Distinctive Lipid Characteristics of Colorectal Cancer Revealed through Non-targeted Lipidomics Analysis of Tongue Coating.

The metabolites and microbiota in tongue coating display distinct characteristics in certain digestive disorders, yet their relationship with colorectal cancer (CRC) remains unexplored. Here, we employed liquid chromatography coupled with tandem mass spectrometry to analyze the lipid composition of tongue coating using a nontargeted approach in 30 individuals with colorectal adenomas (CRA), 32 with CRC, and 30 healthy controls (HC). We identified 21 tongue coating lipids that effectively distinguished CRC from HC (AUC = 0.89), and 9 lipids that differentiated CRC from CRA (AUC = 0.9). Furthermore, we observed significant alterations in the tongue coating lipid composition in the CRC group compared to HC/CRA groups. As the adenoma-cancer sequence progressed, there was an increase in long-chain unsaturated triglycerides (TG) levels and a decrease in phosphatidylethanolamine plasmalogen (PE-P) levels. Furthermore, we noted a positive correlation between N-acyl ornithine (NAOrn), sphingomyelin (SM), and ceramide phosphoethanolamine (PE-Cer), potentially produced by members of the Bacteroidetes phylum. The levels of inflammatory lipid metabolite 12-HETE showed a decreasing trend with colorectal tumor progression, indicating the potential involvement of tongue coating microbiota and tumor immune regulation in early CRC development. Our findings highlight the potential utility of tongue coating lipid analysis as a noninvasive tool for CRC diagnosis.

Genome-wide association study identifies novel susceptible loci and evaluation of polygenic risk score for chronic obstructive pulmonary disease in a Taiwanese population.

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) describes a group of progressive lung diseases causing breathing difficulties. While COPD development typically involves a complex interplay between genetic and environmental factors, genetics play a role in disease susceptibility. This study used genome-wide association studies (GWAS) and polygenic risk score (PRS) to elucidate the genetic basis for COPD in Taiwanese patients. RESULTS: GWAS was performed on a Taiwanese COPD case-control cohort with a sample size of 5,442 cases and 17,681 controls. Additionally, the PRS was calculated and assessed in our target groups. GWAS results indicate that although there were no single nucleotide polymorphisms (SNPs) of genome-wide significance, prominent COPD susceptibility loci on or nearby genes such as WWTR1, EXT1, INTU, MAP3K7CL, MAMDC2, BZW1/CLK1, LINC01197, LINC01894, and CFAP95 (C9orf135) were identified, which had not been reported in previous studies. Thirteen susceptibility loci, such as CHRNA4, AFAP1, and DTWD1, previously reported in other populations were replicated and confirmed to be associated with COPD in Taiwanese populations. The PRS was determined in the target groups using the summary statistics from our base group, yielding an effective association with COPD (odds ratio [OR] 1.09, 95% confidence interval [CI] 1.02-1.17, p = 0.011). Furthermore, replication a previous lung function trait PRS model in our target group, showed a significant association of COPD susceptibility with PRS of Forced Expiratory Volume in one second (FEV1)/Forced Vital Capacity (FCV) (OR 0.89, 95% CI 0.83-0.95, p = 0.001). CONCLUSIONS: Novel COPD-related genes were identified in the studied Taiwanese population. The PRS model, based on COPD or lung function traits, enables disease risk estimation and enhances prediction before suffering. These results offer new perspectives on the genetics of COPD and serve as a basis for future research.

Chromatin lysine acylation: On the path to chromatin homeostasis and genome integrity.

