[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.

Rewritable printing of ionic liquid nanofilm utilizing focused ion beam induced film wetting.

Manipulating liquid flow over open solid substrate at nanoscale is important for printing, sensing, and energy devices. The predominant methods of liquid maneuvering usually involve complicated surface fabrications, while recent attempts employing external stimuli face difficulties in attaining nanoscale flow control. Here we report a largely unexplored ion beam induced film wetting (IBFW) technology for open surface nanofluidics. Local electrostatic forces, which are generated by the unique charging effect of Helium focused ion beam (HFIB), induce precursor film of ionic liquid and the disjoining pressure propels and stabilizes the nanofilm with desired patterns. The IBFW technique eliminates the complicated surface fabrication procedures to achieve nanoscale flow in a controllable and rewritable manner. By combining with electrochemical deposition, various solid materials with desired patterns can be produced.

Prenatal diagnosis, pregnancy determination and follow up of sex chromosome aneuploidy screened by non-invasive prenatal testing from 122 453 unselected singleton pregnancies: A retrospective analysis of 7-year experience.

The phenotype of SCA patients are diversities, make prenatal counseling and parental decision-making following the prenatal diagnosis of SCA more complicated and challenging. NIPT has higher sensitivity and specificity in screening trisomy 21 syndrome, but the effectiveness of NIPT in detecting SCA is still controversial. This study is a large-scale retrospective cohort of positive SCA screened from unselected singleton pregnancies by non-invasive prenatal testing (NIPT) from a single prenatal center of a tertiary hospital. Clinical information, indications, diagnostic results, ultrasound findings, pregnancy determinations, and follow-up were reviewed and analyzed. 596 cases of SCA positive were screened out of 122 453, giving a positive detection rate of 0.49%. 510 cases (85.6%) conducted with amniocentesis to detect fetal chromosome, of which 236 were confirmed as true positive of SCA with PPV of 46.3% (236/510). Of the 236 cases confirmed as true positive SCA, 114 cases (48.3%)chose to terminate the pregnancy (93.0%, 65.3%, 15.4% and 10.9% for 45,X, 47,XXY, 47,XXX and 47,XYY, respectively), 122 cases (51.7%) elected to continue the pregnancy. In conclusions, NIPT as a first-tier routine method for screening autosomal aneuploidies, also could play an important role in screening SCA. Low-risk pregnant women are the main indication for the detection of SCA as NIPT test provides to non-selective population. For 47,XXX and 47,XYY with mild phenotype, couples would like to continue the pregnancy. But for 45,X and 47,XXY, parents apt to terminate pregnancy no matter ultrasound abnormalities were found or not.

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.

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.

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.

Update on the association of miR-149 rs2292832 C>T polymorphism with gastric cancer risk: A meta-analysis study of gastrointestinal cancers.

OBJECTIVE: Single nucleotide polymorphisms in microRNAs are believed to affect the occurrence and progression of cancer by altering the expression and biological functions of microRNAs. Several studies investigated the role of the miR-149 rs2292832 C>T polymorphism on the risk of gastric cancer (GC), but got conflicting results. METHODS: We performed a comprehensive and systematic search through the PubMed MEDLINE, Google Scholar, Science Direct, Scopus, CNKI, and Web of science, 8 studies were included in the meta-analysis to determine whether miR-149 rs2292832 C>T polymorphism contributed to the risk of GC. RESULTS: Pooled data indicated that miR-149 rs2292832 C>T polymorphism was not associated with GC risk. In the stratified analysis by ethnicity, miR-149 rs2292832 C>T polymorphism significantly increased GC risk under the allele comparison model (odds ratio [OR] = 1.27, 95% CI = 1.04-1.55, Pheterogeneity = 0.18, P = .02), recessive model (OR = 1.44, 95% CI = 1.04-2.01, Pheterogeneity = 0.19, P = .03) among Caucasians; but decreased GC risk under the allele comparison model (OR = 0.89, 95% CI = 0.81-0.98, Pheterogeneity = 0.22, P = .02) and dominant model (OR = 0.82, 95% CI = 0.72-0.93, Pheterogeneity = 0.15, P = .01) among Asian. CONCLUSION: Our meta-analysis suggests a positive correlation between miR-149 rs2292832 C>T polymorphism and GC development among Caucasians, but negative correlation among Asian population.

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 identification and characterization of a plant height and grain length related gene hfr131 in rice.

Plant height and grain size are important agronomic traits affecting rice yield. Various plant hormones participate in the regulation of plant height and grain size in rice. However, how these hormones cooperate to regulate plant height and grain size is poorly understood. In this study, we identified a brassinosteroid-related gene, hfr131, from an introgression line constructed using Oryza longistaminata, that caused brassinosteroid insensitivity and reduced plant height and grain length in rice. Further study showed that hfr131 is a new allele of OsBRI1 with a single-nucleotide polymorphism (G to A) in the coding region, leading to a T988I conversion at a conserved site of the kinase domain. By combining yeast one-hybrid assays, chromatin immunoprecipitation-quantitative PCR and gene expression quantification, we demonstrated that OsARF17, an auxin response factor, could bind to the promoter region of HFR131 and positively regulated HFR131 expression, thereby regulating the plant height and grain length, and influencing brassinosteroid sensitivity. Haplotype analysis showed that the consociation of OsAFR17Hap1 /HFR131Hap6 conferred an increase in grain length. Overall, this study identified hfr131 as a new allele of OsBRI1 that regulates plant height and grain length in rice, revealed that brassinosteroid and auxin might coordinate through OsARF17-HFR131 interaction, and provided a potential breeding target for improvement of rice yield.

