Genetic variations in the DYNC2H1 gene causing SRTD3 (short-rib thoracic dysplasia 3 with or without polydactyly)

Background and aims: Short-rib thoracic dysplasia 3 with or without polydactyly (SRTD3) represents a type of severe fetal skeletal dysplasia (SD) characterized by shortened limbs, narrow thorax with or without polydactyly, which is caused by the homozygous or compound heterozygous mutations in the DYNC2H1 gene. SRTD3 is a recessive disorder, identification of the responsible genetic variation would be beneficial to an accurate prenatal diagnosis and well-grounded counseling for the affected families.Material and methods: Two families having experienced recurrent fetal SDs were recruited and submitted to a multiplatform genetic investigation. Whole-exome sequencing (WES) was performed with samples collected from the probands. Sanger sequencing and fluorescent quantitative PCR (qPCR) were conducted as validation assays for suspected variations.Results: WES identified two compound heterozygous variations in the DYNC2H1(NM_001080463.2) gene, namely c.2386C>T (p.Arg796Trp) and c.7289T>C (p.Ile2430Thr) for one; and exon (64–83)del and c.8190G>T (p.Leu2730Phe) for the other, respectively. One variant in them, exon (64–83)del, was novelly identified.Conclusion: The study detected two compound heterozygous variation in DYNC2H1 including one novel deletion: exon (64–83) del. Our findings clarified the cause of fetal skeletal dysplasia in the subject families, provided guidance for their future pregnancies, and highlighted the value of WES in diagnosis of skeletal dysplasia with unclear prenatal indications

Microbicidal Phagocytosis of Nucleus Pulposus Cells Against Staphylococcus aureus via the TLR2/MAPKs Signaling Pathway

Intervertebral disc (IVD) is an immune-privileged organ that lacks immunocytes, such as macrophages or neutrophils; therefore, it is unclear how IVD immunological defense against bacterial infection occurs. Here, we demonstrated that nucleus pulposus cells (NPCs), the vital machinery for maintaining the homeostasis of IVD, exerted microbicidal activity against Staphylococcus aureus via induction of phagolysosome formation. Moreover, we found that the Toll-like receptor 2 (TLR2)/mitogen-activated protein kinases (MAPKs) signaling pathway is critical for bacterial phagocytosis and phagolysosome formation of NPCs. These findings demonstrated for the first time that NPCs could function as non-professional phagocytes against S. aureus infection, thereby enhancing antimicrobial defense against bacterial infections in IVDs

A High-Performance Mid-infrared Optical Switch Enabled by Bulk Dirac Fermions in Cd3As2

Pulsed lasers operating in the 2-5 {\mu}m band are important for a wide range of applications in sensing, spectroscopy, imaging and communications. Despite recent advances with mid-infrared gain media, the lack of a capable pulse generation mechanism, i.e. a passive optical switch, remains a significant technological challenge. Here we show that mid-infrared optical response of Dirac states in crystalline Cd3As2, a three-dimensional topological Dirac semimetal (TDS), constitutes an ideal ultrafast optical switching mechanism for the 2-5 {\mu}m range. Significantly, fundamental aspects of the photocarrier processes, such as relaxation time scales, are found to be flexibly controlled through element doping, a feature crucial for the development of convenient mid-infrared ultrafast sources. Although various exotic physical phenomena have been uncovered in three-dimensional TDS systems, our findings show for the first time that this emerging class of quantum materials can be harnessed to fill a long known gap in the field of photonics.Comment: 17 pages, 3 figure

Association between antibiotic use during early life and early-onset colorectal cancer risk overall and according to polygenic risk and FUT2 genotypes

Early-onset colorectal cancer (EOCRC) has been increasing worldwide. Potential risk factors may have occurred in childhood or adolescence. We investigated the associations between early-life factors and EOCRC risk, with a particular focus on long-term or recurrent antibiotic use (LRAU) and its interaction with genetic factors. Data on the UK Biobank participants recruited between 2006 and 2010 and followed up to February 2022 were used. We used logistic regression to estimate adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) of the associations between LRAU during early life and EOCRC risk overall and by polygenic risk score (constructed by 127 CRC-related genetic variants) and Fucosyltransferase 2 (FUT2), a gut microbiota regulatory gene. We also assessed the associations for early-onset colorectal adenomas, as precursor lesion of CRC, to examine the effect of LRAU during early-life and genetic factors on colorectal carcinogenesis. A total of 113 256 participants were included in the analysis, with 165 EOCRC cases and 719 EOCRA cases. LRAU was nominally associated with increased risk of early-onset CRC (OR = 1.48, 95% CI = 1.01-2.17, P = .046) and adenomas (OR = 1.40, 95% CI = 1.17-1.68, P < .001). When stratified by genetic polymorphisms of FUT2, LRAU appeared to confer a comparatively greater risk for early-onset adenomas among participants with rs281377 TT genotype (OR = 1.10, 95% CI = 0.79-1.52, P = .587, for CC genotype; OR = 1.75, 95% CI = 1.16-2.64, P = .008, for TT genotype; Pinteraction  = .089). Our study suggested that LRAU during early life is associated with increased risk of early-onset CRC and adenomas, and the association for adenomas is predominant among individuals with rs281377 TT/CT genotype. Further studies investigating how LRAU contributes together with genetic factors to modify EOCRC risk, particularly concerning the microbiome-related pathway underlying colorectal carcinogenesis, are warranted

