Search

Abstract Objective Analyze the ultrasound findings, single nucleotide polymorphism array (SNP-array) results, and pregnancy outcomes of fetuses with 7q11.23 deletions and duplications in the second and third trimesters. Investigate the prenatal ultrasound characteristics and follow up information of these fetuses. Methods Seven fetuses were diagnosed with 7q11.23 deletion and six with 7q11.23 duplication via SNP-array at the prenatal diagnosis center of a single Chinese tertiary medical center from January 2017 to May 2024. Maternal demographics, ultrasound findings, SNP-array results, pregnancy outcomes, and follow-up information were comprehensively reviewed and analyzed. Results The copy number variations (CNVs) ranged from 1.43 Mb to 1.78 Mb in cases of 7q11.23 deletions and from 1.42 Mb to 1.68 Mb in cases of 7q11.23 duplications. These CNVs encompassed 29 OMIM-listed genes, including ELN, DNAJC30, GTF2IRD1, and GTF2I. Among the seven cases of 7q11.23 deletion syndrome, six exhibited ultrasound abnormalities. The main clinical phenotypes included three cases of intrauterine growth restriction and four cases of cardiovascular system abnormalities, specifically two cases with ventricular septal defects, one case with aortic narrowing, and one case with supravalvular pulmonary stenosis. One case was particularly notable, exhibiting complex multi-organ structural malformations. Out of six cases of 7q11.23 duplication syndrome, five exhibited ultrasound abnormalities. These included two cases of cardiovascular abnormalities: one case with a widened left ventricle and another case with a shortened fetal humerus length. One case revealed complex multi-organ structural malformations, including hydronephrosis, a microgallbladder, and a cleft lip and palate. All seven cases of 7q11.23 deletions and three cases of 7q11.23 duplications opted for termination of the pregnancy. The remaining three cases of 7q11.23 duplications chose to continue the pregnancy. One case underwent surgical treatment for a ventricular septal defect after birth, and the prognosis was favorable. Another case involved a full-term delivery, this child was followed up at the age of 4 and exhibited a phenotype of poor language expression ability. Conclusion Our study broadened the clinical phenotype spectrum of fetuses with 7q11.23 deletions and duplications. Additionally, it conducted a preliminary evaluation of prenatal ultrasound findings and postnatal clinical phenotypes in follow-up cases. The clinical phenotype of fetuses with 7q11.23 deletion and duplication syndromes involves multiple systems and is relatively complex. Cardiovascular abnormalities and intrauterine growth restriction are the most common clinical manifestations observed in prenatal 7q11.23 deletion syndrome. Fetuses with 7q11.23 duplications exhibit a wide range of clinical phenotypes that lack specificity.

Abstract The persistent infection of high-risk human papillomavirus (HPV) and the progression of cervical cancer necessitate the involvement of microenvironmental immunity. As cervical lesions advance, there is an observed increase in the infiltration of type 2 (M2) macrophages. However, the precise mechanism driving this increased infiltration of M2 macrophages remains unclear. In this study, we investigated the role of exosomes in polarising M2 macrophages in cervical lesions associated with HPV E6. Through the analysis of bioinformatics data and clinical specimens, we discovered a positive correlation between HPV E6/E7 mRNA copy number and the level of M2 macrophage infiltration. Exosomes derived from HPV E6 overexpressed (HPV E6+) cervical squamous cell carcinoma (CESC) cells were found to induce the polarisation of macrophages towards M2 type. Specifically, miR-204-5p, enriched in HPV E6 + CESC exosomes, was transported into macrophages and triggered M2 macrophage polarisation by inhibiting JAK2. The clinical relevance of exosomal miR-204-5p in the progression of cervical lesions was validated through serum samples from 35 cases. Exosomal miR-204-5p emerges as a critical factor influencing M2 macrophage polarisation and is correlated with the severity of cervical lesions. Consequently, miR-204-5p could be used as a potential treatment and a candidate biomarker for cervical lesions.

