Targeted inhibition of m6A demethylase FTO by FB23 attenuates allergic inflammation in the airway epithelium.

Epithelial cells play a crucial role in asthma, contributing to chronic inflammation and airway hyperresponsiveness. m6A modification, which involves key proteins such as the demethylase fat mass and obesity-associated protein (FTO), is crucial in the regulation of various diseases, including asthma. However, the role of FTO in epithelial cells and the development of asthma remains unclear. In this study, we investigated the demethylase activity of FTO using a small-molecule inhibitor FB23 in epithelial cells and allergic inflammation in vivo and in vitro. We examined the FTO-regulated transcriptome-wide m6A profiling by methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA-seq under FB23 treatment and allergic inflammation conditions. Immunofluorescence staining was performed to assess the tissue-specific expression of FTO in asthmatic bronchial mucosa. We demonstrated that FB23 alleviated allergic inflammation in IL-4/IL-13-treated epithelial cells and house dust mite (HDM)-induced allergic airway inflammation mouse model. The demethylase activity of FTO contributed to the regulation of TNF-α signaling via NF-κB and epithelial-mesenchymal transition-related pathways under allergic inflammation conditions in epithelial cells. FTO was expressed in epithelial, submucosal gland, and smooth muscle cells in human bronchial mucosa. In conclusion, FB23-induced inhibition of FTO alleviates allergic inflammation in epithelial cells and HDM-induced mice, potentially through diverse cellular processes and epithelial-mesenchymal transition signaling pathways, suggesting that FTO is a potential therapeutic target in asthma management.

Dynamic flyer in barrel imaging via high intensity short-pulse laser.

The thin flyer is a small-scale flying object, which is well known as the core functional element of the initiator. Understanding how flyers perform has been a long-standing issue in detonator science. However, it remains a significant challenge to explore how the flyer is formed and functions in the barrel of the initiator via tabletop devices. In this study, we present dynamic and unprecedented images of flyer in barrel via high intensity short-pulse laser. Advanced radiography, coupled with a high-intensity picosecond laser X-ray source, has enabled the provision of state-of-the-art radiographs in a single-shot experiment for observing micron-scale flyer formation in a hollow cylinder in nanoseconds. The flyer was clearly visible in the barrel and was accelerated and restricted differently from that without the barrel. This first implementation of a tabletop X-ray source provided a new approach for capturing dynamic photographs of small-scale flying objects, which were previously reported to be accessible only via an X-ray phase-contrast imaging system at the advanced photon source. These efforts have led to a significant improvement of radiographic capability and a greater understanding of the mechanisms of "burst" of exploding foil initiators for this application.

Photocatalysis Inhibits the Emergence of Multidrug-Resistant Bacteria in an Antibiotic-Resistant Bacterial Community in Aquatic Environments.

Bacterial antibiotic resistance has recently attracted increasing amounts of attention. Here, an artificially antibiotic-resistant bacterial community (ARBC) combined with five different constructed antibiotic-resistant bacteria (ARB) with single antibiotic resistance, namely, kanamycin (KAN), tetracycline (TET), cefotaxime (CTX), polymyxin B (PB), or gentamicin (GEM), was studied for the stress response to photocatalysis. With photocatalytic inactivation, the transfer and diffusion of antibiotic resistance genes (ARGs) in the ARBC decreased, and fewer multidrug-resistant bacteria (MDRB) emerged in aquatic environments. After several days of photocatalytic inactivation or Luria broth cultivation, >90% ARB were transformed to antibiotic-susceptible bacteria by discarding ARGs. Bacteria with double antibiotic resistance were the dominant species (99%) of residual ARB. The changes in ARG abundance varied, decreasing for the GEM and TET resistance genes and increasing for the KAN resistance genes. The change in the antibiotic resistance level was consistent with the change in ARG abundance. Correspondingly, point mutations occurred for the KAN, CTX and PB resistance genes after photocatalytic inactivation, which might be the reason why these genes persisted longer in the studied ARBC. In summary, photocatalytic inactivation could reduce the abundance of some ARGs and inhibit the emergence of MDRB as well as block ARG transfer in the bacterial community in aquatic environments. This work highlights the advantages of long-term photocatalytic inactivation for controlling antibiotic resistance and facilitates a better understanding of bacterial communities in real aquatic environments.

