Physicians' use and perceptions of genetic testing for rare diseases in China: a nationwide cross-sectional study.

BACKGROUND: Genetic testing can facilitate the diagnosis and subsequent therapeutic management of rare diseases. However, there is a lack of data on the use of genetic testing for rare diseases. This study aims to describe the utilization rate and troubles encountered by clinicians in treating rare diseases with genetic testing. METHODS: A cross-sectional electronic questionnaire survey was conducted between June and October 2022 among the medical staff from the hospitals covering all provinces, municipalities, and autonomous regions of China. The survey on genetic testing focused on whether genetic testing was used in the diagnosis and treatment of rare diseases, the specific methods of genetic testing, and the problems encountered when using genetic testing. RESULTS: A total of 20,132 physicians who had treated rare diseases were included, of whom 35.5% were from the central region, 36.7% were from the eastern region, and 27.8% were from the western region. The total utilization rate of genetic testing for rare diseases was 76.0% (95%CI: 75.4-76.6). The use of genetic testing was highest in the Eastern region (79.2% [95% CI: 78.3-80.1]), followed by the Central (75.9% [95% CI: 74.9-76.9]) and Western regions (71.9% [95% CI: 70.7-73.1]). More than 90% (94.1% [95%CI: 93.4-94.8]) of pediatricians had used genetic testing to treat rare diseases, with surgeons having the lowest use of genetic testing (58.3% [95% CI: 56.6-60.0]). Physicians' departments and education levels affect the use of genetic testing. Most physicians have used a variety of genetic tests in the management of rare diseases, the most popular methods were "Whole-exome sequencing (Proband)" and "Whole-exome sequencing (families of three or more)". Doctors have encountered many problems with the use of genetic testing in the diagnosis and treatment of rare diseases, among which the high price was the main concern of medical workers. CONCLUSION: Three-quarters of physicians used genetic testing in rare disease practice, and there were regional differences in the use of genetic testing. Recognition of the utilization of genetic testing can help identify patterns of resource utilization in different regions and provide a more comprehensive picture of the epidemiology of rare diseases in jurisdictions.

An Experimental and Numerical Study of the Influence of Temperature on Mode II Fracture of a T800/Epoxy Unidirectional Laminate.

Studies on mode II fracture have promoted the establishment of the delamination theory for unidirectional composite laminates at room temperature. However, under thermal conditions, the fracture behavior of composite laminates will exhibit certain differences. The delamination theory should be extended to consider the temperature effect. To achieve this goal, in this study, the mode II static delamination growth behavior of an aerospace-grade T800/epoxy composite is investigated at 23 °C, 80 °C and 130 °C. The mode II fracture resistance curve (R-curve) is experimentally determined. A fractographic study on the fracture surface is performed using a scanning electron microscope (SEM), in order to reveal the failure mechanism. In addition, a numerical framework based on the cohesive zone model with a bilinear constitutive law is established for simulating the mode II delamination growth behavior at the thermal condition. The effects of the interfacial parameters on the simulations are investigated and a suitable value set for the interfacial parameters is determined. Good agreements between the experimental and numerical load-displacement responses illustrate the applicability of the numerical model. The research results provide helpful guidance for the design of composite laminates and an effective numerical method for the simulation of mode II delamination growth behavior.

Extracellular domain of human calcium sensing receptor immobilized to silica beads as biomaterial: A rapid chromatographic method for recognizing ligands from complex matrix 'Shuangdan'.

