Non-viral, specifically targeted CAR-T cells achieve high safety and efficacy in B-NHL.

Recently, chimeric antigen receptor (CAR)-T cell therapy has shown great promise in treating haematological malignancies1-7. However, CAR-T cell therapy currently has several limitations8-12. Here we successfully developed a two-in-one approach to generate non-viral, gene-specific targeted CAR-T cells through CRISPR-Cas9. Using the optimized protocol, we demonstrated feasibility in a preclinical study by inserting an anti-CD19 CAR cassette into the AAVS1 safe-harbour locus. Furthermore, an innovative type of anti-CD19 CAR-T cell with PD1 integration was developed and showed superior ability to eradicate tumour cells in xenograft models. In adoptive therapy for relapsed/refractory aggressive B cell non-Hodgkin lymphoma (ClinicalTrials.gov, NCT04213469 ), we observed a high rate (87.5%) of complete remission and durable responses without serious adverse events in eight patients. Notably, these enhanced CAR-T cells were effective even at a low infusion dose and with a low percentage of CAR+ cells. Single-cell analysis showed that the electroporation method resulted in a high percentage of memory T cells in infusion products, and PD1 interference enhanced anti-tumour immune functions, further validating the advantages of non-viral, PD1-integrated CAR-T cells. Collectively, our results demonstrate the high safety and efficacy of non-viral, gene-specific integrated CAR-T cells, thus providing an innovative technology for CAR-T cell therapy.

Ultra-sensitive pressure sensor with low-temperature crosstalk based on the Vernier effect and helical structure.

What we believe to be a novel high-sensitivity fiber-optic pressure sensor based on the vernier effect and helical structure is proposed and experimentally verified. The sensor utilizes the superposition of higher-order mode Mach-Zehnder interference and Sagnac fundamental mode polarization interference in a single fiber ring to achieve the vernier effect. In addition, a non-invasive encapsulation structure was fabricated to convert the rise and fall of the pressure value into the change in the twist angle of the optical fiber. This approach reduces the interference of the detecting medium on the sensor signal while simultaneously increasing the sensitivity of the pressure sensor. According to experimental data, the detection sensitivity of the sensor can reach -67277 nm/MPa, which is 65 times higher than the sensitivity of the conventional vernier effect pressure sensor. It also solves the issue of temperature interference with the Vernier-effect structured fiber optic sensor. The sensor has a measured temperature cross-sensitivity of 0.000065 kPa/°C, which is significantly lower than that of comparable sensors. This makes the sensor highly sensitive and ideal for low crosstalk pressure measurement.

Computed tomography-based contrast features for distinguishing extra-gastrointestinal stromal tumors from intra-abdominal fibromatosis.

PURPOSE: This study aims to define the computed tomography (CT) criteria that distinguish extra-gastrointestinal stromal tumors (eGISTs) from intra-abdominal fibromatosis (IAF). METHODS: Retrospective analysis was conducted on CT images obtained from 31 pathologically confirmed cases, including 17 cases of eGISTs and 14 of IAF. Various parameters [e.g., lesion location, contour characteristics, border delineation, enhancement patterns, presence of intralesional necrosis, vessels, air, fat, and hemorrhage, the long diameter (LD), LD/short diameter (SD) ratio, and volume (LD × SD × height diameter)] were meticulously evaluated. In addition, the degree of enhancement during arterial and portal venous phases and the lesion-to-aorta CT attenuation ratio during both phases were quantified. Statistical analysis was performed using Fisher's exact test, the Student's t-test, and the receiver operating characteristic curve to identify significant CT criteria. Sensitivity and specificity assessments were conducted for single and combined CT criteria. RESULTS: Significant differentiators between eGISTs and IAF include non-mesenteric localization, irregular contour, well-defined borders, heterogeneous enhancement, presence of intralesional necrosis and vessels, and absence of intralesional fat, with LD exceeding 9.6 cm, an LD/SD ratio >1.22, and volume surpassing 603.3 cm3 (P < 0.05). A combination of seven or more of these criteria yielded a specificity of 100%. CONCLUSION: Ten distinct CT criteria have been identified to distinguish eGISTs from IAF, notably encompassing non-mesenteric localization, irregular contour, well-defined borders, heterogeneous enhancement, presence of intralesional necrosis and vessels, absence of intralesional fat, LD >9.6 cm, an LD/SD ratio >1.22, and volume surpassing 603.3 cm3. CLINICAL SIGNIFICANCE: The current findings establish CT criteria to distinguish eGISTs from IAF in a clinical setting.

[Prenatal diagnosis and clinical counseling for fetal chromosomal reciprocal translocations].