The fundamental role of cells in safeguarding the genome's integrity against DNA double-strand breaks (DSBs) is crucial for maintaining chromatin homeostasis and the overall genomic stability. Aberrant responses to DNA damage, known as DNA damage responses (DDRs), can result in genomic instability and contribute significantly to tumorigenesis. Unraveling the intricate mechanisms underlying DDRs following severe damage holds the key to identify therapeutic targets for cancer. Chromatin lysine acylation, encompassing diverse modifications such as acetylation, lactylation, crotonylation, succinylation, malonylation, glutarylation, propionylation, and butyrylation, has been extensively studied in the context of DDRs and chromatin homeostasis. Here, we delve into the modifying enzymes and the pivotal roles of lysine acylation and their crosstalk in maintaining chromatin homeostasis and genome integrity in response to DDRs. Moreover, we offer a comprehensive perspective and overview of the latest insights, driven primarily by chromatin acylation modification and associated regulators.

Ultralow-Energy-Consumption Photosynaptic Transistor Utilizing Conjugated Polymers/Perovskite Quantum Dots Nanocomposites With Ligand Density Optimization.

The photosynaptic transistor stands as a promising contender for overcoming the von Neumann bottleneck in the realm of photo-communication. In this context, photonic synaptic transistors is developed through a straightforward solution process, employing an organic semiconducting polymer with pendant-naphthalene-containing side chains (PDPPNA) in combination with ligand-density-engineered CsPbBr3 perovskite quantum dots (PQDs). This fabrication approach allows the devices to emulate fundamental synaptic behaviors, encompassing excitatory postsynaptic current, paired-pulse facilitation, the transition from short-to-long-term memory, and the concept of "learning experience." Notably, the phototransistor, incorporating the blend of the PDPPNA and CsPbBr3 PQDs washed with ethyl acetate, achieved an exceptional memory ratio of 104. Simultaneously, the same device exhibited an impressive paired-pulse facilitation ratio of 223% at a moderate operating voltage of -4 V and an extraordinarily low energy consumption of 0.215 aJ at an ultralow operating voltage of -0.1 mV. Consequently, these low-voltage synaptic devices, constructed with a pendant side-chain engineering of organic semiconductors and a ligand density engineering of PQDs through a simple fabrication process, exhibit substantial potential for replicating the visual memory capabilities of the human brain.

A Functionally Asymmetric Janus Hygro-Photothermal Hybrid for Atmospheric Water Harvesting in Arid Regions.

Metal-organic frameworks (MOFs) are high-performance adsorbents for atmospheric water harvesting but have poor water-desorption ability, requiring excess energy input to release the trapped water. Addressing this issue, a Janus-structured adsorbent with functional asymmetry is presented. The material exhibits contrasting functionalities on either face - a hygroscopic face interfaced with a photothermal face. Hygroscopic aluminum fumarate MOF and photothermal CuxS layers are in-situ grown on opposite sides of a Cu/Al bimetallic substrate, resulting in a CuxS-Cu/Al-MOF Janus hygro-photothermal hybrid. The two faces serve as independent "factories" for photothermal conversion and water adsorption-desorption respectively, while the interfacing bimetallic layer serves as a "heat conveyor belt" between them. Due to the high porosity and hydrophilicity of the MOF, the hybrid exhibits a water-adsorption capacity of 0.161 g g-1 and a fast adsorption rate (saturation within 52 min) at 30% relative humidity. Thanks to the photothermal CuxS, the hybrid can reach 71.5 °C under 1 Sun in 20 min and desorb 97% adsorbed water in 40 min, exhibiting a high photothermal conversion efficiency of over 90%. CuxS-Cu/Al-MOF exhibits minimal fluctuations after 200 cycles, and its water-generation capacity is 3.21 times that of powdery MOF in 3 h in a self-designed prototype in one cycle.

Dual-Coating of Fluorinated Polydimethylsiloxane/Fluorinated SiO2 Nanoparticles for Superhydrophobic and High-Efficiency Bacteriostatic Surface.