Background This study aimed to evaluate the efficiency of noninvasive prenatal screening (NIPS) technology in screening for microdeletions in the 7q11.23 region.Methods 19,607 pregnant women underwent NIPS in our hospital. Maternal peripheral cell-free foetal DNA (cffDNA) was routinely screened for aneuploidy by cffDNA enrichment and simultaneously analyzed for pathogenic copy number variants (CNVs). The Williams syndrome (WS) 7q11.23 region was targeted in this study. Chromosomal microarray analysis (CMA) was used to verify the screen-positive samples.Results The mean concentration of cffDNA before and after enrichment increased from 9.44% to 19.32%, with a statistically significant difference. Two out of 19,607 samples tested for CNVs were found to have a heterozygous deletion at the 7q11.23 region, indicating a high risk for WS. CMA results confirmed the 1.5 megabase (Mb) deletions at the 7q11.23 region in amniotic fluid samples. One of the two WS foetuses had a small left ventricle by ultrasound screening, and the other did not have a significant cardiovascular abnormality phenotype.Conclusions NIPS screening for Williams syndrome can be achieved by enriching cell-free foetal DNA and improving bioinformatic analysis algorithms.

Abstract 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 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 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.

Grain size, characterized by a combination of grain length, width, and thickness, is one of the major determinants of yield in rice. The present study identified TATA-box binding protein-associated factor 2 (TAF2) as an essential component regulating transcription and determining grain size in rice. Map-based cloning showed that a G/T substitution in TAF2 resulted in a naturally occurring mutant called reduced grain size and plant height 1 (rgh1). The mutants, with weak edited rgh1 alleles, exhibited a small grain phenotype with reduced grain length and width, while the severe knockout mutant (rgh1-2s) was dwarf and completely sterile. Allelic test performed between rgh1 and several edited alleles confirmed that the mutation in TAF2 caused the rgh1 phenotype. GUS staining showed that TAF2 was mainly expressed in the vascular bundles of roots, stems, leaves, and grains. The cytological analysis revealed that reduced cell division in the glumes resulted in the small grain phenotype of rgh1. Further RNA-sequencing detected altered expression of genes involved in the basic biological processes in rgh1 mutant. These findings provide novel insights into the TAF2-mediated genetic mechanism regulating grain size 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.

Diabetes is a highly prevalent and chronic metabolic disease with a multifactorial etiology and various clinical manifestations. The point-of-care sensing platforms, as miniaturized devices being portable or worn on the body, are ideal approaches for monitoring diabetes, and can significantly improve the life qualities of diabetes patients with great convenience and comfort. In recent years, there have been many attempts for developing these miniaturized platforms. To successfully develop a point-of-care sensing platform for diabetes, there are several interesting questions: What are the mechanisms for sensing diabetes? How many biofluids are there for monitoring diabetes? Which type of biofluids could provide an accurate detection? What are the configurations of the sensing devices for each type of biofluid? Which is the current status for the development of the sensing devices? Which are the commercial devices for monitoring diabetes? This review will highlight our early attempts for addressing these questions. We believe this review could open up exciting opportunities for the development of the next-generation sensing devices for monitoring diabetes, as well as providing the diagnosis and monitoring methods for diabetes patients.

Abstract Diabetes is a prevalent chronic metabolic disease with multiple clinical manifestations and complications, and it is among the leading causes of death. Painless and continuous monitoring of interstitial glucose is highly desirable for diabetes management. Here we unprecedentedly show continuous monitoring of diabetes with an integrated microneedle biosensing device. The device was manufactured with a 3D printing process, a microfabrication process, an electroplating process, and an enzyme immobilization step. The device was inserted into the dermis layer of mouse skin and showed accurate sensing performance for monitoring subcutaneous glucose levels in normal or diabetic mice. The detection results were highly correlated with those obtained from a commercial blood glucose meter. We anticipate that the study could open exciting avenues for monitoring and managing diabetes, alongside fundamental studies of subcutaneous electronic devices.

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.

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.