Human calcium-sensing receptor (CaSR), a member of the G-protein-coupled receptor superfamily (GPCR), has been a therapeutic target for developing new drugs against calciotropic disorders and non-calciotropic diseases. The highly efficient methodologies for pursuing novel ligands/drugs remained a challenge due to the redundant purification processes of membrane protein in some widely-used methods including NMR, X-ray crystallography, Fluorescence Titration Spectroscopy, and Circular Dichroism. Herein, extracellular domain (ECD) of CaSR as its functional fragment was used to develop a rapid chromatographic method, which involved the synthesis of stationary phase material based on the site-specific covalent reaction of Halogenated alkane dehalogenase (Halo)-tagged ECD of CaSR in cell lysate with 6-chlorocaproic acid modified silica beads, the use of the immobilized CaSR column for revealing the interaction of three known agonists with CaSR and further screening ligands from complex matrix like Chinese herb medicine 'Shuangdan'. The immobilized CaSR column was prepared rapidly without the protein purification and retained a good stability and specificity for at least 35 days. It was revealed that one type of binding sites occurred on CaSR with the binding affinity of neomycin > gentamicin-C / kanamycin, presumably which related to the number of structural amino groups attached. This method allowed for recognizing specifically novel ligands from 'Shuangdan', demonstrating one type of binding sites on CaSR with the binding affinity of gallic acid > caffeic acid > paeonol. These results indicated that, the immobilization of a representative extracellular domain of CaSR to silica beads as biomaterial is feasible to develop a new rapid method, which can be successfully applied in screening novel ligands efficiently from complex matrices.

Oxygen-Vacancy-Induced Synaptic Plasticity in an Electrospun InGdO Nanofiber Transistor for a Gas Sensory System with a Learning Function.

The perceptual learning function of a simulating human body is very important for constructing a neural computing system and a brainlike computer in the future. The sense of smell is an important part of the human sensory nervous system. However, current gas sensors simply convert gas concentrations into electrical signals and do not have the same learning and memory function as synapses. To solve this problem, we propose a new sensing idea to induce and activate the synaptic properties of transistors by adjusting the oxygen vacancy in the active layer. This sensor combines gas detection with synaptic memory and learning and overcomes the disadvantage of the separation of synaptic transistors and sensors, thus greatly reducing the cost of production. This work combines the detection of N,N-dimethylformamide (DMF) gas with the synaptic mechanism of human olfactory nerves. We successfully fabricated an InGdO nanofiber field-effect transistor by electrostatic spinning and simulated the response of human olfactory synapses to target gas by regulating the oxygen vacancy of the InGdO nanofiber. The synaptic transistor response under different concentrations of unmodulated pulses is tested, and the pavlovian conditioned reflex experiment is simulated successfully. This work provides a new idea of a gas sensor device, which is very important for the development of high-performance gas sensors and bionic electronic devices in the future.

Mg-doped InSnO nanofiber field-effect transistor for methanol gas detection at room temperature.

Research on high-performance gas sensors for detecting toxic and harmful methanol gas is still a very important issue. For gas sensors, it is very important to be able to achieve low concentration detection at room temperature. In this work, we used the electrospinning method to prepare Mg-doped InSnO nanofiber field-effect transistors (FETs) methanol gas sensor. When the Mg element doping concentration is 2.3 mol.%, InSnO nanofiber FET exhibits excellent electrical properties, including higher mobility of 3.17 cm2V-1s-1, threshold voltage of 1.51 V, subthreshold swing of 0.42 V/decade, the excellent on/off current ratio is about 108and the positive bias stress stability of the InSnO nanofiber FET through Mg doping has been greatly improved. In addition, the InSnMgO nanofiber FET gas sensor exhibits acceptable gas selectivity and sensitivity to methanol gas at room temperature. In the methanol gas sensor test at room temperature, when the methanol gas concentration is 60 ppm at room temperature, the response value of the InSnMgO nanofiber FET gas sensor is 81.92; and when the methanol concentration is 5 ppm, the response value is still 1.21. This work provides an effective and novel way to build a gas sensor at room temperature and use it to detect methanol gas at room temperature.

Rapidly identifying bioactive compounds from Zhisou oral liquid by immobilized receptor-based high-performance affinity chromatography.