A simple two-step spray method is used to prepare superhydrophobic and bacteriostatic surfaces, involving dual-coating with polydimethylsiloxane-normal-fluorine (PDMS-NF) or branched-fluorine (PDMS-BF) in combination with fluorinated silica nanoparticles (FSiO2 -NPs) using a spray technique. This approach has the potential to create surfaces with both water-repellent and antimicrobial properties, which could be useful in a variety of applications. It is noteworthy that the dual-coating on cotton fabric exhibited an impressive dual-scale roughness and achieved superhydrophobicity with a water contact angle of 158° and a hysteresis of less than 3°. Additionally, the coating was subjected to an ultra-high concentration of bacteria (109 CFU/mL) and was still able to inhibit more than 80 % of attachment, demonstrating its effectiveness as a bacteriostatic surface.

Inserting colloidal quantum dots into GaN mesa-array subsurface porous structures through electrochemical etching for display color conversion application.

High-efficiency photon color conversion is an approach of great potential for implementing color display. Inspired by the observation of emission enhancement in a nanoscale cavity, a novel technique to fabricate an array of color converter by mixing colloidal quantum dots (QDs) with the electrolyte of an electrochemical etching (ECE) process is demonstrated. In this process, QDs flow with the electrolyte into the etched subsurface nanoscale porous structure (PS) and settle inside. Since the PS formation and hence QD insertion are controlled by the flow path of the applied electric current in the ECE process, this technique can be used for fabricating any graphic pattern. The nanostructure of such a QD-inserted mesa is examined to confirm QD insertion. Although only single-color mesa arrays are demonstrated in this paper, this technique can be used for fabricating a multiple-color mesa array if a QD or a light-emitting nanoparticle of higher thermal stability is available.

Rate of graft retear is higher in over-the-top superior capsular reconstruction for massive posterosuperior rotator cuff tears with subscapularis tear.

PURPOSE: To compare side-to-side superior capsular reconstruction (SCR) with over-the-top SCR in terms of functional outcomes, pain relief and allograft survival rates. METHODS: Patients who had undergone arthroscopic dermal allograft SCR for massive irreparable rotator cuff tears and clinical follow-up for ≥2 years were recruited. All patients underwent postoperative assessment with routine radiographic analysis for acromiohumeral distances, ultrasound imaging 1 and 3 months after SCR and magnetic resonance imaging (MRI) at least 12 months after SCR. The outcome measures were visual analogue scale (VAS), American Shoulder and Elbow Surgeons (ASES), Constant and Single Assessment Numeric Evaluation (SANE) scores. RESULTS: SCR was performed in 56 patients including side-to-side SCR in 32 and over-the-top SCR in 24. Postoperative MRI showed that the grafts were intact in 46 patients (82.1%; 26 who underwent side-to-side SCR and 20 who underwent over-the-top SCR). The proportion of nonhealing grafts in the over-the-top group was significantly higher with concomitant subscapularis tears (60% vs. 5.3%; p = 0.02). VAS scores and functional outcomes improved postoperatively in both groups and postoperative VAS (1.4 vs. 1.7; n.s.), Constant (74.8 vs. 76.0; n.s.), mean ASES (87.4 vs. 89.1; n.s.) and mean SANE (81.7 vs. 84.3; n.s.) scores did not differ significantly. CONCLUSION: For massive rotator cuff tears, over-the-top and side-to-side SCR achieve similar pain relief and functional improvement, and the rate of healing allografts is high. However, over-the-top SCR is not recommended for massive posterosuperior rotator cuff tears with repairable subscapularis tendon tears due to a higher nonhealing rate. LEVEL OF EVIDENCE: Level III.

Design and Implementation of an Intensive Care Unit Command Center for Medical Data Fusion.

