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In order to improve the living standards of diabetes patients and reduce the negative health effects of this disease, the medical community has been actively searching for more effective treatments. In recent years, an artificial pancreas has emerged as an important approach to managing diabetes. Despite these recent advances, meeting the requirements for miniaturized size, accurate sensing and large-volume pumping capability remains a great challenge. Here, we present a novel miniaturized artificial pancreas based on a long microtube sensor integrated with an ultrasonic pump. Our device meets the requirements of achieving both accurate sensing and high pumping capacity. The artificial pancreas is constructed based on a long microtube that is low cost, painless and simple to operate, where the exterior of the microtube is fabricated as a glucose sensor for detecting diabetes and the interior of the microtube is used as a channel for delivering insulin through an ultrasonic pump. This work successfully achieved closed-loop control of blood glucose and treatment of diabetes in rats. It is expected that this work can open up new methodologies for the development of microsystems, and advance the management approach for diabetes patients. [Display omitted] • We report a miniature artificial pancreas with accuracy and high pumping capacity. • The artificial pancreas is based on a long microtube sensor and an ultrasonic pump. • This work realized a closed-loop control of blood glucose levels in diabetic rats. [ABSTRACT FROM AUTHOR]

The development of novel diabetes monitoring sensors is important for the diabetes management of millions of diabetic patients. This work reports a flexible filamentary continuous glucose monitoring (CGM) sensor. A multilayer CGM sensor has been constructed on titanium filament with low cost and ease of use. The sensor, made of flexible material, offers better adaptability and comfort than traditional rigid filament CGM sensors, allowing continuous monitoring of subcutaneous blood glucose levels to provide patients with treatment strategies. The performance and reliability of the sensor were verified through rat experiments. The trend of the increase and decrease of the detected current was generally consistent with the actual blood glucose, and the detected values were located in regions A and B of the Clarke error grid. The results show that the sensor has the advantages of high sensitivity, high accuracy and fast response speed, which is suitable for monitoring the blood glucose level for a long time and has a broad application prospect in diabetes monitoring, exercise monitoring, health management and clinical application. [Display omitted] • This work reports a flexible filamentary continuous glucose monitoring (CGM) sensor. • A multilayer CGM sensor has been constructed on titanium filament with low cost and ease of use. • The performance of the sensor was verified through rat experiments with high reliability and accuracy. • The sensor has high sensitivity, high accuracy and fast response for monitoring interstitial glucose. [ABSTRACT FROM AUTHOR]

As the rapid development of medical devices, micropumps have received increasing and widespread attentions for a variety of healthcare applications. The ongoing challenges for developing the micropumps for healthcare applications are the working mechanisms of the pumps, the device configurations, and the fabrication approaches. To address these challenges, this review would explore the fundamental principles and practical aspects of the micropumps, including the types of the micropumps, their working principles, the manufacturing processes for constructing the micropumps, and the related biomedical applications and commercial products. This review can serve as a resouce for the construction of next-generation micropumps, as well as a wide range of biomedical applications ranging from the disease diagnosis to drug delivery. [Display omitted] [ABSTRACT FROM AUTHOR]

In clinical practice, sera creatinine level is regarded as a crucial biomarker for the diagnosis, staging and monitoring of kidney disease. An amperometric biosensor is rapid, accurate, and cost-effective, with a portability and a simple operation. Herein, we report for the firsttime a disposable, printed amperometric biosensor for the clinical evaluation of creatinine in renal function detection. The sensor is constructed based on Prussian blue/carbon-graphite paste as the working electrode and the immobilization of creatinine amidohydrolase, creatine amidinohydrolase and sarcosine oxidase. The creatinine biosensor shows a linear detection range from 0.05 to 1.4 mM with a detection time of about 3 min. In addition, the sensor shows a high stability that can maintain above 86% of the initial activity after being stored for over 4 months. Moreover, the sensor shows almost the same results as those with the Jaffe method for measuring the real blood samples. We anticipate that the creatinine biosensor could be widely used in the medical and healthcare areas, especially for at-home testing and onsite medical examinations. [Display omitted] • The work reports for the first time the development of a disposable, miniaturized and cost-effective creatinine biosensor. • The biosensor shows an accurate, sensitive and rapid determination of serum creatinine in renal function detection. • The biosensor demonstrates a similar detection performance to the Jeff Method that is used in hospital. • The biosensor exhibits a great potential for the at-home testing and the on-site medical examination. [ABSTRACT FROM AUTHOR]