Wearable, Sensing-Controlled, Ultrasound-Based Microneedle Smart System for Diabetes Management.

An intelligent closed-loop system that senses glucose and automatically delivers insulin can provide enhanced glycemic control for diabetes management. Here, we report for the first time on the development of a wearable, sensing-controlled, ultrasound-based closed-loop microneedle smart system for diabetes management. Polylactic acid (PLA) hollow microneedles were fabricated by soft lithography that can maintain excellent mechanical strength and stability in biofluids, followed by the deposition of sensing electrodes on the outer layer. An ultrasonic insulin pump was constructed by integrating a lead zirconate titanate piezoelectric (PZT) ring and a biocompatible stainless-steel sheet with hundreds of tapered holes on top of the inner layer of the microneedles. Both the sensor and the pump were powered and controlled by a printed circuit board (PCB). When the sensing device detects interstitial glucose levels above normal, the closed-loop control algorithm triggers the ultrasonic pump to deliver insulin into the interstitial fluid through the microneedle hollow channels of the PLA microneedles. The ultrasound from the pump can cause the vaporization of insulin in the subcutaneous tissue fluid, accelerate the diffusion rate, and improve the efficiency of insulin treatment and utilization. The system has successfully demonstrated effective control of glucose levels in diabetic rats. The glucose sensor showed a high sensitivity of 0.212 µA/mM at 0-28 mM with a detection limit of 14 µM, and the mean absolute relative difference (MARD) was 9.96% with an average error of 1.6 mM. The flow rate of the ultrasonic pump was 120 µL/min, and the glucose-lowering rate was 4 mM/h. This work may open a new paradigm for the development of intelligent systems for diabetes management, as well as a wide range of practical applications in diabetes patients.

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.

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.

A Microtube-Based Wearable Closed-Loop Minisystem for Diabetes Management.

Diabetes is a chronic metabolic disease with a high blood glucose level, leading to both seriously acute and chronic complications. The closed-loop system is an ideal system for diabetes management. However, the large size and high cost of the commercial systems restrict their widespread uses. Here, we present for the first time a microtube-based wearable closed-loop minisystem for diabetes management. The closed-loop minisystem includes a biosensing device, an electroosmotic micropump, and a printed circuit board (PCB) with an algorithm. The microtube-based sensing device coated on the outer surface of the microtube is inserted into subcutaneous tissue for detecting interstitial glucose; the current signal for sensing glucose is processed by the PCB to power the electroosmotic micropump intelligently for the delivery of insulin into the subcutaneous tissue via the microtube channel. The closed-loop minisystem worn on a diabetic SD rat can successfully maintain its blood glucose level within a safe level. It is expected that this new closed-loop paradigm could open up new prospects for clinical diabetes management.

Uric acid and creatinine biosensors with enhanced room-temperature storage stability by a multilayer enzyme matrix.

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.

A disposable printed amperometric biosensor for clinical evaluation of creatinine in renal function detection.

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.

MTRR rs1532268 polymorphism and gastric cancer risk: evidence from a meta-analysis.

OBJECTIVE: The methionine synthase reductase (MTRR) gene encodes the MTRR enzyme involved in the metabolic pathway of homocysteine. Several studies investigated the effect of the MTRR rs1532268 gene polymorphism on the risk of gastric cancer (GC), but the results have been inconsistent. METHODS: We performed a comprehensive and systematic search of PubMed, Google Scholar, MEDLINE, Science Direct, Scopus, CNKI, and Web of Science. Five studies were included in this meta-analysis to determine whether MTRR rs1532268 polymorphism contributes to the risk of GC. RESULTS: Pooled data indicated that the MTRR rs1532268 polymorphism significantly increased GC risk under the allele comparison model (odds ratio [OR] = 1.14, 95% confidence interval [CI] = 1.01-1.29) and dominant model (OR = 1.14, 95% CI = 1.00-1.30). In the analysis stratified by ethnicity, no relationship was found in Whites or Asians. CONCLUSION: Our meta-analysis suggests a positive correlation between MTRR rs1532268 polymorphism and GC development.

Closed-Loop Diabetes Minipatch Based on a Biosensor and an Electroosmotic Pump on Hollow Biodegradable Microneedles.

Developing a miniaturized, low-cost, and smart closed-loop system for diabetes could significantly improve life quality and benefit millions of people. Conventional closed-loop devices are large in size and exorbitant. Here, we unprecedentedly demonstrate an electrically controlled flexible closed-loop patch for continuous diabetes management by integrating hollow biodegradable microneedles with a biosensing device and an electroosmotic pump. The hollow microneedles were fabricated using a combination of soft lithography and micromachining. The outer layer of the microneedles was functionalized to serve as a biosensing device for the in situ sensitive and accurate monitoring of interstitial glucose. The inner layer of the microneedles was integrated with a flexible electroosmotic pump to deliver insulin, and the delivery rate was electrically controlled by the glucose level from the biosensing device. The closed-loop system successfully stabilized the blood glucose levels of diabetic rats in a normal and safe range. The system is painless, miniaturized, cost-effective, and flexible. It is anticipated that it could open up exciting new avenues for fundamental studies of new closed-loop devices as well as practical applications for diabetes management.