The rapid advancements in Artificial Intelligence of Things (AIoT) are pivotal for the healthcare sector, especially as the world approaches an aging society which will be reached by 2050. This paper presents an innovative AIoT-enabled data fusion system implemented at the CMUH Respiratory Intensive Care Unit (RICU) to address the high incidence of medical errors in ICUs, which are among the top three causes of mortality in healthcare facilities. ICU patients are particularly vulnerable to medical errors due to the complexity of their conditions and the critical nature of their care. We introduce a four-layer AIoT architecture designed to manage and deliver both real-time and non-real-time medical data within the CMUH-RICU. Our system demonstrates the capability to handle 22 TB of medical data annually with an average delay of 1.72 ms and a bandwidth of 65.66 Mbps. Additionally, we ensure the uninterrupted operation of the CMUH-RICU with a three-node streaming cluster (called Kafka), provided a failed node is repaired within 9 h, assuming a one-year node lifespan. A case study is presented where the AI application of acute respiratory distress syndrome (ARDS), leveraging our AIoT data fusion approach, significantly improved the medical diagnosis rate from 52.2% to 93.3% and reduced mortality from 56.5% to 39.5%. The results underscore the potential of AIoT in enhancing patient outcomes and operational efficiency in the ICU setting.

X-linked BCOR variants identified in Chinese Han patients with congenital heart disease.

BACKGROUND: Congenital heart disease (CHD) frequently manifests as a complex phenotype and approximately one-third of cases may be caused by genetic factors. BCOR, an X-linked gene encoding the corepressor of BCL6, has been demonstrated to be closely involved in human heart development. However, whether BCOR variants represent the genetic etiology underlying CHD needs further investigation. METHODS: We performed whole exome sequencing on CHD nuclear families and identified a candidate gene, BCOR, by robust bioinformatic analysis and medical literature searches. Targeted DNA sequencing of the candidate gene was conducted and then the association between variants and the risk of developing CHD was analyzed. The effects of BCOR mutations on gene expression, localization, protein interaction, and signaling pathways were evaluated in vitro. RESULTS: We identified a BCOR hemizygous missense variant (c.1448C>T, p.Pro483Leu) in a male proband presented with CHD/heterotaxy. Sanger sequencing confirmed that this variant was inherited from his asymptomatic mother. Interestingly, through literature searches, we observed another novel BCOR hemizygous missense variant (c.1619G>A, p.Arg540Gln) in a CHD patient with heterotaxy, supporting the pathogenic evidence of BCOR variants. Functional experiments conducted in vitro revealed that the variant p.Pro483Leu altered the subcellular localization of BCOR protein, disrupted its interaction with BCL6, and significantly promoted cell proliferation, whereas the variant p.Arg540Gln displayed no obvious effects. Nevertheless, transcriptional analysis revealed that down-regulation of BCOR substantially enhanced the activities of mitogen-activated protein and phosphoinositide 3-kinase-AKT signaling pathways, which are closely attributed to heart development. Targeted sequencing of 932 sporadic CHD patients enriched nine variants of BCOR predicted as likely rare and damaging and a septal defect was present in 81.8% (9/11) of them, including the two probands, which was consistent with the possible phenotype caused by BCOR defects. CONCLUSIONS: The findings of the present study indicate that variants in BCOR may predispose individuals to CHD in the Chinese Han population.

Bimetallic MOF-Derived Solar-Triggered Monolithic Adsorbent for Enhanced Atmospheric Water Harvesting.

The development of economical, energy-saving, and efficient metal-organic framework (MOF)-based adsorbents for atmospheric water collection is highly imperative for the rapid advancement of renewable freshwater resource exploitation. Herein, a feasible one-step solvothermal formation strategy of bimetallic MOF (BMOF) is proposed and applied to construct a solar-triggered monolithic adsorbent for enhanced atmospheric water collection. Benefiting from the reorganization and adjustment of topology structure by Al atoms and Fe atoms, the resultant BMOF(3) consisting of Al-fumarate and MIL-88A has a higher specific surface area (1202.99 m2  g-1 ) and pore volume (0.51 cm3  g-1 ), thereby outperforming the parental MOFs and other potential MOFs in absorbing water. Expanding upon this finding, the solar-triggered monolithic adsorbent is further developed through a bottom-up assembly of polyaniline/chitosan layers and hybridized BMOF(3) skeletons on a glass fiber support. The resultant monolithic adsorbent exhibits superior sorption-desorption kinetics, leading to directional water transport and rapid solar-assisted vapor diffusion. As a proof-of-concept demonstration, an exquisite water harvester is constructed to emphasize a high water yield of 1.19 g g-1 per day of the designed monolithic adsorbent. Therefore, the design and validation of bimetallic MOF-derived solar-triggered adsorbent in this work are expected to provide a reference for the large-scale applications of MOF-based atmospheric water harvesting.

