que played important roles in promoting the absorption of drug loaded in micelles. The CYP3A4 enzyme test demonstrated the micelles had an inhibitory effect on the metabolic enzyme due to the presence of Que. These findings confirmed the potential of the multi-functional chitosan polymeric micelles based on synergistic effect as an effective oral delivery system.

SPAK isoforms and OSR1 regulate sodium-chloride co-transporters in a nephron-specific manner.

STE20/SPS-1-related proline-alanine-rich protein kinase (SPAK) and oxidative stress-related kinase (OSR1) activate the potassium-dependent sodium-chloride co-transporter, NKCC2, and thiazide-sensitive sodium-chloride cotransporter, NCC, in vitro, and both co-localize with a kinase regulatory molecule, Cab39/MO25α, at the apical membrane of the thick ascending limb (TAL) and distal convoluted tubule (DCT). Yet genetic ablation of SPAK in mice causes a selective loss of NCC function, whereas NKCC2 becomes hyperphosphorylated. Here, we explore the underlying mechanisms in wild-type and SPAK-null mice. Unlike in the DCT, OSR1 remains at the TAL apical membrane of KO mice where it is accompanied by an increase in the active, phosphorylated form of AMP-activated kinase. We found an alterative SPAK isoform (putative SPAK2 form), which modestly inhibits co-transporter activity in vitro, is more abundant in the medulla than the cortex. Thus, enhanced NKCC2 phosphorylation in the SPAK knock-out may be explained by removal of inhibitory SPAK2, sustained activity of OSR1, and activation of other kinases. By contrast, the OSR1/SPAK/M025α signaling apparatus is disrupted in the DCT. OSR1 becomes largely inactive and displaced from M025α and NCC at the apical membrane, and redistributes to dense punctate structures, containing WNK1, within the cytoplasm. These changes are paralleled by a decrease in NCC phosphorylation and a decrease in the mass of the distal convoluted tubule, exclusive to DCT1. As a result of the dependent nature of OSR1 on SPAK in the DCT, NCC is unable to be activated. Consequently, SPAK(-/-) mice are highly sensitive to dietary salt restriction, displaying prolonged negative sodium balance and hypotension.

Air-mattress system for ballistocardiogram-based heart rate and breathing rate estimation.

Sleep-related problems are widespread. Numerous devices for sleep monitoring are increasingly available, including smartwatches, sleep monitoring rings, etc. These devices accumulate and analyze a substantial quantity of physiological data. In this study, we develop a smart air-mattress system that can effectively aid health measurements. The proposed system adopts an air-mattress system to detect subtle changes in pressure and thereby collect micro physiological signals, including ballistocardiography (BCG) and breathing signals. The system uses ultrasonic signals to detect the subject's turning movements. To increase the signal recognition accuracy, the BCG signal is processed effectively to reduce noise interference engendered by the body movement during sleep and is processed using regression analysis for heart rate and breathing rate estimation. Accordingly, the proposed system is unconstrained and can be used to collect micro BCG signals, breathing signals, heart rate signals, and turning movements for the long-term health-care.