Uric acid and creatinine are essential biomarkers for many diseases, such as gout, hyperuricemia, kidney diseases and heart diseases. Electrochemical biosensors are promising candidates for detecting uric acid and creatinine. However, the sensors always suffer from low stability that would limit their practical applications. In this work, we report a new multilayer enzyme matrix to enhance the room-temperature storage stabilities of uric acid and creatinine biosensors significantly. The enzymes are first dropped on the electrode surface directly, then a layer of glutaraldehyde was deposited on the surface of the enzyme layer, and after that, another layer of a polyvinyl alcohol (PVA)/poly(ethylene glycol) (PEG) composite was further placed on the surface of the glutaraldehyde layer, with drying in between. The stabilities of uric acid and creatinine biosensors were enhanced significantly, and the sensors can maintain highly stable sensing performance for over 4 months with a storage at room temperature. It is anticipated that this work could open new avenues for the practical applications of the uric acid and creatinine biosensors. [Display omitted] • The work reports a new multilayer enzyme matrix to enhance the room-temperature storage stabilities of biosensors. • The method is based on a sequential deposition of enzyme, glutaraldehyde, and polyvinyl alcohol/poly(ethylene glycol). • The sensors can maintain highly stable sensing performance for over 4 months with a storage at room temperature. • The sensors can perform accurate detection of uric acid and creatinine in whole blood samples. [ABSTRACT FROM AUTHOR]

Background: Yield and quality are the two most important traits in crop breeding. Exploring the regulatory mechanisms that affect both yield and quality traits is of great significance for understanding the molecular genetic networks controlling these key crop attributes. Expansins are cell wall loosening proteins that play important roles in regulating rice grain size. Results: We investigated the effect of OsEXPA7, encoding an expansin, on rice grain size and quality. OsEXPA7 overexpression resulted in increased plant height, panicle length, grain length, and thousand-grain weight in rice. OsEXPA7 overexpression also affected gel consistency and amylose content in rice grains, thus affecting rice quality. Subcellular localization and tissue expression analyses showed that OsEXPA7 is localized on the cell wall and is highly expressed in the panicle. Hormone treatment experiments revealed that OsEXPA7 expression mainly responds to methyl jasmonate, brassinolide, and gibberellin. Transcriptome analysis and RT-qPCR experiments showed that overexpression of OsEXPA7 affects the expression of OsJAZs in the jasmonic acid pathway and BZR1 and GE in the brassinosteroid pathway. In addition, OsEXPA7 regulates the expression of key quantitative trait loci related to yield traits, as well as regulates the expression levels of BIP1 and bZIP50 involved in the seed storage protein biosynthesis pathway. Conclusions: These results reveal that OsEXPA7 positively regulates rice yield traits and negatively regulates grain quality traits by involving plant hormone pathways and other trait-related pathway genes. These findings increase our understanding of the potential mechanism of expansins in regulating rice yield and quality traits and will be useful for breeding high-yielding and high-quality rice cultivars. [ABSTRACT FROM AUTHOR]

Objective: This study aims to perform a prenatal genetic diagnosis of a high-risk fetus with trisomy 7 identified by noninvasive prenatal testing (NIPT) and to evaluate the efficacy of different genetic testing techniques for prenatal diagnosis of trisomy mosaicism. Methods: For prenatal diagnosis of a pregnant woman with a high risk of trisomy 7 suggested by NIPT, karyotyping and chromosomal microarray analysis (CMA) were performed on an amniotic fluid sample. Low-depth whole-genome copy number variation sequencing (CNV-seq) and fluorescence in situ hybridization (FISH) were used to clarify the results further. In addition, methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) was performed to analyze the possibility of uniparental disomy(UPD). Results: Amniotic fluid karyotype analysis revealed a 46, XX result. Approximately 20% mosaic trisomy 7 was detected according to the CMA result. About 16% and 4% of mosaicism was detected by CNV-seq and FISH, respectively. MS-MLPA showed no methylation abnormalities. The fetal ultrasound did not show any detectable abnormalities except for mild intrauterine growth retardation seen at 39 weeks of gestation. After receiving genetic counseling, the expectant mother decided to continue the pregnancy, and follow-up within three months of delivery was normal. Conclusion: In high-risk NIPT diagnosis, a combination of cytogenetic and molecular genetic techniques proves fruitful in detecting low-level mosaicism. Furthermore, the exclusion of UPD on chromosome 7 remains crucial when NIPT indicates a positive prenatal diagnosis of trisomy 7. [ABSTRACT FROM AUTHOR]