Blocking the TRAIL-DR5 Pathway Reduces Cardiac Ischemia-Reperfusion Injury by Decreasing Neutrophil Infiltration and Neutrophil Extracellular Traps Formation.

PURPOSE: Acute myocardial infarction (AMI) is a leading cause of mortality. Neutrophils penetrate injured heart tissue during AMI or ischemia-reperfusion (I/R) injury and produce inflammatory factors, chemokines, and extracellular traps that exacerbate heart injury. Inhibition of the TRAIL-DR5 pathway has been demonstrated to alleviate cardiac ischemia-reperfusion injury in a leukocyte-dependent manner. However, it remains unknown whether TRAIL-DR5 signaling is involved in regulating neutrophil extracellular traps (NETs) release. METHODS: This study used various models to examine the effects of activating the TRAIL-DR5 pathway with soluble mouse TRAIL protein and inhibiting the TRAIL-DR5 signaling pathway using DR5 knockout mice or mDR5-Fc fusion protein on NETs formation and cardiac injury. The models used included a co-culture model involving bone marrow-derived neutrophils and primary cardiomyocytes and a model of myocardial I/R in mice. RESULTS: NETs formation is suppressed by TRAIL-DR5 signaling pathway inhibition, which can lessen cardiac I/R injury. This intervention reduces the release of adhesion molecules and chemokines, resulting in decreased neutrophil infiltration and inhibiting NETs production by downregulating PAD4 in neutrophils. CONCLUSION: This work clarifies how the TRAIL-DR5 signaling pathway regulates the neutrophil response during myocardial I/R damage, thereby providing a scientific basis for therapeutic intervention targeting the TRAIL-DR5 signaling pathway in myocardial infarction.

Real-world effectiveness and predictors of super-responders to dupilumab in a Chinese uncontrolled asthma cohort.

Background: Dupilumab has been shown to be effective in clinical trials for moderate-to-severe uncontrolled asthma. However, the efficacy of dupilumab in the real world and the prediction of treatment response have not been well studied in patients with asthma. Objective: To investigate the efficacy of dupilumab and explore predictors of super-responders in a Chinese retrospective cohort. Methods: From January 2021 through December 2022, the patients with uncontrolled asthma who were treated with dupilumab for 4 months were included. Symptom control, type 2 inflammatory biomarkers, and lung function were collected at baseline and follow-up for efficacy assessment. Super-responders were defined as exacerbation-free, off maintenance of oral corticosteroids (mOCS), and with a score of the five-item Asthma Control Questionnaire (ACQ-5) of <0.5. The uni- and multivariable logistic regressions were used to construct predictive models for super-responders based on baseline features. Results: A total of 53 patients were included. After 4 months treatment, the median (interquartile range [IQR]) ACQ-5 score decreased from 1.8 (1.6-2.4) to 0.4 (0.2-0.8) (p < 0.001), the median (IQR) number of exacerbations, from 0.0 (0.0-1.0) to 0.0 (0.0-0.0) (p = 0.005). The median (IQR) dose of mOCS (prednisone equivalent) decreased from 15.0 mg/day (8.8-22.5 mg/day) to 2.5 mg/day (0.0-10.0 mg/day) (p = 0.008) in nine patients who were receiving mOCS. All efficacy assessment parameters, including sputum eosinophil were significantly improved, while blood eosinophil count did not decline (530 cells/mm³ [300-815 cells/mm³] versus 560 cells/mm³ [220-938 cells/mm³], p = 0.710). After taking dupilumab, 25 of 53 patients (47.2%) achieved a super-response. The age of onset < 42 years (odds ratio [OR] 7.471 [95% confidence interval {CI}, 1.286-43.394) and the baseline fractional exhaled nitric oxide (FeNO) of 25-50 ppb (OR 35.038 [95% CI, 3.104-395.553]) predicted super-responders, which showed a C-index of 0.822 (95% CI, 0.697-0.947). Conclusion: Dupilumab significantly improved symptom control, type 2 inflammatory markers, and lung function in Chinese patients with uncontrolled asthma. Airway eosinophils, rather than blood eosinophils, can be a reliable indicator of therapeutic efficacy. The early-onset asthma as well as the medium-high level of baseline FeNO contributed to the prediction of super-responders.

