Alternative splicing of lncRNA LAIR fine-tunes the regulation of neighboring yield-related gene LRK1 expression in rice.

The diversity in alternative splicing of long noncoding RNAs (lncRNAs) poses a challenge for functional annotation of lncRNAs. Moreover, little is known on the effects of alternatively spliced lncRNAs on crop yield. In this study, we cloned nine isoforms resulting from the alternative splicing of the lncRNA LAIR in rice. The LAIR isoforms are generated via alternative 5'/3' splice sites and different combinations of specific introns. All LAIR isoforms activate the expression of the neighboring LRK1 gene and enhance yield-related rice traits. In addition, there are slight differences in the binding ability of LAIR isoforms to the epigenetic modification-related proteins OsMOF and OsWDR5, which affect the enrichment of H4K16ac and H3K4me3 at the LRK1 locus, and consequently fine-tune the regulation of LRK1 expression and yield-related traits. These differences in binding may be caused by polymorphic changes to the RNA secondary structure resulting from alternative splicing. It was also observed that the composition of LAIR isoforms was sensitive to abiotic stress. These findings suggest that the alternative splicing of LAIR leads to the formation of a functional transcript population that precisely regulates yield-related gene expression, which may be relevant for phenotypic polymorphism-based crop breeding under changing environmental conditions.

Prenatal diagnosis of a trisomy 7 mosaic case: CMA, CNV-seq, karyotyping, interphase FISH, and MS-MLPA, which technique to choose?

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.

OsPDCD5 negatively regulates plant architecture and grain yield in rice.

Plant architecture is an important agronomic trait that affects crop yield. Here, we report that a gene involved in programmed cell death, OsPDCD5, negatively regulates plant architecture and grain yield in rice. We used the CRISPR/Cas9 system to introduce loss-of-function mutations into OsPDCD5 in 11 rice cultivars. Targeted mutagenesis of OsPDCD5 enhanced grain yield and improved plant architecture by increasing plant height and optimizing panicle type and grain shape. Transcriptome analysis showed that OsPDCD5 knockout affected auxin biosynthesis, as well as the gibberellin and cytokinin biosynthesis and signaling pathways. OsPDCD5 interacted directly with OsAGAP, and OsAGAP positively regulated plant architecture and grain yield in rice. Collectively, these findings demonstrate that OsPDCD5 is a promising candidate gene for breeding super rice cultivars with increased yield potential and superior quality.

Post-transcriptional regulation of grain weight and shape by the RBP-A-J-K complex in rice.

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.

[Analysis of clinical characteristics and molecular genetics in eighteen patients with 1q21.1 microdeletion syndrome].

OBJECTIVE: To explore the clinical characteristics of 1q21.1 microdeletion by using single nucleotide polymorphism microarrays (SNP array). METHODS: Eighteen cases of 1q21.1 microdeletion syndrome diagnosed at the Longgang District Maternal and Child Health Care Hospital of Shenzhen City from June 2017 to December 2022 were selected as the study subjects. Clinical data of the patients were collected. Results of chromosomal karyotyping and SNP assay were retrospectively analyzed. RESULTS: Among the 18 cases with 1q21.1 microdeletions, 13 had a deletion between BP3 and BP4, 4 had a deletion between BP1/BP2 and BP4, whilst 1 had a proximal 1q21.1 deletion (between BP2 and BP3) involving the Thrombocytopenia-absent radius (TAR) region. The deletions had spanned from 360 kb to 3.9 Mb, which encompassed the GJA5, GJA8, CHD1L, RBM8AB and other morbid genes. In three families, the proband child has inherited the same 1q21.1 microdeletion from their parents, whose clinical phenotype was normal or slightly abnormal. The clinical phenotypes of 1q21.1 microdeletion had included cognitive or behavioral deficits in 9 cases (9/18, 50.0%), growth retardation in 8 cases (8/18, 44.4%), craniofacial deformities in 7 cases (7/18, 38.8%), cardiovascular malformations in 5 cases (5/18, 27.8%), and microcephaly in 3 cases (3/18, 16.7%). CONCLUSION: 1q21.1 microdeletion syndrome has incomplete penetrance and varied expression such as intellectual impairment, growth and development delay, and microcephaly, with a wide range of non-specific phenotypes.

A Natural Variation in PLEIOTROPIC DEVELOPMENTAL DEFECTS Uncovers a Crucial Role for Chloroplast tRNA Modification in Translation and Plant Development.

