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.

Paraspeckle protein NONO attenuates vascular calcification by inhibiting bone morphogenetic protein 2 transcription.

Vascular calcification is a pathological process commonly associated with atherosclerosis, chronic kidney disease, and diabetes. Paraspeckle protein NONO is a multifunctional RNA/DNA binding protein involved in many nuclear biological processes but its role in vascular calcification remains unclear. Here, we observed that NONO expression was decreased in calcified arteries of mice and patients with CKD. We generated smooth muscle-specific NONO-knockout mice and established three different mouse models of vascular calcification by means of 5/6 nephrectomy, adenine diet to induce chronic kidney failure, or vitamin D injection. The knockout mice were more susceptible to the development of vascular calcification relative to control mice, as verified by an increased calcification severity and calcium deposition. Likewise, aortic rings from knockout mice showed more significant vascular calcification than those from control mice ex vivo. In vitro, NONO deficiency aggravated high phosphate-induced vascular smooth muscle cell osteogenic differentiation and apoptosis, whereas NONO overexpression had a protective effect. Mechanistically, we demonstrated that the regulation of vascular calcification by NONO was mediated by bone morphogenetic protein 2 (BMP2). NONO directly bound to the BMP2 promoter using its C-terminal region, exerting an inhibitory effect on the transcription of BMP2. Thus, our study reveals that NONO is a novel negative regulator of vascular calcification, which inhibits osteogenic differentiation of vascular smooth muscle cell and vascular calcification via negatively regulating BMP2 transcription. Hence, NONO may provide a promising target for the prevention and treatment of vascular calcification.

Association of Traditional dietary pattern with early and precocious puberty: a population-based cross-sectional study.

BACKGROUND: Precocious puberty is an endocrine disease that is diagnosed by sex, age, and Tanner stage of puberty. This study aimed to investigate the association between various dietary patterns and early or precocious puberty, especially Traditional dietary patterns, which have been rarely investigated. METHODS: A total of 4085 primary school students in grades 1-3 (6-9 years) completed individual characteristic surveys, health examinations, and food frequency questionnaires (FFQs). Physical examinations were also conducted to assess obesity and pubertal onset. Traditional, Westernized, and Protein dietary patterns were determined by factor analysis, and their associations with pubertal onset were analyzed by multiple logistic regression analysis. RESULTS: Compared to the other two patterns, children who predominant the Traditional dietary pattern were protectively associated with precocious puberty (OR = 0.72, 95% CI = 0.55, 0.94), even after adjusting the confounders (OR = 0.66, 95% CI = 0.48, 0.89). Neither the Westernized nor Protein dietary pattern demonstrated an association with pubertal onset. The Traditional dietary pattern was negatively associated with children's weight status, classified by body mass index (BMI), and was positively associated with parental education. The maternal education and the Protein dietary pattern were negatively related. CONCLUSIONS: Traditional dietary patterns were protective associated with early and precocious puberty among Chinese children. IMPACT: The Traditional dietary pattern was protective associated with early puberty or precocious puberty in children, as found in large-scale population-based public health research. Current research primarily focuses on Westernized dietary patterns, and we studied Traditional dietary patterns to further explore the influence of food on children's puberty development. We discovered that children's preference for Traditional dietary patterns is protective of pubertal development, which implies that society and parents can benefit from diet guidance to protect children's natural development during adolescence.

Diagnosis of Autism Spectrum Disorder by Dynamic Local Graph-Theory Indicators Based on Electroencephalogram.