The Protection of Enzyme Activity for the Preparation of Humanized Polymerized Hemoglobin-Superoxide Dismutase-Catalase-Carbonic Anhydrase.

This work finds suitable enzyme activity protectants to improve the recovery rate of enzyme activity in the preparation of human polymerized hemoglobin-superoxide dismutase-catalase-carbonic anhydrase (PolyHb-SOD-CAT-CA), including trehalose, sucrose, glucose, hydroxypropyl-ß-cyclodextrin, and mannitol.Different types and concentrations of enzyme activity protective agents were added during polymerization to compare their protective ability to enzyme activity and the effect on the properties of hemoglobin. The study found that compared with trehalose, the protective effect of sucrose on CA enzyme activity is non-significant to that on hemoglobin, the recovery rate of SOD, and CAT enzyme activity has significant increased. Glucose, hydroxypropyl-ß-cyclodextrin, and mannitol are unsuitable for the added enzyme activity protective agent of PolyHb-SOD-CAT-CA.The protective effect of sucrose on CA was non-significant with trehalose. The protective effect of sucrose on SOD and CAT enzyme activity was higher than trehalose, and the protective effect reached the maximum when the concentration reached 1.5%.

Atmospheric VOCs in an industrial coking facility and the surrounding area: Characteristics, spatial distribution and source apportionment.

Industrial coking facilities are an important emission source for volatile organic compounds (VOCs). This study analyzed the atmospheric VOC characteristics within an industrial coking facility and its surrounding environment. Average concentrations of total VOCs (TVOCs) in the surrounding residential activity areas (R1 and R2), the coking facility (CF) and the control area (CA) were determined to be 138.5, 47.8, 550.0, and 15.0 µg/m3, respectively. The cold drum process and coking and quenching areas within the coking facility were identified as the main polluting processes. The spatial variation in VOCs composition was analyzed, showing that VOCs in the coking facility and surrounding areas were mainly dominated by aromatic compounds such as BTX (benzene, toluene, and xylenes) and naphthalene, with concentrations being negatively correlated with the distance from the coking facility (p < 0.01). The sources of VOCs in different functional areas across the monitoring area were analyzed, finding that coking emissions accounted for 73.5%, 33.3% and 27.7% of TVOCs in CF, R1 and R2, respectively. These results demonstrated that coking emissions had a significant impact on VOC concentrations in the areas surrounding coking facility. This study evaluates the spatial variation in exposure to VOCs, providing important information for the influence of VOCs concentration posed by coking facility to surrounding residents and the development of strategies for VOC abatement.

Scintillation of the orbital angular momentum of a Bessel Gaussian beam and its application on multi-parameter multiplexing.

The scintillation of the orbital angular momentum (OAM) of a Bessel Gaussian beam was derived based on the Rytov method to characterize the performance of the OAM communication. Moreover, a multi-parameter demultiplexing method was also proposed which could decode the OAM state, the amplitude and two additional beam width information dimensions. The advantages of the OAM states as the communication carrier over the beam intensity were that the minimum scintillation of the fundamental mode was smaller, and its corresponding radius also diverged slower. The coefficient of variation of the decoding amplitude was approximated to the square root of the radial minimum scintillation, and it provided an estimated decoding precision for the input sample selection. This study not only provided theoretical basis for communication link design, but also had a promising application on the large capacity beam multiplexing in free-space laser communication.

High-speed 4 × 4 silicon photonic plasma dispersive switch, operating at the 2†µm waveband.