Perovskite-Nanocrystal-Doped Cellulose Nanocrystal Ligands for Electrospun Nanofibers with Excellent Stability.

Because of their exceptional physical and thermal properties, cellulose nanocrystals (CNCs) are a highly promising bio-based material for reinforcing fillers. Studies have revealed that some functional groups from CNCs can be used as a capping ligand to coordinate with metal nanoparticles or semiconductor quantum dots during the fabrication of novel complex materials. Therefore, through CNCs ligand encapsulation and electrospinning, perovskite-NC-embedded nanofibers with exceptional optical and thermal stability are demonstrated. The results indicate that, after continuous irradiation or heat cycling, the relative photoluminescence (PL) emission intensity of the CNCs-capped perovskite-NC-embedded nanofibers is maintained at ≈90%. However, the relative PL emission intensity of both ligand-free and long-alkyl-ligand-doped perovskite-NC-embedded nanofibers decrease to almost 0%. These results are attributable to the formation of specific clusters of perovskite NCs along with the CNCs structure and thermal property improvement of polymers. CNCs-doped luminous complex materials offer a promising avenue for stability-demanding optoelectronic devices and other novel optical applications.

Reproduction of mode-locked pulses by spectrotemporal domain-informed deep learning.

The accurate reproduction of unique pulse states in a mode-locked fiber laser is an important scientific issue and has wide applications in the laser industry. We present what we believe to be a novel method for automatically and precisely reproducing targeted soliton states in a mode-locked fiber laser by spectrotemporal domain-informed deep learning. Targeted solitons are experimentally reproduced via a superior matching process with a spectrotemporal mean square error (MSE) of 3.99 × 10-5. The outstanding feature of our reproduction algorithm is that the pulse information in both the spectral and temporal domains is jointly adopted for reconstructing targeted soliton states from white noise, rather than establishing arbitrary mode-locked pulse states, as described in previous studies. Additionally, a single-layer perceptron model is proposed to retrieve the phase distribution of a mode-locked pulse, validating the physical completeness of our reproduction approach. Our approach advances ultrafast laser technology, enabling the precise control of pulse dynamics in applications such as optical communication and nonlinear optics.

Photon color conversion enhancement of colloidal quantum dots inserted into a subsurface laterally-extended GaN nano-porous structure in an InGaN/GaN quantum-well template.

To improve the color conversion performance, we study the nanoscale-cavity effects on the emission efficiency of a colloidal quantum dot (QD) and the Förster resonance energy transfer (FRET) from quantum well (QW) into QD in a GaN porous structure (PS). For this study, we insert green-emitting QD (GQD) and red-emitting QD (RQD) into the fabricated PSs in a GaN template and a blue-emitting QW template, and investigate the behaviors of the photoluminescence (PL) decay times and the intensity ratios of blue, green, and red lights. In the PS samples fabricated on the GaN template, we observe the efficiency enhancements of QD emission and the FRET from GQD into RQD, when compared with the samples of surface QDs, which is attributed to the nanoscale-cavity effect. In the PS samples fabricated on the QW template, the FRET from QW into QD is also enhanced. The enhanced FRET and QD emission efficiencies in a PS result in an improved color conversion performance. Because of the anisotropic PS in the sample surface plane, the polarization dependencies of QD emission and FRET are observed.

Surface plasmon coupling effects on the photon color conversion behaviors of colloidal quantum dots in a GaN nanoscale hole with a nearby quantum-well structure.