The complete mitochondrial genome of Lutjanus ophuysenii and phylogenetic analysis

The complete mitochondrial genome of Lutjanus ophuysenii was analyzed by the next-generation sequencing. It was composed of 13 protein-coding genes (PCGs), 22 transfer RNA genes (tRNA), 2 ribosomal RNA genes (rRNA), and a control region with a total length of 16,498 bp. This mitochondrial genome has a base composition of 27.78% A, 16.55% G, 30.68% C, and 24.98% T. The phylogenetic analysis revealed that the L. ophuysenii has the closest relationship with L. votta. This mitochondrial genome provides important information for the phylogenetic relationship and genetic resource in this species

Advanced backstepping control based on ADR for non-affine non-strict feedback nonlinear systems

Few results are made on non-affine non-strict feedback nonlinear systems, which is a challenging problem in the control theory. In this paper, a novel control method based on an advanced backstepping and auto disturbance rejection is presented for a class of non-affine non-strict nonlinear feedback systems. The proposed advanced backstepping controller consists of differentiator and extended state observer, which are respectively used to approach the derivative of the virtual control and estimate the unknown part of the system. The framework of the proposed controller is both systematic and simple, and the assumptions have been relaxed. Moreover, the input to state stability analysis shows that the system states can asymptotically converge to an arbitrarily small region of equilibrium point. The simulation studies proved the effectiveness of the proposed design scheme

The complete mitochondrial genome of Heteropriacanthus cruentatus and implication of phylogenetic status

The complete mitochondrial genome of Heteropriacanthus cruentatus has been obtained and annotated through Illumina next-generation sequencing. This mitogenome was found to be 16,506 bp in length, containing 13 protein-coding genes (PCGs), 22 transfer RNA genes (tRNA), and 2 ribosomal RNA genes (rRNA). This overall base composition of the complete mitogenome for this species included 27.52% A, 24.46% T, 16.99% G and 31.04% C. The phylogenetic analysis revealed that the H. cruentatus has the closest relationship with Pristigenys niphonia. This study provides an important resource for reviewing the phylogenetic relationships and taxonomic status of this species

An Energy-Efficient Underground Localization System Based on Heterogeneous Wireless Networks

A precision positioning system with energy efficiency is of great necessity for guaranteeing personnel safety in underground mines. The location information of the miners’ should be transmitted to the control center timely and reliably; therefore, a heterogeneous network with the backbone based on high speed Industrial Ethernet is deployed. Since the mobile wireless nodes are working in an irregular tunnel, a specific wireless propagation model cannot fit all situations. In this paper, an underground localization system is designed to enable the adaptation to kinds of harsh tunnel environments, but also to reduce the energy consumption and thus prolong the lifetime of the network. Three key techniques are developed and implemented to improve the system performance, including a step counting algorithm with accelerometers, a power control algorithm and an adaptive packets scheduling scheme. The simulation study and experimental results show the effectiveness of the proposed algorithms and the implementation

Optimal Power Allocation for a Relaying-Based Cognitive Radio Network in a Smart Grid

This paper obtains optimal power allocation to the data aggregator units (DAUs) and relays for cognitive wireless networks in a smart grid (SG). Firstly, the mutual interference between the primary user and the DAU are considered, and the expressions of the DAU transmission signal are derived based on the sensing information. Secondly, we use the particle swarm optimization (PSO) algorithm to search for the optimal power allocation to minimize the costs to the utility company. Finally, the impact of the sensing information on the network performance is studied. Then two special cases (namely, that only one relay is selected, and that the channel is not occupied by the primary user) are discussed. Simulation results demonstrate that the optimal power allocation and the sensing information of the relays can reduce the costs to the utility company for cognitive wireless networks in a smart grid