Objective: To investigate factors associated with fetal fraction and to develop a new predictive method for low fetal fraction before noninvasive prenatal testing. Methods: The study was a retrospective cohort analysis based on the results of noninvasive prenatal testing, complete blood count, thyroxin test, and Down's syndrome screening during the first or second trimester in 14,043 pregnant women. Random forests algorithm was applied to predict the low fetal fraction status (fetal fraction < 4%) through individual information and laboratory records. The performance of the model was evaluated and compared to predictions using maternal weight. Results: Of 14,043 cases, maternal weight, red blood cell, hemoglobin, and free T3 were significantly negatively correlated with fetal fraction while gestation age, free T4, pregnancy-associated plasma protein-A, alpha-fetoprotein, unconjugated estriol, and β-human chorionic gonadotropin were significantly positively correlated with fetal fraction. Compared to predictions using maternal weight as an isolated parameter, the model had a higher area under the curve of receiver operating characteristic and overall accuracy. Conclusions: The comprehensive predictive method based on combined multiple factors was more effective than a single-factor model in low fetal fraction status prediction. This method can provide more pretest quality control for noninvasive prenatal testing. [ABSTRACT FROM AUTHOR]

RNA‐binding proteins (RBPs) are components of the post‐transcriptional regulatory system, but their regulatory effects on complex traits remain unknown. Using an integrated strategy involving map‐based cloning, functional characterizations, and transcriptomic and population genomic analyses, we revealed that RBP‐K (LOC_Os08g23120), RBP‐A (LOC_Os11g41890), and RBP‐J (LOC_Os10g33230) encode proteins that form an RBP‐A‐J‐K complex that negatively regulates rice yield‐related traits. Examinations of the RBP‐A‐J‐K complex indicated RBP‐K functions as a relatively non‐specific RBP chaperone that enables RBP‐A and RBP‐J to function normally. Additionally, RBP‐J most likely affects GA pathways, resulting in considerable increases in grain and panicle lengths, but decreases in grain width and thickness. In contrast, RBP‐A negatively regulates the expression of genes most likely involved in auxin‐regulated pathways controlling cell wall elongation and carbohydrate transport, with substantial effects on the rice grain filling process as well as grain length and weight. Evolutionarily, RBP‐K is relatively ancient and highly conserved, whereas RBP‐J and RBP‐A are more diverse. Thus, the RBP‐A‐J‐K complex may represent a typical functional model for many RBPs and protein complexes that function at transcriptional and post‐transcriptional levels in plants and animals for increased functional consistency, efficiency, and versatility, as well as increased evolutionary potential. Our results clearly demonstrate the importance of RBP‐mediated post‐transcriptional regulation for the diversity of complex traits. Furthermore, rice grain yield and quality may be enhanced by introducing various complete or partial loss‐of‐function mutations to specific RBP genes using clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR‐associated protein 9 technology and by exploiting desirable natural tri‐genic allelic combinations at the loci encoding the components of the RBP‐A‐J‐K complex through marker‐assisted selection. [ABSTRACT FROM AUTHOR]

Amylose content (AC) is the main factor determining the palatability, viscosity, transparency, and digestibility of rice (Oryza sativa) grains. AC in rice grains is mainly controlled by different alleles of the Waxy (Wx) gene. The AP2/EREBP transcription factor OsEBP89 interacts with the MYC‐like protein OsBP5 to synergistically regulate the expression of Wx. Here, we determined that the GLYCOGEN SYNTHASE KINASE 5 (OsGSK5, also named SHAGGY‐like kinase 41 [OsSK41]) inhibits the transcriptional activation activity of OsEBP89 in rice grains during amylose biosynthesis. The loss of OsSK41 function enhanced Wx expression and increased AC in rice grains. By contrast, the loss of function of OsEBP89 reduced Wx expression and decreased AC in rice grains. OsSK41 interacts with OsEBP89 and phosphorylates four of its sites (Thr‐28, Thr‐30, Ser‐238, and Thr‐257), which makes OsEBP89 unstable and attenuates its interaction with OsBP5. Wx promoter activity was relatively weak when regulated by the phosphomimic variant OsEBP89E–OsBP5 but relatively strong when regulated by the nonphosphorylatable variant OsEBP89A–OsBP5. Therefore, OsSK41‐mediated phosphorylation of OsEBP89 represents an additional layer of complexity in the regulation of amylose biosynthesis during rice grain development. In addition, our findings provide four possible sites for regulating rice grain AC via precise gene editing. [ABSTRACT FROM AUTHOR]