BACKGROUND: Autism Spectrum Disorder (ASD) is a complex neurodevelopment disease characterized by impaired social and cognitive abilities. Despite its prevalence, reliable biomarkers for identifying individuals with ASD are lacking. Recent studies have suggested that alterations in the functional connectivity of the brain in ASD patients could serve as potential indicators. However, previous research focused on static functional-connectivity analysis, neglecting temporal dynamics and spatial interactions. To address this gap, our study integrated dynamic functional connectivity, local graph-theory indicators, and a feature-selection and ranking approach to identify biomarkers for ASD diagnosis. METHODS: The demographic information, as well as resting and sleeping electroencephalography (EEG) data, were collected from 20 ASD patients and 25 controls. EEG data were pre-processed and segmented into five sub-bands (Delta, Theta, Alpha-1, Alpha-2, and Beta). Functional-connection matrices were created by calculating coherence, and static-node-strength indicators were determined for each channel. A sliding-window approach, with varying widths and moving steps, was used to scan the EEG series; dynamic local graph-theory indicators were computed, including mean, standard deviation, median, inter-quartile range, kurtosis, and skewness of the node strength. This resulted in 95 features (5 sub-bands × 19 channels) for each indicator. A support-vector-machine recurrence-feature-elimination method was used to identify the most discriminative feature subset. RESULTS: The dynamic graph-theory indicators with a 3-s window width and 50% moving step achieved the highest classification performance, with an average accuracy of 95.2%. Notably, mean, median, and inter-quartile-range indicators in this condition reached 100% accuracy, with the least number of selected features. The distribution of selected features showed a preference for the frontal region and the Beta sub-band. CONCLUSIONS: A window width of 3 s and a 50% moving step emerged as optimal parameters for dynamic graph-theory analysis. Anomalies in dynamic local graph-theory indicators in the frontal lobe and Beta sub-band may serve as valuable biomarkers for diagnosing autism spectrum disorders.

Optimization of Flavonoid Extraction from Eucommia ulmoides pollen using Respond Surface Methodology and its biological activities.

Flavonoids, known for their abundance in Eucommia ulmoides pollen, possess diverse biological functions, including antioxidants, antibacterial agents, and anti-tumor properties. This study aims to establish effective parameters for flavonoid extraction from Eucommia ulmoides pollen using a microwave-assisted method, characterize the flavonoid composition of the extracted material, and explore its biological activities. Building upon the initial results from single-factor experiments, response surface methodology was employed to optimize the extraction parameters. The inhibitory effect of human breast cancer cells (MCF-7) was evaluated by CCK assay and Live/dead staining. Simultaneously, the extract's scavenging ability against DPPH free radicals and its antibacterial properties against Escherichia coli and Staphylococcus aureus were investigated. The results demonstrated that the flavonoid yield reached 3.28 g per 100 g of pollen, closely aligning with the predicted value. The IC50 for flavonoid-mediated DPPH radical scavenging was 0.04 mg/mL. The extract exhibited a robust inhibitory effect on both Escherichia coli and Staphylococcus aureus. Concurrently, the extract displayed a significant inhibitory effect on the growth and proliferation of MCF-7 cells in a dose-dependent and time-dependent manner. In addition, six kinds of flavonoids have been identified by UPLC-TOF-MS/MS technology, providing further support to the study on the anti-oxidation and anti-tumor mechanism of Eucommia ulmoides pollen extracts.

Dynamic monitoring of aboveground biomass in inner Mongolia grasslands over the past 23 Years using GEE and analysis of its driving forces.

Aboveground biomass (AGB) in grasslands directly reflects the net primary productivity, making it a sensitive indicator of grassland resource quality and ecological degradation. Accurately estimating AGB over large regions to reveal long-term AGB evolution trends remains a formidable challenge. In this study, we divided Inner Mongolia Autonomous Region (IMAR) grasslands into three study regions based on their spatial distribution of grassland types. We combined remote sensing data with ground-based sample data collected over the past 19 years from 6114 field plots using the Google Earth Engine platform. We constructed random forest (RF) and traditional regression AGB inversion models for each region and selected the best-performing model through accuracy assessment to estimate IMAR grassland AGB for the period 2000-2022. We also examined the trends in AGB changes and identified the driving forces affecting IMAR grasslands through the application of Theil-Sen estimation, Mann-Kendall trend analysis, and the Geodetector model. The main findings are as follows: (1) Compared with the univariate parametric traditional regression model, the AGB monitoring accuracy of the multivariate non-parametric RF model in the three study regions increased by 5.94%, 5.08% and 19.14%, respectively. (2) The average AGB per unit area of IMAR grasslands from 2000 to 2022 was 731.41 kg/hm2, with alpine meadow having the highest average AGB (1271.70 kg/hm2) and temperate grassland desertification having the lowest (469.06 kg/hm2). IMAR grasslands exhibited an overall increasing trend in AGB over the past 23 years (6.01 kg/hm2•yr), with the increasing trend covering 83.52% of the grassland area and the decreasing trend covering 16.48%. (3) Spatially, IMAR grassland AGB showed a gradual decline from northeast to southwest and exhibited an increasing trend with increasing longitude (45.423 kg/hm2 per degree) and latitude (71.9 kg/hm2 per degree). (4) Meteorological factors were the most significant factors affecting IMAR grassland AGB, with precipitation (five-year average q value of 0.61) being the most prominent. In the western part of IMAR, where precipitation is consistently limited throughout the year, the primary drivers of influence were human activities, with particular emphasis on the number of livestock (with a five-year average q value of 0.44). It is evident that reducing human activity disturbance and pressure in fragile grassland areas or implementing near-natural restoration measures will be beneficial for the sustainable development of grassland ecosystems. The results of this research hold substantial reference importance for the protection and restoration of grasslands, the supervision and administration of grassland resources, as well as the development of policies related to grassland management.

