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T cell immunotherapy remains an attractive approach for cancer immunotherapy. T cell immunotherapy mainly employs chimeric antigen receptor (CAR)- and T cell receptor (TCR)-engineered T cells. CAR-T cell therapy has been an essential breakthrough in treating hematological malignancies. TCR-T cells can recognize antigens expressed both on cell surfaces and in intracellular compartments. Although TCR-T cells have not been approved for clinical application, a number of clinical trials have been performed, particularly for solid tumors. In this article, we summarized current TCR-T cell advances and their potential advantages for solid tumor immunotherapy. [ABSTRACT FROM AUTHOR]

Background: Jasmonate ZIM-domain (JAZ) proteins, which act as negative regulators in the jasmonic acid (JA) signalling pathway, have significant implications for plant development and response to abiotic stress. Results: Through a comprehensive genome-wide analysis, a total of 20 members of the JAZ gene family specific to alfalfa were identified in its genome. Phylogenetic analysis divided these 20 MsJAZ genes into five subgroups. Gene structure analysis, protein motif analysis, and 3D protein structure analysis revealed that alfalfa JAZ genes in the same evolutionary branch share similar exon‒intron, motif, and 3D structure compositions. Eight segmental duplication events were identified among these 20 MsJAZ genes through collinearity analysis. Among the 32 chromosomes of the autotetraploid cultivated alfalfa, there were 20 MsJAZ genes distributed on 17 chromosomes. Extensive stress-related cis-acting elements were detected in the upstream sequences of MsJAZ genes, suggesting that their response to stress has an underlying function. Furthermore, the expression levels of MsJAZ genes were examined across various tissues and under the influence of salt stress conditions, revealing tissue-specific expression and regulation by salt stress. Through RT‒qPCR experiments, it was discovered that the relative expression levels of these six MsJAZ genes increased under salt stress. Conclusions: In summary, our study represents the first comprehensive identification and analysis of the JAZ gene family in alfalfa. These results provide important information for exploring the mechanism of JAZ genes in alfalfa salt tolerance and identifying candidate genes for improving the salt tolerance of autotetraploid cultivated alfalfa via genetic engineering in the future. [ABSTRACT FROM AUTHOR]

Background: Nitrate (NO3−) is the major source of nitrogen (N) for higher plants aside from its function in transducing the N signaling. Improving N use efficiency of crops has been an effective strategy for promotion of the sustainable agriculture worldwide. The regulatory pathways associating with N uptake and the corresponding biochemical processes impact largely on plant N starvation tolerance. Thus, exploration of the molecular mechanism underlying nitrogen use efficiency (NUE) and the gene wealth will pave a way for molecular breeding of N starvation-tolerant crop cultivars. Results: In the current study, we characterized the function of TaNBP1, a guanine nucleotide-binding protein subunit beta gene of wheat (T. aestivum), in mediating the plant N starvation response. TaNBP1 protein harbors a conserved W40 domain and the TaNBP1-GFP (green fluorescence protein) signals concentrate at positions of cytoplasm membrane and cytosol. TaNBP1 transcripts are induced in roots and leaves upon N starvation stress and that this upregulated expression is recovered by N recovery treatment. TaNBP1 overexpression confers improved phenotype, enlarged root system architecture (RSA), and increased biomass for plants upon N deprivation relative to the wild type, associating with its role in enhancing N accumulation and improving reactive oxygen species (ROS) homeostasis. Nitrate transporter (NRT) gene NtNRT2.2 and antioxidant enzyme genes NtSOD1, NtSOD2, and NtCAT1 are transcriptionally regulated under TaNBP1 and contribute to the improved N acquisition and the increased AE activities of plants. Conclusions: Altogether, TaNBP1 is transcriptional response to N starvation stress. Overexpression of this gene enhances plant N starvation adaptation via improvement of N uptake and cellular ROS homeostasis by modifying transcription of NRT gene NtNRT2.2 and antioxidant enzyme genes NtSOD1, NtSOD2, and NtCAT1, respectively. Our research helps to understand the mechanism underlying plant N starvation response and benefits to genetically engineer crop cultivars with improved NUE under the N-saving cultivation conditions. [ABSTRACT FROM AUTHOR]