Heading date is an important agronomic trait in rice (Oryza sativa L.). We previously fine‐mapped two complementary genes, Late Heading Date 1 and Late Heading Date 2 (LH2), that control the late heading trait in rice. Here, we cloned and analyzed the function of LH2. LH2 was fine‐mapped to a 53‐kb genomic region. Sequencing analysis revealed that there were differences in the coding sequence of LOC_Os08g07740 between the varieties 'Bo B' and 'Yuefeng B'. Therefore, LOC_Os08g07740 was identified as a candidate gene for LH2 and subsequently determined that LH2 is a Type 3 allele of Days To Heading 8. Transgenic plants of Yuefeng B carrying LH2 from Bo B significantly delayed the heading date under short‐day and long‐day conditions. A yeast two‐hybrid analysis revealed that LH2 physically interacted with Heme Activator Protein (HAP) 5A, ‐H, ‐I, ‐L, ‐K, and HAP5‐LIKE. The HAP5 domain of HAP5 family members has various functions. Further analysis revealed that LH2 represses photoperiodic flowering by controlling the expression of Early Heading Date 1, Heading date 3a, and Rice Flowering Locus T1 in rice. Core Ideas: LH2 delayed heading by 17.6 d in short‐day conditions and >32.7 d in long‐day conditions.LH2 physically interacted with HAP5A, ‐H, ‐I, ‐L, ‐K, and HAP5‐LIKE.The HAP5 domain of the HAP5 family exhibited functional differentiation.LH2 is a Type 3 allele of DTH8. [ABSTRACT FROM AUTHOR]

Background: Down syndrome (DS) is a chromosomal disorder caused by a third copy of all or part of chromosome 21. Clinical observations and preclinical studies both suggest that DS may be associated with significant metabolic and bioenergetic alterations. But the metabolic alterations in pregnant women carrying DS fetuses still remains unclear. In this study, we investigated the characteristic metabolomics and lipidomics changes during fetal development of DS.Methods: The AF and random urine specimens were selected from 20 pregnant women carrying DS fetuses and 20 pregnant women carrying healthy fetuses. The diagnosis of DS was screened according to chromosome karyotype analysis, and untargeted metabolomic and lipidomic analyses were performed.Results: Through the analyses of AF, 308 differential metabolites were selected between DS and controls. The metabolites with significant changes mainly involved lipid molecules, organic acids, nucleotides and carbon. Further analysis of lipidomics showed 64 differential metabolites, mainly involving glycerides, sphingolipids and glycerolipids. As for urine metabolomic and lipidomic analyses, there existed consistent metabolites with AF, but the number was much less.Conclusions: Compared with the controls, carbon metabolism, amino acid metabolism, glyceride metabolism, sphingolipid metabolism and glycerophospholipid metabolism were significantly changed in DS cases. In addition, characterized biomarkers in AF and urine were screened for DS diagnosis, and these metabolites were mainly involved in energy metabolism and liver dysfunction. This finding may help improve the efficiency of prenatal screening for DS. [ABSTRACT FROM AUTHOR]

Developing methods for increasing the biomass and improving the plant architecture is important for crop improvement. We herein describe a gene belonging to the RING_Ubox (RING (Really Interesting New Gene) finger domain and U-box domain) superfamily, PLANT ARCHITECTURE and GRAIN NUMBER 1 (PAGN1), which regulates the number of grains per panicle, the plant height, and the number of tillers. We used the CRISPR/Cas9 system to introduce loss-of-function mutations to OsPAGN1. Compared with the control plants, the resulting pagn1 mutant plants had a higher grain yield because of increases in the plant height and in the number of tillers and grains per panicle. Thus, OsPAGN1 may be useful for the genetic improvement of plant architecture and yield. An examination of evolutionary relationships revealed that OsPAGN1 is highly conserved in rice. We demonstrated that OsPAGN1 can interact directly with OsCNR10 (CELL NUMBER REGULATOR10), which negatively regulates the number of rice grains per panicle. A transcriptome analysis indicated that silencing OsPAGN1 affects the levels of active cytokinins in rice. Therefore, our findings have clarified the OsPAGN1 functions related to rice growth and grain development. [ABSTRACT FROM AUTHOR]