The escalating need for expansive data bandwidth, and the resulting capacity constraints of the single mode fiber (SMF) have positioned the 2-µm waveband as a prospective window for emerging applications in optical communication. This has initiated an ecosystem of silicon photonic components in the region driven by CMOS compatibility, low cost, high efficiency and potential for large-scale integration. In this study, we demonstrate a plasma dispersive 4 × 4 photonic switch operating at the 2-µm waveband with the highest switching speed. The demonstrated switch operates across a 45-nm bandwidth, with 10-90% rise and 90-10% fall time of 1.78 ns and 3.02 ns respectively. In a 4 × 4 implementation, crosstalk below -15 dB and power consumption lower than 19.15 mW across all 16 optical paths are indicated. This result brings high-speed optical switching to the portfolio of devices at the promising waveband.

Polarization-multiplexed metasurface enabled tri-functional imaging.

Diffraction-limited focusing imaging, edge-enhanced imaging, and long depth of focus imaging offer crucial technical capabilities for applications such as biological microscopy and surface topography detection. To conveniently and quickly realize the microscopy imaging of different functions, the multifunctional integrated system of microscopy imaging has become an increasingly important research direction. However, conventional microscopes necessitate bulky optical components to switch between these functionalities, suffering from the system's complexity and unstability. Hence, solving the problem of integrating multiple functions within an optical system is a pressing need. In this work, we present an approach using a polarization-multiplexed tri-functional metasurface, capable of realizing the aforementioned imaging functions simply by changing the polarization state of the input and output light, enhancing the system structure's compactness and flexibility. This work offers a new avenue for multifunctional imaging, with potential applications in biomedicine and microscopy imaging.

Abrading-Induced Breakdown of Ag Nanoparticles into Atomically Dispersed Ag for Enhancing Antimicrobial Performance.

Silver is among the most essential antimicrobial agents. Increasing the efficacy of silver-based antimicrobial materials will reduce operating costs. Herein, we show that mechanical abrading causes atomization of Ag nanoparticles (AgNPs) into atomically dispersed Ag (AgSAs) on the surfaces of an oxide-mineral support, which eventually boosts the antibacterial efficacy considerably. This approach is straightforward, scalable, and applicable to a wide range of oxide-mineral supports; additionally, it does not require any chemical additives and operates under ambient conditions. The obtained AgSAs-loaded γ-Al2O3 inactivated Escherichia coli (E. coli) five times as fast as the original AgNPs-loaded γ-Al2O3. It can be utilized over 10 runs with minimal efficiency loss. The structural characterizations indicate that AgSAs exhibit a nominal charge of 0 and are anchored at the doubly bridging OH on the γ-Al2O3 surfaces. Mechanism studies demonstrate that AgSAs, like AgNPs, damage bacterial cell wall integrity, but they release Ag+ and superoxide substantially faster. This work not only provides a simple method for manufacturing AgSAs-based materials but also shows that AgSAs have better antibacterial properties than the AgNPs counterpart.

MASTR Pouch: Palm-size lab for point-of-care detection of Mpox using recombinase polymerase amplification and CRISPR technology.

Mpox (formerly referred as Monkeypox) outbreak has been declared a Public Health Emergency of International Concern. However, traditional polymerase chain reaction (PCR) diagnostic technology is not ideal for on-site applications. To conduct the sample-to-result Mpox viral particles detection outside the laboratories, we developed an easy-to-operate palm-size pouch, termed Mpox At-home Self-Test and point-of-caRe Pouch (MASTR Pouch). In this MASTR Pouch, the fast and accurate visualization was achieved by incorporating recombinase polymerase amplification (RPA) with clustered regularly interspaced short palindromic repeat (CRISPR)/Cas12a system. From viral particle lysis to naked eye readout, MASTR Pouch required only four simple steps to accomplish the analysis process within 35 min. Fifty-three Mpox pseudo-viral particles in exudate (10.6 particles/µL) were able to be detected. To verify the practicability, 104 mock Mpox clinical exudate specimens were tested. The clinical sensitivities were determined to be 91.7%- 95.8%. There was no false-positive result, validating the 100% clinical specificity. MASTR Pouch approaches the WHO's ASSURD criteria for point-of-care diagnostic, which will be beneficial for mitigating Mpox's global spread. The versatility potential of MASTR Pouch could further revolutionize infection diagnosis.