The development of a low-cost and portable integrated sensing system for hydrogen peroxide could offer exciting opportunities for the diagnosis of diseases, and environmental monitoring. Arduino is a popular platform with integrated software and hardware, and a large number of open source sensor libraries. Here, we show the development of a new homemade Arduino-based potentiostat and its sensing of hydrogen peroxide. The Arduino-based potentiostat are made with a low cost, and a great flexibility. The new system can successfully perform the chronoamperometry and cyclic voltammetry functions. The system shows an accurate and precise sensing of hydrogen peroxide, and the detection performance of this system is almost the same as that from a commercial potentiostat. We anticipate that the study can open new routes for constructing a variety of electrochemical sensing systems, and towards advanced medical and environmental applications.

Rice (Oryza sativa L.) is a major food crop worldwide. Plant height and yield are important agronomic traits of rice. Several genes regulating plant height and/or yield have been cloned. However, the molecular mechanisms coordinating plant height and yield are not fully characterized. Here, we report a novel gene, OstMAPKKK5 that encodes a truncated variant of a mitogen-activated protein kinase kinase kinase 5 (OsMAPKKK5) lacking an intact kinase domain. Transgenic plants overexpressing OstMAPKKK5 in indica cultivar 9311 showed increased plant height, grain length, grain width, 1000-grain weight, grain number per main panicle, and yield. Real-time quantitative PCR showed that OstMAPKKK5 was widely expressed in various tissues and developmental stages. The increased plant height and yield were attributed to enlarged cell size. Overexpression of OstMAPKKK5 led to higher contents of various forms of endogenous gibberellin (GA), especially the most common active forms, GA1, GA3, GA4. We concluded that OstMAPKKK5 positively regulates plant height and yield in rice by affecting cell size, and that its underlying mechanism is based on increased endogenous GA content. Keywords: OstMAPKKK5, Plant height and yield, Cell size, Gibberellin, Oryza sativa

Abstract Background Noninvasive prenatal testing (NIPT) is commonly used to screen for fetal genetic abnormalities. However, the ability of NIPT to detect copy number variations (CNVs) has not been reported. Accordingly, in this study, we analyzed the efficiency of NIPT for the detection of fetal autosomal CNVs. Methods Patients who were positive for autosomal CNVs by NIPT and underwent diagnostic studies by karyotype analysis and chromosomal microarray (CMA) were evaluated. Samples were divided into groups according to age, in vitro fertilization, fetal‐free DNA concentration, uniquely mapped reads number, CNV size, and CNV type. Results Chromosomal microarray showed that the positive predictive value (PPV) of autosomal CNVs detected by NIPT was 14.89%. Increasing fetal DNA concentrations and uniquely mapped read numbers did not affect the PPV of CNVs detected by NIPT. There were no differences between microduplication and microdeletion PPVs detected by NIPT. The PPV of CNVs less than 10 Mb was significantly higher than that of CNVs greater than 10 Mb detected by NIPT. Conclusion The accuracy of NIPT for autosomal CNVs needs to be improved.

The effect of long noncoding RNAs (lncRNAs) on crop yield is unknown. Here, the authors show overexpression of a lncRNA, transcribed from the antisense strand of the previously discovered gene cluster LRK, can upregulate LRK genes’ expression, change histone modification status of LRK1, and increase rice grain yield.

The development of new signal systems for electrical biosensors could provide exciting new opportunities for biomedical analysis, pollutant monitoring, and explosive detection. The signal systems for commercial portable sensors involve the integration of a battery and a circuit conditioning system to power an amperometric biosensor. However, this increases the size and complexity of the entire system. In this study, we develop a simple amperometric biosensor that is directly powered by a button cell battery for the detection of lactate. A two-electrode sensing transducer was printed on cardboard or integrated on a ring. It was directly powered by a button cell battery, and connected to a multimeter for current measurement. This sensor showed a sensitive detection range of 0.04762-9.21429 mM and short measuring time of 2 min. These results show that this system can achieve an excellent sensing performance, and the construction of this new sensing system directly powered by a button cell battery offers a new method for further developing a wide range of miniaturized, flexible, portable, or wearable sensing systems, and these could be used in detecting various analytes that are important in medical diagnosis and environmental monitoring.

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.

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.

In four rice genomes, 85 ABC1-family genes were identified by comparative genomics, evolution, genetics, and physiology. One, OsABCl-13, was shown by knockdown and knockout experiments to affect plant height, grain size, and photosynthetic capability. [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]