Background: Plant Architecture Related Traits (PATs) are of great importance for maize breeding, and mainly controlled by minor effect quantitative trait loci (QTLs). However, cloning or even fine-mapping of minor effect QTLs is very difficult in maize. Theoretically, large population and high density genetic map can be helpful for increasing QTL mapping resolution and accuracy, but such a possibility have not been actually tested. Results: Here, we employed a genotyping-by-sequencing (GBS) strategy to construct a linkage map with 16,769 marker bins for 1021 recombinant inbred lines (RILs). Accurately mapping of well studied genes P1, pl1 and r1 underlying silk color demonstrated the map quality. After QTL analysis, a total of 51 loci were mapped for six PATs. Although all of them belong to minor effect alleles, the lengths of the QTL intervals, with a minimum and median of 1.03 and 3.40 Mb respectively, were remarkably reduced as compared with previous reports using smaller size of population or small number of markers. Several genes with known function in maize were shown to be overlapping with or close neighboring to these QTL peaks, including na1, td1, d3 for plant height, ra1 for tassel branch number, and zfl2 for tassel length. To further confirm our mapping results, a plant height QTL, qPH1a, was verified by an introgression lines (ILs). Conclusions: We demonstrated a method for high resolution mapping of minor effect QTLs in maize, and the resulted comprehensive QTLs for PATs are valuable for maize molecular breeding in the future. [ABSTRACT FROM AUTHOR]

Background: Alfalfa (Medicago sativa) is a widely cultivated plant. Unlike many crops, the main goal of breeding alfalfa is to increase its aboveground biomass rather than the biomass of its seeds. However, the low yield of alfalfa seeds limits alfalfa production. Many studies have explored the factors affecting seed development, in which phytohormones, especially ABA and GAs, play an important role in seed development. Results: Here, we performed a transcriptome analysis of alfalfa seeds at five development stages. A total of 16,899 differentially expressed genes (DEGs) were identified and classified into 10 clusters, and the enriched Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were determined. The contents of ABA, GA1, GA3, GA4 and GA7 in alfalfa seeds at five development stages were determined. In addition, 14 ABA-related DEGs and 20 GA-related DEGs were identified and analysed. These DEGs are involved in plant hormone pathways and play an important role in seed development. Moreover, morphological and physiological analyses revealed the dynamic changes during the development of alfalfa seeds. Conclusion: Overall, our study is the first to analyse the transcriptome across various stages of seed development in alfalfa. The results of our study could be used to improve alfalfa seed yield. The key ABA and GA related-genes are potential targets for improving alfalfa seed yield via genetic engineering in the future. [ABSTRACT FROM AUTHOR]

Background: Cathelicidin/LL-37 plays a significant role in the human immune defense reaction. Preterm human immature organs being exposed to inflammation-induced injury was the critical denominator leading to the common preterm associated complications. Previous study showed LL37 concentration in preterm neonates was lower in tracheal aspirates and breast milk as compared to term infants. An adults study showed decreased LL-37 levels was a risk factor for patients in developing severe chronic obstructive pulmonary disease (COPD). However, little is known about the regulation of human cord blood LL37 in preterm neonates and the association with preterm complications. This study was designed to investigate the concentration of LL37 in cord blood of preterm infants and correlation with preterm complications. Methods: Singleton infants born in June 2017 to August 2021 in the study hospital were enrolled. Maternal and neonatal clinical characteristics were collected. LL37 levels, pro-inflammatory factor interleukin-6 (IL-6) and tumor necrosis factor-a (TNF-a) in cord blood and LL37 levels in serum 48–72 hours after birth were measured by enzyme-linked immunosorbent assay. The serum level of LL37 in preterm and term neonates were compared, the perinatal factors possibly affecting the LL37 levels were investigated and the relationship between LL37 level and preterm outcomes were analyzed. Results: Cord blood LL37 levels in preterm infants were lower than that in term neonates. Cord blood LL37 level was positively correlated with gestational age in preterm. Prenatal steroid administration in preterm neonates decreased cord blood LL37 level. LL37 level was obviously lower in patients with bronchopulmonary dysplasia (BPD). Multiple line regression analysis showed higher LL37 level in cord blood was an independent protective factor for BPD. The concentration of pro-inflammatory factor IL-6 was negatively correlated with LL37. Conclusion: Cord blood LL37 levels increased during gestation and decreased after perinatal steroid usage. Very preterm infants who displayed higher cord blood LL37 level had reduced risk of developing BPD. Regulation of pro-inflammatory cytokine IL-6 may be associated with the protective effect of LL37 on BPD. [ABSTRACT FROM AUTHOR]