Novel Ag-bridged dual Z-scheme g-C3N4/BiOI/AgI plasmonic heterojunction: Exceptional photocatalytic activity towards tetracycline and the mechanism insight.

Rational design and synthesis of highly efficient and robust photocatalysts with positive exciton splitting and interfacial charge transfer for environmental applications is critical. Herein, aiming at overcoming the common shortcomings of traditional photocatalysts such as weak photoresponsivity, rapid combination of photo-generated carriers and unstable structure, a novel Ag-bridged dual Z-scheme g-C3N4/BiOI/AgI plasmonic heterojunction was successfully synthesized using a facile method. Results showed that Ag-AgI nanoparticles and three-dimensional (3D) BiOI microspheres were decorated highly uniformly on the 3D porous g-C3N4 nanosheet, resulting in a higher specific surface area and abundant active sites. The optimized 3D porous dual Z-scheme g-C3N4/BiOI/Ag-AgI manifested exceptional photocatalytic degradation efficiency of tetracycline (TC) in water with approximately 91.8% degradation efficiency within 165 min, outperforming majority of the reported g-C3N4-based photocatalysts. Moreover, g-C3N4/BiOI/Ag-AgI exhibited good stability in terms of activity and structure. In-depth radical scavenging and electron paramagnetic resonance (EPR) analyses confirmed the relative contributions of various scavengers. Mechanism analysis indicated that the improved photocatalytic performance and stability were ascribed to the highly ordered 3D porous framework, fast electron transfer of dual Z-scheme heterojunction, desirable photocatalytic performance of BiOI/AgI and synergistic effect of Ag plasmas. Therefore, the 3D porous Z-scheme g-C3N4/BiOI/Ag-AgI heterojunction had a good prospect for applications in water remediation. The current work provides new insight and useful guidance for designing novel structural photocatalysts for environment-related applications.

Optical frequency comb generation from a 1.65 µm single-section quantum well laser.

Optical frequency combs (OFCs) in the 1.65 µm wavelength band are promising for methane sensing and extended high-capacity optical communications. In this work, a frequency-modulated (FM) OFC is generated from a 1.65 µm single-section quantum well laser. This is characterized by a 1 kHz-wide beatnote signal at ∼19.4 GHz. Typical FM optical spectra are shown and optical linewidth of the OFC narrows through the mutual injection locking process in the comb formation. No distinct pulse train is observed on oscilloscope, which conforms with the FM operation. Furthermore, to add further evidence that four-wave mixing (FWM) is the driving mechanism of the comb formation, FWM frequency conversion characterization is conducted on a semiconductor optical amplifier (SOA) fabricated together with the tested laser. An efficiency of ∼-30 dB confirms the capability of FM mode locking.

[Practice of clinical application of noninvasive prenatal testing based on cell-free fetal DNA].

OBJECTIVE: To assess the application value of noninvasive prenatal testing (NIPT) based on cell-free fetal DNA. METHODS: The results of 2777 cases of basic and extended NIPT were retrospectively analyzed. The clinical data and outcome of pregnancy were analyzed, in addition with the diagnosis rate and testing efficiency. RESULTS: Among the 2777 pregnant women, 1192 (42.9%) had accepted basic NIPT and 1585 (57.1%) accepted extended NIPT. With a failure rate of 0.1%, 8 and 6 cases were reported respectively as high-risk pregnancies for trisomy 21 and sex chromosomal abnormalities. Other genetic abnormalities were detected in 32 cases. The positive predictive value for trisomy 21 was 85.7%, and one case of 47,XXX was diagnosed among 3 women with high risks for sex chromosomal abnormalities. For those with a high risk for other genetic abnormalities, pregnant diagnosis rates of basic and extended NIPT were 71.4% (5/7) and 68.2% (15/22), respectively. Seven copy number variations (CNVs) were confirmed, including one pathogenic CNV, one likely pathogenic CNV and 5 variants of unknown significance. Among 6 cases with high-risk of maternal CNVs, 5 fetuses and the mothers were confirmed to be carriers. No CNV was detected in the remainder fetus by chromosomal microarray analysis, while its mother was a carrier of the corresponding CNV. CONCLUSION: NIPT has shown a relatively high positive predictive value for the screening of trisomy 21 and maternal CNVs but with a limited efficiency for the discovery of fetal CNVs. For other genetic abnormalities signaled by NIPT, informed choice by the pregnant women during pre-testing consultation is recommended. Invasive prenatal diagnosis should be considered in the combination of NIPT reports and fetal ultrasound, while the residual risks should be fully informed.

