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The article discusses the use of the ISDra2-TnpB system, a compact bacterial protein, for efficient genome editing in vitro and in vivo. The authors demonstrate that ISDra2-TnpB can successfully edit genes in human and mouse cells, resulting in targeted mutations. They also introduce a truncated version of TnpB, called supermini TnpB, which exhibits efficient gene editing capabilities. The study highlights the potential of ISDra2-TnpB and its truncated variant as versatile tools for genome editing applications. [Extracted from the article]

This document is a letter published in the journal Neurological Sciences. The authors conducted a study using Mendelian randomization analysis to explore the causal relationship between 25-hydroxyvitamin D (25(OH)D) levels and the risk of developing neuromyelitis optica spectrum disorder (NMOSD). They used genome-wide association study (GWAS) data on NMOSD and 25(OH)D levels to analyze the genetic variations and their effects on the disease. The results showed no strong evidence of a causal association between 25(OH)D levels and NMOSD risk in a population of European ancestry. However, a causal relationship was observed between genetically predicted 25(OH)D levels and AQP4-ab-positive NMOSD risk. The study suggests that low vitamin D levels may be a risk factor for AQP4-ab-positive NMOSD and highlights the importance of further research in this area. [Extracted from the article]

Keywords: Enlarged perivascular spaces; Glial fibrillary acidic protein astrocytopathy; Magnetic resonance imaging EN Enlarged perivascular spaces Glial fibrillary acidic protein astrocytopathy Magnetic resonance imaging 3751 3754 4 09/13/23 20231001 NES 231001 Shugang Cao and Yunfei Zhu contributed equally to this work. 1K, L) were noted on brain MRI; spinal MRI showed a significant reduction in spinal cord lesions (Fig. Non-enhanced brain MRI in 2020 suggested marked progression of paraventricular lesions with EPVSs (E, F) and contrast-enhanced MRI demonstrated linear perivascular radial gadolinium enhancement (G, H thick arrows). [Extracted from the article]

Ankylosing spondylitis (AS) is a chronic inflammatory disease that causes inflammatory low back pain and may even limit activity. The grading diagnosis of sacroiliitis on imaging plays a central role in diagnosing AS. However, the grading diagnosis of sacroiliitis on computed tomography (CT) images is viewer-dependent and may vary between radiologists and medical institutions. In this study, we aimed to develop a fully automatic method to segment sacroiliac joint (SIJ) and further grading diagnose sacroiliitis associated with AS on CT. We studied 435 CT examinations from patients with AS and control at two hospitals. No-new-UNet (nnU-Net) was used to segment the SIJ, and a 3D convolutional neural network (CNN) was used to grade sacroiliitis with a three-class method, using the grading results of three veteran musculoskeletal radiologists as the ground truth. We defined grades 0–I as class 0, grade II as class 1, and grades III–IV as class 2 according to modified New York criteria. nnU-Net segmentation of SIJ achieved Dice, Jaccard, and relative volume difference (RVD) coefficients of 0.915, 0.851, and 0.040 with the validation set, respectively, and 0.889, 0.812, and 0.098 with the test set, respectively. The areas under the curves (AUCs) of classes 0, 1, and 2 using the 3D CNN were 0.91, 0.80, and 0.96 with the validation set, respectively, and 0.94, 0.82, and 0.93 with the test set, respectively. 3D CNN was superior to the junior and senior radiologists in the grading of class 1 for the validation set and inferior to expert for the test set (P < 0.05). The fully automatic method constructed in this study based on a convolutional neural network could be used for SIJ segmentation and then accurately grading and diagnosis of sacroiliitis associated with AS on CT images, especially for class 0 and class 2. The method for class 1 was less effective but still more accurate than that of the senior radiologist. [ABSTRACT FROM AUTHOR]

Actuator plays a significant role in soft robotics. This paper proposed an ultralong stretchable soft actuator (US2A) with a variable and sizeable maximum elongation. The US2A is composed of a silicone rubber tube and a bellows woven sleeve. The maximal extension can be conveniently regulated by just adjusting the wrinkles' initial angle of the bellows woven sleeve. The kinematics of US2A could be obtained by geometrically analyzing the structure of the bellows woven sleeve when the silicone rubber tube is inflated. Based on the principle of virtual work, the actuating models have been established: the pressure-elongation model and the pressure-force model. These models reflect the influence of the silicone tube's shell thickness and material properties on the pneumatic muscle's performance, which facilitates the optimal design of US2A for various working conditions. The experimental results showed that the maximum elongation of the US2A prototype is 257%, and the effective elongation could be variably regulated in the range of 0 and 257%. The proposed models were also verified by pressure-elongation and pressure-force experiments, with an average error of 5% and 2.5%, respectively. Finally, based on the US2A, we designed a pneumatic rehabilitation glove, soft arm robot, and rigid-soft coupling continuous robot, which further verified the feasibility of US2A as a soft driving component. [ABSTRACT FROM AUTHOR]