The modification of tRNA is important for accurate, efficient protein translation. A number of tRNA-modifying enzymes were found to influence various developmental processes in distinct organisms. However, few genetic or molecular studies have focused on genes encoding tRNA-modifying enzymes in green plant organelles. Here, we discovered that PDD OL , a natural variation allele of PLEIOTROPIC DEVELOPMENTAL DEFECTS (PDD), leads to pleiotropic developmental defects in a near-isogenic line (NIL) generated by introgressing the wild rice Oryza longistaminata into the rice (Oryza sativa) cv 187R. Map-based cloning revealed that PDD encodes an evolutionarily conserved tRNA-modifying GTPase belonging to the tRNA modification E family. The function of PDD was further confirmed by genetic complementation experiments and mutant analysis. PDD mRNA is primarily expressed in leaves, and PDD is localized to chloroplasts. Biochemical analyses indicated that PDD187R forms homodimers and has strong GTPase activity, whereas PDDOL fails to form homodimers and has weak GTPase activity. Liquid chromatography-coupled tandem quadrupole mass spectrometry revealed that PDD is associated with the 5-methylaminomethyl-2-thiouridine modification of chloroplast tRNA. Furthermore, compared to 187R, NIL-PDD OL has severely reduced levels of proteins involved in photosynthesis and ribosome biogenesis but increased levels of plastid-encoded RNA polymerase subunits. Finally, we demonstrate that the defect due to PDD OL alters chloroplast gene expression, thereby affecting communication between the chloroplast and the nucleus.

Microneedles: materials, fabrication, and biomedical applications.

The microneedles have attracted great interests for a wide range of transdermal biomedical applications, such as biosensing and drug delivery, due to the advantages of being painless, semi-invasive, and sustainable. The ongoing challenges are the materials and fabrication methods of the microneedles in order to obtain a specific shape, configuration and function of the microneedles to achieve a target biomedical application. Here, this review would introduce the types of materials of the microneedles firstly. The hardness, Young's modulus, geometric structure, processability, biocompatibility and degradability of the microneedles are explored as well. Then, the fabrication methods for the solid and hollow microneedles in recent years are reviewed in detail, and the advantages and disadvantages of each process are analyzed and compared. Finally, the biomedical applications of the microneedles are reviewed, including biosensing, drug delivery, body fluid extraction, and nerve stimulation. It is expected that this work provides the fundamental knowledge for developing new microneedle devices, as well as the applications in a variety of biomedical fields.

RNA-Seq Transcriptome Analysis and Evolution of OsEBS, a Gene Involved in Enhanced Spikelet Number per Panicle in Rice.

Spikelet number per panicle (SNP) is one of the most important yield components in rice. Rice ENHANCING BIOMASS AND SPIKELET NUMBER (OsEBS), a gene involved in improved SNP and yield, has been cloned from an accession of Dongxiang wild rice. However, the mechanism of OsEBS increasing rice SNP is poorly understood. In this study, the RNA-Seq technology was used to analyze the transcriptome of wildtype Guichao 2 and OsEBS over-expression line B102 at the heading stage, and analysis of the evolution of OsEBS was also conducted. A total of 5369 differentially expressed genes (DEGs) were identified between Guichao2 and B102, most of which were down-regulated in B102. Analysis of the expression of endogenous hormone-related genes revealed that 63 auxin-related genes were significantly down-regulated in B102. Gene Ontogeny (GO) enrichment analysis showed that the 63 DEGs were mainly enriched in eight GO terms, including auxin-activated signaling pathway, auxin polar transport, auxin transport, basipetal auxin transport, and amino acid transmembrane transport, most of which were directly or indirectly related to polar auxin transport. Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic pathway analysis further verified that the down-regulated genes related to polar auxin transport had important effects on increased SNP. Analysis of the evolution of OsEBS found that OsEBS was involved in the differentiation of indica and japonica, and the differentiation of OsEBS supported the multi-origin model of rice domestication. Indica (XI) subspecies harbored higher nucleotide diversity than japonica (GJ) subspecies in the OsEBS region, and XI experienced strong balancing selection during evolution, while selection in GJ was neutral. The degree of genetic differentiation between GJ and Bas subspecies was the smallest, while it was the highest between GJ and Aus. Phylogenetic analysis of the Hsp70 family in O. sativa, Brachypodium distachyon, and Arabidopsis thaliana indicated that changes in the sequences of OsEBS were accelerated during evolution. Accelerated evolution and domain loss in OsEBS resulted in neofunctionalization. The results obtained from this study provide an important theoretical basis for high-yield rice breeding.