Background: Lots of studies have measured motor evoked potential (MEP) induced by transcranial magnetic stimulation (TMS) in anesthetized animals. However, in awake animals, the measurement of TMS-induced MEP is scarce as lack of sufficient restraint. So far, the explicit study of anesthesia effects on corticospinal excitability and repetitive TMS (rTMS) induced modulation is still lacking. This study aimed to: (1) measure TMS-induced MEP in both awake restrained and anesthetized rats, (2) investigate the effect of anesthesia on corticospinal excitability, and (3) on rTMS-induced modulation. Methods: MEP of eighteen rats were measured under both wakefulness and anesthesia using flexible binding and surface electrodes. Peak-to-peak MEP amplitudes, resting motor threshold (RMT) and the slope of stimulus response (SR) were extracted to investigate anesthesia effects on corticospinal excitability. Thereafter, 5 or 10 Hz rTMS was applied with 600 pulses, and the increase in MEP amplitude and the decrease in RMT were used to quantify rTMS-induced modulation. Results: The RMT in the awake condition was 44.6 ± 1.2% maximum output (MO), the peak-to-peak MEP amplitude was 404.6 ± 48.8 μV at 60% MO. Under anesthesia, higher RMT (55.6 ± 2.9% MO), lower peak-to-peak MEP amplitudes (258.6 ± 32.7 μV) and lower slope of SR indicated that the corticospinal excitability was suppressed. Moreover, under anesthesia, high-frequency rTMS still showed significant modulation of corticospinal excitability, but the modulation of MEP peak-to-peak amplitudes was weaker than that under wakefulness. Conclusions: This study measured TMS-induced MEP in both awake and anesthetized rats, and provided explicit evidence for the inhibitory effects of anesthesia on corticospinal excitability and on high-frequency rTMS-induced modulation of MEP. [ABSTRACT FROM AUTHOR]

Background: Alfalfa, the "queen of forage", is the most extensively cultivated forage legume in the world. The development and yield of alfalfa are seriously limited by abiotic stress. MADS-box transcription factors are one of the largest gene families and play a pivotal role in plant development and abiotic stress. However, little is known regarding the MADS-box transcription factors in autotetraploid cultivated alfalfa. Results: In the present study, we identified 120 MsMADS-box genes in the alfalfa genome. Phylogenetic analysis indicated that 75 type-I MsMADS-box genes were classified into the Mα, Mβ, and Mγ subgroups, and 45 type-II MsMADS-box genes were classified into 11 subgroups. The promoter region of MsMADS-box genes containing several hormone and stress related elements. Chromosomal location analysis revealed that 117 MsMADS-box genes were unevenly distributed on 32 chromosomes, and the remaining three genes were located on unmapped scaffolds. A total of nine pairs of segmental duplications and four groups of tandem duplications were found. Expression analysis showed that MsMADS-box genes were differentially expressed in various tissues and under abiotic stresses. qRT-PCR analysis revealed that the expression profiles of eight selected MsMADS-box genes were distinct under various stresses. Conclusions: In this study, MsMADS-box genes were identified in the cultivated alfalfa genome based on autotetraploid level, and further confirmed by Gene Ontology (GO) analysis, phylogenetic analysis, sequence features and expression analysis. Taken together, these findings will provide clues for further study of MsMADS-box functions and alfalfa molecular breeding. Our study is the first to systematically identify and characterize the MADS-box transcription factors in autotetraploid cultivated alfalfa (Medicago sativa L.), and eight MsMADS-box genes were significantly involved in response to various stresses. [ABSTRACT FROM AUTHOR]

Background: Cells show directed migration response to electric signals, namely electrotaxis or galvanotaxis. PI3K and PTEN jointly play counterbalancing roles in this event via a bilateral regulation of PIP3 signaling. PI3K has been proved essential in anterior signaling of electrotaxing cells, whilst the role of PTEN remains elusive. Methods: Dictyostelium cells with different genetic backgrounds were treated with direct current electric signals to investigate the genetic regulation of electrotaxis. Results: We demonstrated that electric signals promoted PTEN phosphatase activity and asymmetrical translocation to the posterior plasma membrane of the electrotaxing cells. Electric stimulation produced a similar but delayed rear redistribution of myosin II, immediately before electrotaxis started. Actin polymerization is required for the asymmetric membrane translocation of PTEN and myosin. PTEN signaling is also responsible for the asymmetric anterior redistribution of PIP3/F-actin, and a biased redistribution of pseudopod protrusion in the forwarding direction of electrotaxing cells. Conclusions: PTEN controls electrotaxis by coordinately regulating asymmetric redistribution of myosin to the posterior, and PIP3/F-actin to the anterior region of the directed migration cells. [ABSTRACT FROM AUTHOR]