The identification of bioactive compounds in complex matrices remains a major challenge due to the lack of highly efficient and specific methods. This work developed an approach based on high-performance affinity chromatography to identify the potential antitussive compounds from Zhisou oral liquid . The main methods include the synthesis of immobilized beta2-adrenoceptor by a one-step method, the screening and identification of the potential bioactive compounds by the receptor column coupled with mass spectrometry, and the binding mechanism analysis of the compounds to the receptor by the in vivo experiment, injection amount dependent method and molecular simulation. We identified the potential bioactive compounds of Zhisou oral liquid as glycyrrhizic acid, platycodin D, tuberostemonine, and hesperidin. In vivo experiment showed that the combinational utilization of the four compounds was possible to present an equivalent antitussive effect to the formula. The docking results demonstrated that hydrogen bonds and Van der Waals forces were the main forces to drive the binding of the four compounds to beta2-adrenoceptor. We concluded that the four compounds are the effective components in Zhisou oral liquid. The proposed strategy is possible to provide an alternative for the development of highly efficient methods to pursue the bioactive compounds of complex matrices.

High ionic conductivity Li0.33La0.557TiO3nanofiber/polymer composite solid electrolyte for flexible transparent InZnO synaptic transistors.

With the rapid development of wearable artificial intelligence devices, there is an increasing demand for flexible oxide neuromorphic transistors with the solid electrolytes. To achieve high-performance flexible synaptic transistors, the solid electrolytes should exhibit good mechanical bending characteristics and high ion conductivity. However, the polymer-based electrolytes with good mechanical bending characteristics show poor ion conductivity (10-6-10-7S cm-1), which limits the performance of flexible synaptic transistors. Thus, it is urgent to improve the ion conductivity of the polymer-based electrolytes. In the work, a new strategy of electrospun Li0.33La0.557TiO3nanofibers-enhanced ion transport pathway is proposed to simultaneously improve the mechanical bending and ion conductivity of polyethylene oxide/polyvinylpyrrolidone-based solid electrolytes. The flexible InZnO synaptic transistors with Li0.33La0.557TiO3nanofibers-based solid electrolytes successfully simulated excitatory post-synaptic current, paired-pulse-facilitation, dynamic time filter, nonlinear summation, two-terminal input dynamic integration and logic function. This work is a useful attempt to develop high-performance synaptic transistors.

Halo-tagged protein immobilization: Effect of halide linkers on peak profile and drug-protein interaction.

In previous work, we have established a one-step method to immobilize halo-tagged proteins onto microspheres through the covalent bond formed between the halo-tag and the halide linkers on the support surface. We observe extremely tailed peaks of most of drugs on the immobilized proteins, which is reasoned by the nonspecific interaction between the linkers and the drugs. To prove this, the current work designed five different halide linkers for the immobilization of beta2-adrenoceptor (ß2-AR). We applied the immobilized receptor to systematically realize the effects of these halide linkers on drug-receptor interaction by analyzing peak profiles of five drugs. The retention times and the half-widths of the drugs appeared to be negatively correlated to the atom numbers of the linkers in the range of 6-13 atoms. Subsequent increase of linker atoms resulted in reduced retention times and wider peaks of the drugs. Applying identical linker length, we observed clear reduced retention times and half-widths of the five drugs than the linker in the absence of oxygen atom. Such improvement was dominated by the number of oxygen atoms. These indicated that linker S-4 (2-(2-(2-(2-chloroethoxy) ethoxy) ethoxy) acetic acid) was optimal to eliminate the unwanted non-specific interactions. In comparison with the columns prepared by linker S-1 (6-chlorocaproic acid) and histidine tagged ß2-AR, the drugs on the linker S-4 column gave greater dissociation rate constants (e.g. 60.3±0.3 s-1 for salbutamol), which is closer to the data in literatures. Taking together, we concluded that optimization of the linker structure plays particular role in reducing the non-specific interaction between the immobilized protein and the drugs, thereby making the determination of drug-protein interaction more reliable.