To improve color conversion performance for color display application, we study the near-field-induced nanoscale-cavity effects on the emission efficiency and Förster resonance energy transfer (FRET) under the condition of surface plasmon (SP) coupling by inserting colloidal quantum dots (QDs) and synthesized Ag nanoparticles (NPs) into surface nano-holes fabricated on a GaN template and an InGaN/GaN quantum-well (QW) template. In the QW template, the inserted Ag NPs are close to either QWs or QDs for producing three-body SP coupling to enhance color conversion. Time-resolved and continuous-wave photoluminescence (PL) behaviors of the QW- and QD-emitting lights are investigated. The comparison between the nano-hole samples and the reference samples of surface QD/Ag NP shows that the nanoscale-cavity effect of the nano-hole leads to the enhancements of QD emission, FRET between QDs, and FRET from QW into QD. The SP coupling induced by the inserted Ag NPs can enhance the QD emission and FRET from QW into QD. Its result is further enhanced through the nanoscale-cavity effect. The relative continuous-wave PL intensities among different color components also show the similar behaviors. By introducing SP coupling to a color conversion device with the FRET process in a nanoscale cavity structure, we can significantly improve the color conversion efficiency. Simulation results confirm the basic observations in experiment.

Chiral photonic topological states in Penrose quasicrystals.

Electromagnetic topological edge states typically are created in photonic systems with crystalline symmetry and these states emerge because of the topological feature of bulk Bloch bands in momentum space according to the bulk-edge correspondence principle. In this work, we demonstrate the existence of chiral topological electromagnetic edge states in Penrose-tiled photonic quasicrystals made of magneto-optical materials, without relying on the concept of bulk Bloch bands in momentum space. Despite the absence of bulk Bloch bands, which naturally defiles the conventional definition of topological invariants in momentum space characterizing these states, such as the Chern number, we show that some bandgaps in these photonic quasicrystals still could host unidirectional topological electromagnetic edge states immune to backscattering in both cylinders-in-air and holes-in-slab configurations. Employing a real-space topological invariant based on the Bott index, our calculations reveal that the bandgaps hosting these chiral topological edge states possess a nontrivial Bott index of ±1, depending on the direction of the external magnetic field. Our work opens the door to the study of topological states in photonic quasicrystals.

65,536-ary orbital angular momentum-shift keying free-space optical communication based on few-shot learning.

In an orbital angular momentum-shift keying free-space optical (OAM-SK FSO) communication system, precisely recognizing OAM superposed modes at the receiver site is crucial to improve the communication capacity. While deep learning (DL) provides an effective method for OAM demodulation, with the increase of OAM modes, the dimension explosion of OAM superstates results in unacceptable costs on training the DL model. Here, we demonstrate a few-shot-learning-based demodulator to achieve a 65,536-ary OAM-SK FSO communication system. By learning from only 256 classes of samples, the remaining 65,280 unseen classes can be predicted with an accuracy of more than 94%, which saves a large number of resources on data preparation and model training. Based on this demodulator, we first realize the single transmission of a color pixel and the single transmission of two gray scale pixels on the application of colorful-image-transmission in free space with an average error rate less than 0.023%. This work may provide a new, to the best of our knowledge, approach for big data capacity in optical communication systems.

Organic-Inorganic Phenolic/POSS Hybrids Provide Highly Ordered Mesoporous Structures Templated by High Thermal Stability of PS-b-P4VP Diblock Copolymer.