Background: Graphene oxide (GO), a novel carbon-based nanomaterial, has promising applications in biomedicine. However, it induces potential cytotoxic effects on the gastrointestinal (GI) tract cells, and these effects have been largely uncharacterized. The present study aimed to explore the toxic effects of GO on the intestinal tract especially under pre-existing inflammatory conditions, such as inflammatory bowel disease (IBD), and elucidate underlying mechanisms. Results: Our findings indicated that oral gavage of GO worsened acute colitis induced by 2.5% dextran sodium sulfate (DSS) in mice. In vitro, GO exacerbated DSS-induced inflammation and apoptosis in the FHC cell line, an ideal model of intestinal epithelial cells (IECs). Further, the potential mechanism underlying GO aggravated mice colitis and cell inflammation was explored. Our results revealed that GO treatment triggered apoptosis in FHC cells through the activation of reactive oxygen species (ROS)/AMP-activated protein kinase (AMPK)/p53 pathway, as evidenced by the upregulation of cytochrome c (Cytc), Bax, and cleaved caspase-3 (c-cas3) and the downregulation of Bcl-2. Interestingly, pretreatment with an antioxidant, N-acetyl-L-cysteine, and a specific inhibitor of AMPK activation, Compound C (Com.C), effectively inhibited GO-induced apoptosis in FHC cells. Conclusions: Our data demonstrate that GO-induced IECs apoptosis via ROS/AMPK/p53 pathway activation accounts for the exacerbation of colitis in vivo and aggravation of inflammation in vitro. These findings provide a new insight into the pathogenesis of IBD induced by environmental factors. Furthermore, our findings enhance our understanding of GO as a potential environmental toxin, which helps delineate the risk of exposure to patients with disturbed intestinal epithelial barrier/inflammatory disorders such as IBD. [ABSTRACT FROM AUTHOR]

Background: Alfalfa is the most extensively cultivated forage legume. Salinity is a major environmental factor that impacts on alfalfa's productivity. However, little is known about the molecular mechanisms underlying alfalfa responses to salinity, especially the relative contribution of the two important components of osmotic and ionic stress. Results: In this study, we constructed the first full-length transcriptome database for alfalfa root tips under continuous NaCl and mannitol treatments for 1, 3, 6, 12, and 24 h (three biological replicates for each time points, including the control group) via PacBio Iso-Seq. This resulted in the identification of 52,787 full-length transcripts, with an average length of 2551 bp. Global transcriptional changes in the same 33 stressed samples were then analyzed via BGISEQ-500 RNA-Seq. Totals of 8861 NaCl-regulated and 8016 mannitol-regulated differentially expressed genes (DEGs) were identified. Metabolic analyses revealed that these DEGs overlapped or diverged in the cascades of molecular networks involved in signal perception, signal transduction, transcriptional regulation, and antioxidative defense. Notably, several well characterized signalling pathways, such as CDPK, MAPK, CIPK, and PYL-PP2C-SnRK2, were shown to be involved in osmotic stress, while the SOS core pathway was activated by ionic stress. Moreover, the physiological shifts of catalase and peroxidase activity, glutathione and proline content were in accordance with dynamic transcript profiles of the relevant genes, indicating that antioxidative defense system plays critical roles in response to salinity stress. Conclusions: Overall, our study provides evidence that the response to salinity stress in alfalfa includes both osmotic and ionic components. The key osmotic and ionic stress-related genes are candidates for future studies as potential targets to improve resistance to salinity stress via genetic engineering. [ABSTRACT FROM AUTHOR]

Background: Magneto-acoustic tomography with current injection involves using electrical impedance imaging technology. To explore the potential applications in imaging biological tissue and enhance image quality, a new scan mode for the transducer is proposed that is based on translational and circular scanning to record acoustic signals from sources.Methods: An imaging algorithm to analyze these signals is developed in respect to this alternative scanning scheme. Numerical simulations and physical experiments were conducted to evaluate the effectiveness of this scheme. An experiment using a graphite sheet as a tissue-mimicking phantom medium was conducted to verify simulation results. A pulsed voltage signal was applied across the sample, and acoustic signals were recorded as the transducer performed stepped translational or circular scans. The imaging algorithm was used to obtain an acoustic-source image based on the signals.Results: In simulations, the acoustic-source image is correlated with the conductivity at the sample boundaries of the sample, but image results change depending on distance and angular aspect of the transducer. In general, as angle and distance decreases, the image quality improves. Moreover, experimental data confirmed the correlation.Conclusion: The acoustic-source images resulting from the alternative scanning mode has yielded the outline of a phantom medium. This scan mode enables improvements to be made in the sensitivity of the detecting unit and a change to a transducer array that would improve the efficiency and accuracy of acoustic-source images. [ABSTRACT FROM AUTHOR]