The kinase OsSK41/OsGSK5 negatively regulates amylose content in rice endosperm by affecting the interaction between OsEBP89 and OsBP5.

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.

Auxin signaling module OsSK41-OsIAA10-OsARF regulates grain yield traits in rice.

Auxin is an important phytohormone in plants, and auxin signaling pathways in rice play key roles in regulating its growth, development, and productivity. To investigate how rice grain yield traits are regulated by auxin signaling pathways and to facilitate their application in rice improvement, we validated the functional relationships among regulatory genes such as OsIAA10, OsSK41, and OsARF21 that are involved in one of the auxin (OsIAA10) signaling pathways. We assessed the phenotypic effects of these genes on several grain yield traits across two environments using knockout and/or overexpression transgenic lines. Based on the results, we constructed a model that showed how grain yield traits were regulated by OsIAA10 and OsTIR1, OsAFB2, and OsSK41 and OsmiR393 in the OsSK41-OsIAA10-OsARF module and by OsARF21 in the transcriptional regulation of downstream auxin response genes in the OsSK41-OsIAA10-OsARF module. The population genomic analyses revealed rich genetic diversity and the presence of major functional alleles at most of these loci in rice populations. The strong differentiation of many major alleles between Xian/indica and Geng/japonica subspecies and/or among modern varieties and landraces suggested that they contributed to improved productivity during evolution and breeding. We identified several important aspects associated with the genetic and molecular bases of rice grain and yield traits that were regulated by auxin signaling pathways. We also suggested rice auxin response factor (OsARF) activators as candidate target genes for improving specific target traits by overexpression and/or editing subspecies-specific alleles and by searching and pyramiding the 'best' gene allelic combinations at multiple regulatory genes in auxin signaling pathways in rice breeding programs.

A New RING Finger Protein, PLANT ARCHITECTURE and GRAIN NUMBER 1, Affects Plant Architecture and Grain Yield in Rice.

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.

[Clinical characteristics and prenatal diagnosis of fetuses with sex chromosomal aneuploidies detected by non-invasive prenatal testing during early and midterm pregnancies].

OBJECTIVE: To analyze the indication, karyotyping result, ultrasound finding, pregnancy decision and follow-up of fetuses with sex chromosome aneuploidies (SCA) detected by non-invasive prenatal testing (NIPT) during early and midterm pregnancies. METHODS: The results of 225 singleton pregnancies with fetal SCA detected by NIPT were reviewed and analyzed. RESULTS: The 225 cases included 45,X (n=37), 47,XXY (n=74), 47,XXX (n=50), 47,XYY (n=56) and mosaicisms (n=8), among which 121 (53.8%) have opted to terminate the pregnancy, including 45,X (n=31), 47,XXY (n=61), 47,XXX (n=14), 47,XYY (n=12) and 3 mosaicisms. The remainder 104 (46.2%) have elected to continue with the pregnancy, among which three have opted to terminate due to abnormalities detected by ultrasonography, and two had spontaneous abortions. CONCLUSION: NIPT as a first-tier screening method can effectively detect fetal trisomies 21, 13 and 18 as well as SCA. The types of fetal SCA and presence of ultrasound abnormalities are critical factors for the termination of pregnancy.

A Smart Tongue Depressor-Based Biosensor for Glucose.

The development of new bioelectronic platforms for direct interactions with oral fluid could open up significant opportunities for healthcare monitoring. A tongue depressor is a widely used medical tool that is inserted into the mouth, where it comes into close contact with saliva. Glucose is a typical salivary biomarker. Herein, we report-for the first time-a tongue depressor-based biosensor for the detection of glucose in both phosphate buffer and real human saliva. Carbon nanotubes (CNTs) are attractive electronic materials, with excellent electrochemical properties. The sensor is constructed by printing CNTs and silver/silver chloride (Ag/AgCl) to form three electrodes in an electrochemical cell: Working, reference, and counter electrodes. The enzyme glucose oxidase (GOD) is immobilized on the working electrode. The glucose detection performance of the sensor is excellent, with a detection range of 7.3 µM to 6 mM. The glucose detection time is about 3 min. The discretion between healthy people's and simulated diabetic patients' salivary samples is clear and easy to tell. We anticipate that the biosensor could open up new opportunities for the monitoring of salivary biomarkers and advance healthcare applications.

Fine mapping of a major quantitative trait locus, qgnp7(t), controlling grain number per panicle in African rice (Oryza glaberrima S.).