Quorum Sensing Is Required for the Colony Establishment of a Plant Phyllosphere Bacterium Rhodopseudomonas palustris Strain GJ-22.

The phyllosphere presents a hostile environment for many biocontrol agents; however, it is as significant as is the rhizosphere for plant health. Deploying biocontrol bacteria into the phyllosphere can efficiently suppress diseases; however, the lack of knowledge on the phyllosphere adaptive traits of biocontrol bacteria poses challenges. In this study, we demonstrated that Rhodopseudomonas palustris GJ-22 colonizes the phyllosphere by forming cell aggregates. The formation of cell aggregates required the production of exopolysaccharides (EPS), which depended on the function of the rpaI-rpaR quorum sensing (QS) mechanism, mediated by the signaling molecule p-coumaroyl-HSL (pC-HSL). The mutation of the EPS biosynthesis gene Exop1 or the signaling molecule biosynthesis gene rpaI compromised the ability of GJ-22 to tolerate reactive oxygen intermediates (ROIs), such as H2O2, in vitro and to form cell aggregates in vivo. Collectively, the results revealed that QS mediates EPS production and consequently leads to bacterial cell aggregation. IMPORTANCE Quorum sensing is used by various bacteria for coordinating the multiplication of bacterial cells in a group and for modulating the behaviors of surrounding microbial species. Host plants can benefit from this interspecies modulation, as it can disrupt the QS circuits of pathogenic bacteria. Some N-acyl homoserine lactone- (AHL-) producing bacteria that were introduced into the phyllosphere as biocontrol agents may establish AHL-based crosstalk with indigenous microbes to steer the nutritional and microecological conditions toward their own and the host plant's benefit. Here, we showed that biocontrol bacteria introduced into the phyllosphere require a functioning QS circuit to establish colonies and suppress pathogens. Furthermore, our findings provoked a broader investigation into the role of the QS circuit in beneficial microorganism-plant interactions.

Reconstruction of Water-Filled Pipe Ultrasonic Guided Wave Signals in the Distance Domain by Orthogonal Matching Pursuit Based on Dispersion and Multi-Mode.

Ultrasonic guided waves (UGWs) in water-filled pipes are subject to more severe dispersion and attenuation than vacant pipes, posing significant challenges for defect identification and localization. To this end, a novel sparse signal decomposition method called orthogonal matching pursuit based on dispersion and multi-mode (DMOMP) was proposed, which utilizes the second-order asymptotic solution of dispersion curves and the conversion characteristics of asymmetric UGWs in the defect contact stage to reconstruct the dispersive signals and converts the time-domain dispersive signals to distance-domain non-dispersive signals by dispersion compensated time-distance mapping. The synthesized simulation results indicate that DMOMP not only exhibits higher reconstruction accuracy compared to OMP, but also reveals more accurate and stable mode recognition and localization compared to DOMP, which only considers the dispersion under perturbation and noise. In addition, the UGW testing experimental results of water-filled pipes verify the effectiveness of DMOMP, the localization accuracies of three feature signals (defct 1, defct 2 and end echo) with DMOMP are 99.10%, 98.72% and 98.36%, respectively, and the average localization accuracy of DMOMP is as high as 98.73%.

Controllable Regiodivergent Alkynylation of 1,3-Bis(Boronic) Esters Activated by Distinct Organometallic Reagents.

