Diagnosis of mixed infection and a primary immunodeficiency disease using next-generation sequencing: a case report

Major Histocompatibility Complex Class II (MHC II) deficiency is a rare primary immunodeficiency disorder (PID) with autosomal recessive inheritance pattern. The outcome is almost fatal owing to delayed diagnosis and lacking of effective therapy. Therefore, prompt diagnosis, timely and effective treatment are critical. Here, we report a 117-day-old boy with diarrhea, cough, cyanosis and tachypnea who was failed to be cured by empiric antimicrobial therapy initially and progressed to severe pneumonia and respiratory failure. The patient was admitted to the pediatric intensive care unit (PICU) immediately and underwent a series of tests. Blood examination revealed elevated levels of inflammatory markers and cytomegalovirus DNA. Imaging findings showed signs of severe infection of lungs. Finally, the diagnosis was obtained mainly through next-generation sequencing (NGS). We found out what pathogenic microorganism he was infected via repeated conventional detection methods and metagenomic next-generation sequencing (mNGS) of sputum and bronchoalveolar lavage fluid (BALF). And his whole exome sequencing (WES) examination suggested that CIITA gene was heterozygous mutation, a kind of MHC II deficiency diseases. After aggressive respiratory support and repeated adjustment of antimicrobial regimens, the patient was weaned from ventilator on the 56th day of admission and transferred to the immunology ward on the 60th day. The patient was successful discharged after hospitalizing for 91 days, taking antimicrobials orally to prevent infections post-discharge and waiting for stem cell transplantation. This case highlights the potential importance of NGS in providing better diagnostic testing for unexplained infection and illness. Furthermore, pathogens would be identified more accurately if conventional detection techniques were combined with mNGS

Whole exome sequencing identifies frequent somatic mutations in cell-cell adhesion genes in chinese patients with lung squamous cell carcinoma

Lung squamous cell carcinoma (SQCC) accounts for about 30% of all lung cancer cases. Understanding of mutational landscape for this subtype of lung cancer in Chinese patients is currently limited. We performed whole exome sequencing in samples from 100 patients with lung SQCCs to search for somatic mutations and the subsequent target capture sequencing in another 98 samples for validation. We identified 20 significantly mutated genes, including TP53, CDH10, NFE2L2 and PTEN. Pathways with frequently mutated genes included those of cell-cell adhesion/Wnt/Hippo in 76%, oxidative stress response in 21%, and phosphatidylinositol-3-OH kinase in 36% of the tested tumor samples. Mutations of Chromatin regulatory factor genes were identified at a lower frequency. In functional assays, we observed that knockdown of CDH10 promoted cell proliferation, soft-agar colony formation, cell migration and cell invasion, and overexpression of CDH10 inhibited cell proliferation. This mutational landscape of lung SQCC in Chinese patients improves our current understanding of lung carcinogenesis, early diagnosis and personalized therapy

Efficiency Evaluation and Influencing Factors Analysis of Logistics Industry based on Multiobjective Intelligent Computing

In logistics industry of 12 provinces along China’s new western land-sea corridor from 2010 to 2019, this research employed three-stage SBM model that considers undesirable output to measure logistics industrial efficiency and the panel Tobit model to investigate variables impacting logistics efficiency. The study found that after controlling for environmental variables and statistical noise, the logistics industrial efficiency in China’s new western land-sea corridor has improved, and the logistics sector efficiency of each province has spatial variability. Generally speaking, the south part goes up and the north part goes down; industrial structure, logistics transportation intensity, and economic development have a favorable influence on logistics sector efficiency. The urbanization rate, government support level, level of infrastructure, and degree of openness all have a negative influence on efficiency. Finally, relevant policy considerations such as logistics transport intensity, pure technical efficiency, scale efficiency, and external environment are proposed

Calculation on Bending Stiffness of RC Short Beam Strengthened by CFRP

Based on the bending tests of seven reinforced concrete (RC) short beams strengthened with carbon fiber reinforced polymer (CFRP), the bending stiffness curves of the whole process of the short beams strengthened with CFRP were obtained. The variation law of bending stiffness curve of short beam in the whole loading process was analyzed. Based on the reasonable calculation assumption, the calculation method of flexural rigidity of short reinforced concrete beams strengthened with CFRP sheets in the whole loading process was put forward. The comparison between the calculated value and the test value of bending stiffness showed that the calculation method of bending stiffness was reasonable and had high calculation accuracy. This calculation method can be used not only in the calculation of flexural rigidity of short reinforced concrete beams strengthened with CFRP sheets but also in the calculation of flexural rigidity of ordinary short reinforced concrete beams. The calculation method in this paper can provide a theoretical basis for the deformation calculation of reinforced concrete short beams strengthened with CFRP sheets