Background: An earthquake struck Ludian in Yunnan province of China on August 3, 2014, resulting in 3143 injuries, 617 deaths, and 112 missing persons. Our study aimed at estimating the quality of life and associated determinants among medical rescuers after Ludian earthquake.Methods: A cross-sectional survey was performed among personnel from three hospitals that assumed rescue tasks in Ludian earthquake. Descriptive statistics, t-tests, ANOVA and stepwise linear regression analysis were used for data analysis.Results: The mean scores on the physical component summary (PCS) and mental component summary (MCS) were 49.86 (SD = 6.01) and 35.85(SD = 6.90), respectively. Lower PCS in the aftermath of an earthquake was associated with non-military medical rescuers, elderly age, and being trapped/in danger while lower MSC in the aftermath of an earthquake was associated with non-military medical rescuers, young age, being female, being trapped/in danger and low education degree.Conclusions: In conclusion, our study demonstrates that medical rescuers are at risk for a lower HRQoL after exposure to Ludian earthquake. The results of this study help expand our knowledge of health-related quality of life among medical rescuers after the Ludian earthquake. [ABSTRACT FROM AUTHOR]

Reference 1 Song B, Gu Y, Jiang W, Li Y, Ayre WN, Liu Z, Yin T, Janetopolous C, Iijima M, Devreotes P, Zhao M. Electric signals counterbalanced posterior vs anterior PTEN signaling in directed migration of Dictyostelium. Correction to: Cell Biosci (2021) 11:111 https://doi.org/10.1186/s13578-021-00580-x In this article, the affiliation 'Department of Ophthalmology & Vision Science, UC Davis, School of Medicine, Davis CA 95618, USA' for Author Min Zhao was missing. [Extracted from the article]

Background: Robotized transcranial magnetic stimulation (TMS) combines the benefits of neuro-navigation with automation and provides a precision brain stimulation method. Since the coil will normally remain unmounted between different clinical uses, hand/eye calibration and coil calibration are required before each experiment. Today, these two steps are still separate: hand/eye calibration is performed using methods proposed by Tsai/Lenz or Floris Ernst, and then the coil calibration is carried out based on the traditional TMS experimental step. The process is complex and time-consuming, and traditional coil calibration using a handheld probe is susceptible to greater calibration error.Methods: A novel one-step calibration method has been developed to confirm hand/eye and coil calibration results by formulating a matrix equation system and estimating its solution. Hand/eye calibration and coil calibration are performed to confirm the pose relationships of the marker/end effector 'X', probe/end effector 'Y', and robot/world 'Z'. First, the coil is fixed on the end effector of the robot. During the one-step calibration process, a marker is mounted on the top of the coil and a calibration probe is fixed at the actual effective position of the coil. Next, the robot end effector is moved to a series of random positions 'A', the tracking data of marker 'B' and probe 'C' is obtained correspondingly. Then, a matrix equation system AX = ZB and AY = ZC can be acquired, and it is computed using a least-squares approach. Finally, the calibration probe is removed after calibration, while the marker remains fixed to the coil during the TMS experiment. The methods were evaluated based on simulation data and on experimental data from an optical tracking device. We compared our methods with two classical methods: the QR24 method proposed by Floris Ernst and the handheld coil calibration method.Results: The new methods outperform the QR24 method in the aspect of translational accuracy and performs similarly in the aspect of rotational accuracy, the total translational error decreased more than fifty percent. The new approach also outperforms traditional handheld coil calibration of navigated TMS systems, the total translational error decreased three- to fourfold, and the rotational error decreased six- to eightfold. Furthermore, the convergence speed is improved 16- to 27-fold for the new algorithms.Conclusion: These results suggest that the new method can be used for hand/eye and coil calibration of a robotized TMS system. Two complex steps can be simplified using a least-squares approach. [ABSTRACT FROM AUTHOR]