Paternal Exposure to PM2.5 Programs Offspring's Energy Homeostasis.

Considerable studies show that maternal exposure to ambient fine particulate matter (PM2.5) programs offspring's susceptibility to obesity. However, few studies have investigated the effect of paternal PM2.5 exposure on offspring's energy homeostasis. This study thus tested whether paternal PM2.5 exposure programs offspring's energy homeostasis. Male C57Bl/6J mice were exposed to filtered air or concentrated ambient PM2.5 (CAP) for 12 weeks and then mated with normal female C57Bl/6J mice. The offspring were assessed for growth trajectories, food intakes, and body compositions, and the sperm miRNAs of those sires were profiled by microarray. Zygotic injection was used to test whether the miRNA identified by the microarray mediates the impact of paternal PM2.5 exposure on offspring's energy homeostasis. Paternal CAP exposure resulted in significant hypophagia and weight loss in male, but not female, offspring. The weight loss of male offspring was accompanied by decreases in the liver and kidney masses and paradoxically an increase in the adipose mass. Without further exposure to CAP, this programming was three-generationally transmitted along the paternal line. The sperm miRNA profiling revealed that mmu-mir6909-5p was the sole differentially expressed sperm miRNA due to PM2.5 exposure, and zygotic injection of mmu-mir6909-5p mimicked all the effects of paternal PM2.5 exposure on offspring's energy homeostasis. Paternal PM2.5 exposure programs offspring's energy homeostasis through increasing paternal sperm mmu-mir6909-5p.

Multidimensional Analyses Reveal Unequal Resource, Economic, and Environmental Gains and Losses among the Global Aluminum Trade Leaders.

Disputes around trade inequality have been growing over the last 2 decades, with different countries claiming inequality in different terms including monetary deficits, resource appropriation and degradation, and environmental emission transfer. Despite prior input-output-based studies analyzing multidimensional trade consequences at the sector level, there is a lack of bottom-up studies that uncover the complexity of trade imbalances at the product level. This paper quantifies four types of flows, monetary, resource, embodied energy use, and embodied greenhouse gas (GHG) emissions, resulting from aluminum trade for the four economies with the highest aluminum trade, that is, the United States, China, Japan, and Australia. Results show that the United States has a negative balance in monetary flows but a positive balance in resource flows, embodied energy use, and GHG emissions. China has a positive balance in monetary and resource flows but a negative balance in embodied energy use and GHG emissions. Japan has a positive balance in all flows, while Australia has a negative balance in all flows. These heterogeneous gains and losses along the global leaders of aluminum trade arise largely from their different trade structures and the heterogeneities of price, energy use, and GHG emission intensities of aluminum products; for example, Japan mainly imports unwrought aluminum, and its quantity is 3 times that of the exported semis and finished aluminum-containing products that have similar energy and GHG emission intensities but 20 times higher prices, while Australia mainly exports bauxite and alumina that have the lowest prices, the quantity of which is 25 times that of imported semis and finished products. This study suggests that resource-related trade inequalities are not uniform across economic and environmental impacts and that trade policies must be carefully considered from various dimensions.

Photocatalytic inactivation and destruction of harmful microalgae Karenia mikimotoi under visible-light irradiation: Insights into physiological response and toxicity assessment.