Seismic Behavior Analysis of Damaged Steel Fiber-Reinforced High-Strength Concrete Frame Joints Strengthened by FRP

In this paper, the seismic behavior of fiber-reinforced polymer (FRP) strengthened and unstrengthened steel fiber-reinforced high-strength concrete frame joints under low cyclic loading was tested. Then, the nonlinear finite element program was used to simulate the seismic behavior of FRP strengthened and unstrengthened steel fiber-reinforced high-strength concrete frame joints under low cyclic repeated load. The influence of FRP bond direction on the seismic behavior of steel fiber-reinforced high-strength concrete frame joints was studied. Through the comparison of the test values and numerical simulation values of the hysteretic curve, skeleton curve, energy dissipation capacity, displacement ductility, bearing capacity degradation, stiffness degradation, and other performance indexes of frame joints, the rule was obtained. The results showed that the 45° bonding direction of carbon fiber cloth is better than the 0° bonding direction, and the digital simulation results are in good agreement with the test results. Therefore, the constitutive model, element, end constraint, and loading method used in the finite element numerical simulation of this paper were reasonable, which can provide reference for the similar research in the future

Modeling of MOEMS electromagnetic scanning grating mirror for NIR micro-spectrometer

In this paper, the mathematical model is developed for researching the detailed electromagnetic mechanism of MOEMS scanning mirror. We present the relationship between spectral range and optical scanning angle. Furthermore, the variation tendencies of resonant frequency and maximal torsional angle are studied in detail under different aspect ratios of MOEMS scanning mirror and varied dimensions of torsional bar. The numerical results and Finite Element Analysis simulations both indicate that the thickness of torsional bar is the most important factor. The maximal torsional angle appears when the aspect ratio equals to 1. This mathematical model is an effective way for designing the MOEMS electromagnetic scanning grating mirror in actual fabrication

Effect of Heat Input on LMHMW Joint of Carbon Steel

Laser-MIG hybrid multi-layer welding (LMHMW) technology has been employed in paraxial configuration with laser leading for the welding of 20 mm thick Q235 carbon steel plates to exploit the hybridization effect that addresses the shortcomings of the individual process as well as to compliment their merits. The bilateral effects of arc augmented laser welding have resulted in complete joint penetration, process efficiency, stability and gap bridge ability. Samples welded under varying heat inputs in multiple passes have been analyzed for their microstructure evaluation using an optical microscope followed by tensile and Vickers hardness testing in various regions of the weld zones. This process was conducted to characterize the effect of heat input on the mechanical properties of the welded joints. The experimental results illustrate that different heat inputs have significant effects on the microstructure, heat affected zone width and mechanical properties of welded joints. The microhardness near the fusion line decreases dramatically due to the influence of the phase transformation process, and the highest microhardness value is obtained in the center of the weld seam. By using reasonable process parameters, the strength of the welded joint can obtain 458.5 MPa

Ralstonia solanacearum elicitor RipX Induces Defense Reaction by Suppressing the Mitochondrial atpA Gene in Host Plant

RipX of Ralstonia solanacearum is translocated into host cells by a type III secretion system and acts as a harpin-like protein to induce a hypersensitive response in tobacco plants. The molecular events in association with RipX-induced signaling transduction have not been fully elucidated. This work reports that transient expression of RipX induced a yellowing phenotype in Nicotiana benthamiana, coupled with activation of the defense reaction. Using yeast two-hybrid and split-luciferase complementation assays, mitochondrial ATP synthase F1 subunit α (ATPA) was identified as an interaction partner of RipX from N. benthamiana. Although a certain proportion was found in mitochondria, the YFP-ATPA fusion was able to localize to the cell membrane, cytoplasm, and nucleus. RFP-RipX fusion was found from the cell membrane and cytoplasm. Moreover, ATPA interacted with RipX at both the cell membrane and cytoplasm in vivo. Silencing of the atpA gene had no effect on the appearance of yellowing phenotype induced by RipX. However, the silenced plants improved the resistance to R. solanacearum. Moreover, qRT-PCR and promoter GUS fusion experiments revealed that the transcript levels of atpA were evidently reduced in response to expression of RipX. These data demonstrated that RipX exerts a suppressive effect on the transcription of atpA gene, to induce defense reaction in N. benthamiana