OBJECTIVE: To analyze the clinical effect of fetal chromosomal reciprocal translocation in order to optimize procedures for prenatal diagnosis and clinical counseling. METHODS: Conventional G-banding karyotype analysis was performed on 7901 amniotic fluid samples. For fetuses found to have carried a reciprocal translocation, karyotypes of their parents were checked. Fetuses with de novo translocations also underwent microarray analysis to exclude small deletions, and were subjected to prenatal ultrasound monitoring till birth and one year follow-up. Those with de novo translocations were followed till 3 years old. RESULTS: A total of 24 fetal reciprocal translocations have been identified, which gave a detection rate of 0.30%. Analysis of parental karyotypes has found reciprocal translocations in 17 cases, including 9 maternal and 8 paternal cases. The remaining 4 were of de novo mutations, for which parental examination was refused in three cases. For fetuses with inherited translocations, prenatal ultrasound monitoring and follow-up results were all normal. For those with de novo translocations, although gene chip analysis has failed to detect copy number variations (CNVs), prenatal ultrasound and follow-up results had found three with abnormal outcome. These included 1 case with reciprocal translocation involving the X chromosome and an autosome. CONCLUSION: For prenatally detected reciprocal chromosome translocations, parental origin should be traced. Gene chip analysis can help to exclude small deletions and duplications. However, ultrasound monitoring and follow-up after birth are equally important. Based on comprehensive analysis of the results of combined testing, accurate counseling can be provided.

Design of Table Tennis Training Competition Knowledge Interaction Platform Integrating Improved Swarm Intelligence Algorithm.

Table tennis is China 's national game and the proudest sport in China's sports field. During the research and technology service work of the Chinese table tennis team for many years, it has accumulated a large amount of valuable data on the analysis of skills and tactics of training and matches, match video, training monitoring, and so on. This paper discusses the relevant theory of swarm intelligence algorithm processing big data on the table tennis training competition knowledge interaction platform system, as well as the technical support of Nginx and Tomcat, and determines the technical basis of the table tennis training competition knowledge interaction platform. Through the establishment of the firefly algorithm model, the resource search ability is enhanced, and the traditional firefly algorithm is improved. From the results of the system performance test, it can be found that the improved swarm intelligence algorithm adopted in this paper improves the global convergence, and the load balancing degree gradually decreases with the increase of time. The improved firefly algorithm shows good performance when the bandwidth is low, and the resource occupancy rate is greatly reduced. When the bandwidth is 20, it is reduced by 12.55%. It solves the shortcomings of long time and low success rate, so as to verify the convenience of the system operation and the power of functions and make the platform more intelligent and efficient.

Prediction of Srebp-1 as a Key Target of Qing Gan San Against MAFLD in Rats via RNA-Sequencing Profile Analysis.

Metabolism-associated fatty liver disease (MAFLD) is the most common chronic liver disease worldwide, and the use of traditional Chinese medicines (TCMs) to treat this disease has attracted increasing attention. The Qing Gan San (QGS) formula comprises Polygonatum sibiricum, the peel of Citrus reticulata Blanco, the leaves of Morus alba L, Cichorium intybus, Glycyrrhiza uralensis Fisch, and Cirsium setosum. The present study aimed to uncover the anti-hyperlipidaemic effects, hepatic fat accumulation-lowering effects and mechanisms of QGS in high-fat diet-induced MAFLD rats. QGS significantly reduced the levels of total cholesterol and triglycerides in both serum and liver tissue and partially protected hepatic function. Additionally, QGS significantly ameliorated hepatic lipid accumulation with histopathology observation, as demonstrated by H&E and oil red O staining. RNA sequencing was used to further investigate the key genes involved in the development and treatment of MAFLD. Hierarchical clustering analysis showed that the gene expression profiles in rats with MAFLD were reversed to normal after QGS treatment. QGS had 222 potential therapeutic targets associated with MAFLD. Enrichment analysis among these targets revealed that QGS affected biological functions/pathways such as the regulation of lipid metabolic processes (GO: 0019216) and the non-alcoholic fatty liver disease pathway (hsa04932), and identified Srebp-1 as a key regulator in the synthesis of cholesterol and triglycerides. Subsequently, both immunofluorescence and Western blot analyses demonstrated that QGS suppressed the transfer of Srebp-1 to the nucleus from the cytoplasm, suggesting that the activation of Srebp-1 was inhibited. Our study reveals the effects and mechanisms of QGS in the treatment of MAFLD and provides insights and prospects to further explore the pathogenesis of MAFLD and TCM therapies.