Harmful algal blooms (HABs) caused by Karenia mikimotoi have frequently happened in coastal waters worldwide, causing serious damages to marine ecosystems and economic losses. Photocatalysis has potential to in-situ inhibit algal growth using sustainable sunlight. However, the inactivation and detoxification mechanisms of microalgae in marine environment have not been systematically investigated. In this work, for the first time, visible-light-driven photocatalytic inactivation of K. mikimotoi was attempted using g-C3N4/TiO2 immobilized films as a model photocatalyst. The inactivation efficiency could reach 64% within 60 min, evaluated by real-time in vivo chlorophyll-a fluorometric method. The immobilized photocatalyst films also exhibited excellent photo-stability and recyclability. Mechanisms study indicated photo-generated h+ and 1O2 were the dominant reactive species. Algal cell rupture process was monitored by fluorescent microscope combined with SEM observation, which confirmed the damage of cell membrane followed by the leakage of the intracellular components including the entire cell nucleus. The physiological responses regarding up-regulation of antioxidant enzyme activity (i.e. CAT and SOD), intracellular ROSs level and lipid peroxidation were all observed. Moreover, the intracellular release profile and acute toxicity assessment indicated the toxic K. mikimotoi was successfully detoxified, and the released organic matter had no cytotoxicity. This work not only provides a potential new strategy for in-situ treatment of K. mikimotoi using sunlight at sea environments, but also creates avenue for understanding the inactivation and destruction mechanisms of marine microalgae treated by photocatalysis and the toxicity impacts on the marine environments.

[Analysis to the failure rate and causes of noninvasive prenatal testing based on high-throughput sequencing].

OBJECTIVE: To analyze the cause and pregnancy outcome for non-reportable cell-free DNA (cfDNA) results during non-invasive prenatal testing (NIPT). METHODS: cfDNA was extracted from maternal plasma from 5898 singleton pregnancies at 12 to 22 gestational weeks and underwent NIPT with strict quality control standards. For those with sub-standard results, redraw or invasive prenatal procedures were recommended. RESULTS: Among the 5898 cases, 32 have failed for the initial NIPT, including 17 cases with substandard cffDNA%, 10 cases with data fluctuation after twice library constructing and sequencing, and 5 cases with unidentifiable sex chromosome abnormalities. For these 32 cases, 2 directly underwent amniocentesis, and karyotyping analysis showed both were normal. Six of the 30 redrawn cases finally turned out to be nonreportable. The final nonreportable rate was therefore 0.1% (8/5898). Of the redrawn cases, 1 trisomy 21, 1 trisomy 18 and 1 trisomy 13 high risk-cases were identified, which were all confirmed to be false positive. Among the 6 nonreportable cases, 2 women underwent invasive prenatal testing, and 1 was found to have a normal fetal karyotype, while another was found to have an abnormal karyotype of mos45,X[32]/46,XY[18]. The other 4 nonreportable cases who did not accept invasive prenatal testing have all reported normal child development at follow-up. CONCLUSION: The main reason for nonreportable NIPT results was low cffDNA%. The high success rate of the redrawn cases has effectively increased the overall NIPT success rate and reduced the number of the cases necessitating invasive prenatal diagnosis. The initially nonreportable women may consider retesting after careful counseling with informed consent.

Sub-kHz linewidth, hybrid III-V/silicon wavelength-tunable laser diode operating at the application-rich 1647-1690†nm.

The wavelength region about of 1650 nm enables pervasive applications. Some instances include methane spectroscopy, free-space/fiber communications, LIDAR, gas sensing (i.e. C2H2, C2H4, C3H8), surgery and medical diagnostics. In this work, through the hybrid integration between an III-V optical amplifier and an extended, low-loss wavelength tunable silicon Vernier cavity, we report for the first time, a III-V/silicon hybrid wavelength-tunable laser covering the application-rich wavelength region of 1647-1690 nm. Room-temperature continuous wave operation is achieved with an output power of up to 31.1 mW, corresponding to a maximum side-mode suppression ratio of 46.01 dB. The laser is ultra-coherent, with an estimated linewidth of 0.7 kHz, characterized by integrating a 35 km-long recirculating fiber loop into the delayed self-heterodyne interferometer setup. The laser linewidth is amongst the lowest in hybrid/heterogeneous III-V/silicon lasers.