Ribosomes are highly sophisticated translation machines that have been demonstrated to be heterogeneous in the regulation of protein synthesis1,2. Male germ cell development involves complex translational regulation during sperm formation3. However, it remains unclear whether translation during sperm formation is performed by a specific ribosome. Here we report a ribosome with a specialized nascent polypeptide exit tunnel, RibosomeST, that is assembled with the male germ-cell-specific protein RPL39L, the paralogue of core ribosome (RibosomeCore) protein RPL39. Deletion of RibosomeST in mice causes defective sperm formation, resulting in substantially reduced fertility. Our comparison of single-particle cryo-electron microscopy structures of ribosomes from mouse kidneys and testes indicates that RibosomeST features a ribosomal polypeptide exit tunnel of distinct size and charge states compared with RibosomeCore. RibosomeST predominantly cotranslationally regulates the folding of a subset of male germ-cell-specific proteins that are essential for the formation of sperm. Moreover, we found that specialized functions of RibosomeST were not replaceable by RibosomeCore. Taken together, identification of this sperm-specific ribosome should greatly expand our understanding of ribosome function and tissue-specific regulation of protein expression pattern in mammals.RibosomeST—a ribosome with a specialized nascent polypeptide exit tunnel—cotranslationally regulates the folding of a subset of male germ-cell-specific proteins that are essential for the formation of sperm. [ABSTRACT FROM AUTHOR]

The complexity and concealment of the goaf environment hinder the understanding of the types of ignition sources in goaf gas explosions. Therefore, this study constructed a mechanical-electrical test system for rocks; the generation of pressure stimulated currents (PSCs) and its discharge-induced ignition mechanism of roof sandstone under uniaxial compression were explored, and the real ignition source of the gas explosion accident in Babao Coal Mine was revealed. The experimental results reveal that the intensity of PSCs of sandstone is higher than that of marble in the loading stage because the piezoelectric effect of quartz in sandstone enhances its mechanical-electrical sensitivity and leads to an increase in the discharge intensity. During the whole loading stage, the PSCs signals generated by sandstone are mainly attributable to the piezoelectric effect of quartz, while the PSCs of marble are mainly caused by the sliding friction between mineral particles. When the samples are in the compaction and elastic stages, PSCs are proportional to strain rate and stress rate respectively; when the samples enter the stage of plastic deformation and failure, the peak values of PSCs are positively correlated with the uniaxial compressive strength. Sparks can be seen in sandstone during the failure stage, which mainly results from electron avalanche caused by the damage of quartz grains under loading. The ignition source of the gas explosion accident in Babao Coal Mine is more likely to be sparks generated by the combined discharge of the extrusion friction and piezoelectric effect of roof sandstone, rather than coal spontaneous combustion. [ABSTRACT FROM AUTHOR]

Ilamycins E1/E2 are novel cyclic heptapeptides from Streptomyces atratus SCSIO ZH16, which have the MIC value of 9.8 nM against Mycobacterium tuberculosis H37Rv. However, the lower fermentative titer of ilamycins E1/E2 cut off further development for novel anti-TB lead drugs. In order to break the obstacle, the combinatorial strategy of medium optimization, fermentative parameters optimization, exogenous addition of metal ions, precursors, and surfactants was developed to promoted the production of ilamycins E1/E2. Addition of 1 mM ZnCl2 at 0 h, 1 g/L tyrosine at 96 h, and 2 g/L shikimic acid at 48 h increased the production of ilamycins E1/E2 from 13.51 to 762.50 ± 23.15, 721.39 ± 19.13, and 693.83 ± 16.86 mg/L, respectively. qRT-PCR results showed that the transcription levels of key genes in Embden–Meyerhof–Parnas pathway, hexose phosphate shunt pathway, and shikimic acid pathway were upregulated. In addition, the production of ilamycins E1/E2 reached 790.34 mg/L in a 5-L bioreactor by combinatorial strategy. Combinatorial strategies were used for improving ilamycins E1/E2 production in S. atratus ΔilaR and provided a sufficient basis on further clinic development. [ABSTRACT FROM AUTHOR]

Glycine betaine is one of the most effective compatible solutes of the halophilic lactic acid bacterium Tetragenococcus halophilus, the transportation of which is essential for its survival under salinity stress condition. In the current study, we attempted to define a glycine betaine ABC transporter system of T. halophilus, busATha, which plays an important role in adapting to salinity condition. The expression of busATha enhanced the growth of the recombinant strain under high salinity. BusRTha, a transcription regulator that represses the expression of busATha, was characterized, and the repression was abrogated under high salinity. The binding of the regulator was demonstrated through electrophoretic mobility shift assays, and the binding sites were characterized as 5′-AAA(T/G)TGAC(C/A)(G/A)T(C/A)C-3′. This is the first studied transcription regulator of T. halophilus, and our findings provide insights into the molecular mechanism of halophilic life and tools for further application of halophiles as chassis in industrial biotechnology. [ABSTRACT FROM AUTHOR]