1,3-Bis(boronic) esters can be readily synthesized from alkylBpin precursors. Selective transformations of these compounds hold the potential for late-stage functionalization of the remaining C-B bond, leading to a diverse array of molecules. Currently, there are no strategies available to address the reactivity and, more importantly, the controllable regiodivergent functionalization of 1,3-bis(boronic) esters. In this study, we have achieved controllable regiodivergent alkynylation of these molecules. The regioselectivity has been clarified based on the unique chelation patterns observed with different organometallic reagents. Remarkably, this methodology effectively addresses the low reactivity of 1,3-bis(boronic) esters and bridges the gap in radical chemistry, which typically yields only the classical products formed via stable radical intermediates. Furthermore, the compounds synthesized through this approach serve as potent building blocks for creating molecular diversity.

Dynamic of land use, landscape, and their impact on ecological quality in the northern sand-prevention belt of China.

Changes in land use and landscapes have a direct impact on the regional eco-environment. It is of great importance to understand the change pattern of land use, landscapes, and their mechanism on the ecological quality, especially ecologically fragile areas. The northern sand-prevention belt (NSPB) is an important ecologically fragile area in China, which has a large influence on the ecological security of the entire country. Based on the land use data of the NSPB in 2000, 2010, and 2018, we studied the spatio-temporal characteristics of land-use change and change in landscape patterns. The ecological quality represented by the remote sensing-based desertification index (RSDI) was calculated using satellite images. The effects of land use and landscape patterns on RSDI were analyzed by geographic detector and geographically weighted regression. Important results include the following: (1) Land-use change in the study area was high during 2000-2010 but slower in 2010-2018. Grassland was the largest land-use type in the NSPB, and varied greatly in terms of total change and spatial location. The major change was the conversion between dense and moderate grass, with 64,860 km2 of dense grass turning into moderate grass, and 48,505 km2 changing the other way. (2) Among the four landscape metrics, patch density, area-weighted mean fractal dimension, and edge density increased, whereas the aggregation index decreased, which indicated that the landscape was developing towards heterogeneity, fragmentation, complexity, and aggregation. Spatially, the landscape metrics presented a strip distribution in the east of the NSPB. (3) The effects of various land-use types on ecological quality, from high to low, were unused land, woodland, dense grass, cropland, moderate grass, built-up land, sparse grass, and waterbody. The areas where the ecological quality was greatly affected by the landscape patterns were concentrated in the agro-pastoral ecotone and the forest-steppe ecotone. The results of this study reveal the trends of land use and landscape patterns in the NSPB over 18 years and can help to understand their mechanism on ecological quality, which is of significance for the management of this area.

Monitoring residue levels and dietary risk assessment of thiamethoxam and its metabolite clothianidin for Chinese consumption of Chinese kale.

BACKGROUND: Thiamethoxam is widely used to control pests in Chinese kale, popularly consumed leafy vegetables. The potential risk to the environment and human health has aroused much public concern. Therefore, it is important to investigate the degradation behavior, residue distribution and dietary risk assessment of thiamethoxam in Chinese kale. RESULTS: A sensitive analytical method for determination of thiamethoxam and its metabolite clothianidin residue in Chinese kale was established and validated through a quick, easy, cheap, effective, rugged, and safe (QuEChERS) technique with ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). The recoveries were 85.4-101.2% for thiamethoxam and 79.5-108.1% for clothianidin, with the relative standard deviations (RSDs) of 0.9-10.2% and 1.8-6.0%, respectively. For the dissipation kinetics, the data showed that thiamethoxam in Chinese kale was degraded with the half-lives of 4.1 to 4.5 days. In the terminal residue experiments, the residues of thiamethoxam were 0.017-0.357 mg kg-1 after application 2-3 times with a preharvest interval (PHI) of 7 days under the designed dosages. The chronic and acute dietary exposure assessment risk quotient (RQ) values of thiamethoxam in Chinese kale for different Chinese consumers were 0.08-0.19% and 0.05-0.12%, respectively, and those of clothianidin were 0.01-0.04% and 0.02-0.04%, respectively, all of the RQ values were lower than 100%. CONCLUSION: Thiamethoxam in Chinese kale was rapidly degraded following first-order kinetics models. The dietary risk of thiamethoxam and clothianidin through Chinese kale was negligible to consumers. The results from this study are important reference for Chinese governments to developing criteria for the safe and rational use of thiamethoxam, setting maximum residue levels (MRLs), monitoring the quality safety of agricultural products and protecting consumer health. © 2021 Society of Chemical Industry.