Grain number per panicle is a major component of rice yield that is typically controlled by many quantitative trait loci (QTLs). The identification of genes controlling grain number per panicle in rice would be valuable for the breeding of high-yielding rice. The Oryza glaberrima chromosome segment substitution line 9IL188 had significantly smaller panicles compared with the recurrent parent 9311. QTL analysis in an F2 population derived from a cross between 9IL188 and 9311 revealed that qgnp7(t), a major QTL located on the short arm of chromosome 7, was responsible for this phenotypic variation. Fine mapping was conducted using a large F3 population containing 2250 individuals that were derived from the F2 heterozygous plants. Additionally, plant height, panicle length, and grain number per panicle of the key F4 recombinant families were examined. Through two-step substitution mapping, qgnp7(t) was finally localized to a 41 kb interval in which eight annotated genes were identified according to available sequence annotation databases. Phenotypic evaluation of near isogenic lines (NIL-qgnp7 and NIL-qGNP7) indicated that qgnp7(t) has pleiotropic effects on rice plant architecture and panicle structure. In addition, yield estimation of NILs indicated that qGNP7(t) derived from 9311 is the favorable allele. Our results provide a foundation for isolating qgnp7(t). Markers flanking this QTL will be a useful tool for the marker-assisted selection of favorable alleles in O. glaberrima improvement programs.

A Tube-Integrated Painted Biosensor for Glucose and Lactate.

Developing a simple and direct approach for sensitive, specific, and rapid detection of metabolic compounds is of great importance for a variety of biological, medical, and food applications. Tubes are a highly portable and accessible container shape which are widely used for scientific research in cell biology and chemical synthesis, and which are also of great use in domestic health care applications. Here, we show for the first time the development of a tube-based painted amperometric biosensor for the detection of glucose and lactate. The sensor was prepared by printing carbon graphite and silver/silver chloride inks on the interior wall of the tube and then immobilizing glucose oxidase or lactate oxidase on the sensor. The sensor showed a sensitive, rapid, and reliable detection of glucose and lactate. We anticipate that these results could open new avenues for the development of painted biosensors, and toward advanced biosensor applications.

Wearable Carbon Nanotube-Based Biosensors on Gloves for Lactate.

Developing a simple and direct approach for interfacing a sensor and a target analyte is of great interest for fields such as medical diagnosis, threat detection, food quality control, and environmental monitoring. Gloves provide a unique interface for sensing applications. Here, we show for the first time the development of wearable carbon nanotube (CNT)-based amperometric biosensors painted onto gloves as a new sensing platform, used here for the determination of lactate. Three sensor types were studied, configured as: two CNT electrodes; one CNT electrode, and an Ag/AgCl electrode, and two CNT electrodes and an Ag/AgCl electrode. The sensors are constructed by painting the electrodes using CNT or Ag/AgCl inks. By immobilizing lactate oxidase onto the CNT-based working electrodes, the sensors show sensitive detections of lactate. Comparison of sensor performance shows that a combination of CNT and Ag/AgCl is necessary for highly sensitive detection. We anticipate that these findings could open exciting avenues for fundamental studies of wearable bioelectronics, as well as practical applications in fields such as healthcare and defense.

Gene expression profiling of flag leaves at the booting stage in the japonica hybrid rice Huayou14 and its parental lines by microarray.

Gene expression profiling using microarray has contributed significantly to heterosis studies. Using the Affymetrix rice genome array, we investigated gene expression profiles in the flag leaves of the japonica hybrid rice Huayou14 and its parental cultivars Shen9A and Fan14 at the booting stage. A total of 2057 genes differentially expressed (fold change ≥2 or ≤0.5) between Huayou14 and its parents were identified. Functional classification of the differentially expressed genes by Gene Ontology (GO) analysis indicated the differentially expressed genes were significantly enriched in photosynthesis-related cellular component categories (e.g. photosystem Ⅰ, chloroplast membrane and chloroplast envelope), and biological process categories (e.g. chlorophyll catabolic, chlorophyll biosynthetic and carotenoid biosynthetic processes). These results suggest that the changes in the photosynthetic ability of the japonica hybrid rice Huayou14 may be related to heterosis. Metabolic pathway analysis indicated that differentially expressed genes were significantly enriched in photosynthesis-antenna proteins and starch and sucrose metabolic pathways, instead of photosynthesis and carbon fixation pathways as reported previously. These results suggest that different genes or metabolic pathways might contribute to the heterosis of different hybrid combinations.

Wearable filamentary continuous sensor for interstitial glucose detection in diabetes management.

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.

An intelligent wearable artificial pancreas patch based on a microtube glucose sensor and an ultrasonic insulin pump.

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.