Anionic living polymerization was used to prepare a diblock copolymer of poly(styrene-b-4-vinyl pyridine) (PS-b-P4VP), and a phenolic resin with a double-decker silsesquioxane (DDSQ) cage structure was used to form a phenolic/DDSQ hybrid (PDDSQ-30 with 30 wt.% DDSQ). Strong intermolecular hydrogen bonding could be confirmed through the hydroxyl (OH) groups of PDDSQ hybrid with the pyridine group of the P4VP block in PDDSQ-30/PS-b-P4VP blends based on Fourier transform infrared spectroscopy analyses, where increasing PDDSQ concentrations resulted in a higher proportion of hydrogen-bonded pyridine groups. After thermal polymerization at 180 °C, the self-assembled structures of these PDDSQ/PS-b-P4VP blends were revealed by data from small-angle X-ray scattering (SAXS) and transmission electron microscopy (TEM), where the d-spacing increased with raising PDDSQ concentration. Because relatively higher thermal stability of the PDDSQ hybrid than pure phenolic resin and PS-b-P4VP template, we can obtain the long ranger order of mesoporous PDDSQ hybrids after removing the PS-b-P4VP template, which reveals the high surface area and high pore volume with cylindrical and spherical structures corresponding to the PDDSQ compositions that are rarely observed by using pure phenolic resin as the matrix and could be used in supercapacitor application.

Biallelic mutations of TTC12 and TTC21B were identified in Chinese patients with multisystem ciliopathy syndromes.

BACKGROUND: Abnormalities in cilia ultrastructure and function lead to a range of human phenotypes termed ciliopathies. Many tetratricopeptide repeat domain (TTC) family members have been reported to play critical roles in cilium organization and function. RESULTS: Here, we describe five unrelated family trios with multisystem ciliopathy syndromes, including situs abnormality, complex congenital heart disease, nephronophthisis or neonatal cholestasis. Through whole-exome sequencing and Sanger sequencing confirmation, we identified compound heterozygous mutations of TTC12 and TTC21B in six affected individuals of Chinese origin. These nonsynonymous mutations affected highly conserved residues and were consistently predicted to be pathogenic. Furthermore, ex vivo cDNA amplification demonstrated that homozygous c.1464 + 2 T > C of TTC12 would cause a whole exon 16 skipping. Both mRNA and protein levels of TTC12 were significantly downregulated in the cells derived from the patient carrying TTC12 mutation c.1464 + 2 T > C by real-time qPCR and immunofluorescence assays when compared with two healthy controls. Transmission electron microscopy analysis further identified ultrastructural defects of the inner dynein arms in this patient. Finally, the effect of TTC12 deficiency on cardiac LR patterning was recapitulated by employing a morpholino-mediated knockdown of ttc12 in zebrafish. CONCLUSIONS: To the best of our knowledge, this is the first study reporting the association between TTC12 variants and ciliopathies in a Chinese population. In addition to nephronophthisis and laterality defects, our findings demonstrated that TTC21B should also be considered a candidate gene for biliary ciliopathy, such as TTC26, which further expands the phenotypic spectrum of TTC21B deficiency in humans.

Copy number variant analysis for syndromic congenital heart disease in the Chinese population.

BACKGROUND: Syndromic congenital heart disease (CHD) is among the most severe conditions in the pediatric population. Copy number variant (CNV) is an important cause of syndromic CHD, but few studies focused on CNVs related to these patients in China. The present study aimed to identify pathogenic CNVs associated with syndromic CHD in the Chinese population. METHODS: A total of 109 sporadic patients with syndromic CHD were applied chromosomal microarray analysis (CMA). Phenotype spectrum of pathogenic or likely pathogenic CNVs was analyzed. CHD-related genes were prioritized from genes within pathogenic or likely pathogenic CNVs by VarElect, OVA, AMELIE, and ToppGene. RESULTS: Using CMA, we identified 43 candidate CNVs in 37/109 patients. After filtering CNVs present in the general population, 29 pathogenic/likely pathogenic CNVs in 24 patients were identified. The diagnostic yield of CMA for pathogenic/likely pathogenic CNVs was 23.1% (24/104), excluding 5 cases with aneuploidies or gross chromosomal aberrations. The overlapping analysis of CHD-related gene lists from different prioritization tools highlighted 16 CHD candidate genes. CONCLUSION: As the first study focused on CNVs in syndromic CHD from the Chinese population, this study reveals the importance of CMA in exploring the genetic etiology of syndromic CHD and expands our understanding of these complex diseases. The bioinformatic analysis of candidate genes suggests several CHD-related genes for further functional research.