Residue analysis and dietary risk assessment of tebuconazole in loquat and sugarcane after open-field application in China.

Tebuconazole is an effective but potentially carcinogenic fungicide. Tebuconazole residues in loquat and sugarcane were investigated, together with an analysis of their dietary risk. Solid-phase extraction and high-performance liquid chromatography-tandem mass spectrometry showed fortified recoveries of 87% to 98%, with standard deviations ≤ 6.4%. The tebuconazole residues were below 6.34 mg kg-1 for whole loquat and 0.80 mg kg-1 for sugarcane. Based on the final residue test, the chronic hazard index was 90.74% in whole loquat and sugarcane, while the acute hazard index ranged from 66.32% to 109.49% for loquat and 33.37% to 76.93% for sugarcane. The assessment of potential dietary risk showed that while loquats may represent an acute risk to human health, whereas sugarcane consumption was safe. A 21-day pre-harvest interval is proposed to comply with maximum residue limit regulations and the observed risks when using 430 g/L tebuconazole for treating sugarcane. These findings offer guidance for tebuconazole formulation and use.

Three-wavelength optical sensor for measuring distributed mass concentrations of aerosols from stationary sources.

Stationary source emissions of key industries, such as thermal power plants, have become the central consideration in environmental protection programs. Existing photoelectric sensors at stationary sources usually use a single wavelength laser to measure the total mass concentration of the particulate matter, bearing inherent errors due to the changing particle size distribution (PSD). However, the total mass concentration cannot comprehensively estimate the air pollution caused by the stationary sources. Therefore, it is required to measure both the mass concentration and PSD of the aerosols emitted by the stationary sources, based on which we can get a distributed mass concentration. To implement this, in this study, we designed a novel three-wavelength photoelectric sensor and tested its performance. Results showed that the prototype correctly determines the mean particle size and standard deviation of the PSDs and consequently adjusts the coefficient for measuring the mass concentration from light intensity, providing a comprehensive assessment of the pollutants.

Residue behavior, transfer and risk assessment of tolfenpyrad, dinotefuran and its metabolites during tea growing and tea brewing.

BACKGROUND: Tolfenpyrad and dinotefuran are two representative pesticides used for pest control in tea gardens. Their application may bring about a potential risk to the health of consumers. Therefore, it is essential to investigate the residue behavior, transfer and risk assessment of tolfenpyrad, dinotefuran and metabolites from tea garden to teacup. RESULTS: An effective analytical method was established and validated to simultaneously determine tolfenpyrad, dinotefuran and its metabolites (DN and UF) in tea. The average recoveries of tolfenpyrad, dinotefuran, DN and UF were in the range 72.1-106.3%, with relative standard deviations lower than 11.8%. On the basis of the proposed method, the dissipation of tolfenpyrad and dinotefuran in fresh tea leaves followed first-order kinetics models with half-lives of 4.30-7.33 days and 4.65-5.50 days, respectively. With application amounts of 112.5-168.75 g a.i. ha-1 once or twice, the terminal residues of tolfenpyrad and total dinotefuran in green tea were lower than 19.6 and 7.13 mg kg-1 , respectively, and below their corresponding maximum residue limits . The leaching rates of tolfenpyrad and total dinotefuran during the tea brewing were in the ranges 1.4-2.3% and 93.7-98.1%, respectively. CONCLUSION: Tolfenpyrad and dinotefuran in tea were easily degraded. The RQc and RQa values for tolfenpyrad were 37.6% and 5.4%, which were much higher than for dinotefuran at 24.7% and 0.84%, respectively. The data indicated that there was no significant health risk in tea for consumers at the recommended dosages. The results provide scientific data regarding the reasonable use of tolfenpyrad and dinotefuran aiming to ensure safe tea consuption. © 2021 Society of Chemical Industry.

Study on degradation behaviour, residue distribution, and dietary risk assessment of propiconazole in celery and onion under field application.

BACKGROUND: Propiconazole is widely used to control fungal diseases in field crops, including celery and onion. The potential risk to the environment and human health has aroused much public concern. Therefore, it is significant to investigate the degradation behaviour, residue distribution, and dietary risk assessment of propiconazole in celery and onion. RESULTS: A sensitive analytical method for determination of propiconazole residue in celery and onion was established and validated through high-performance liquid chromatography tandem mass spectrometry. The average recovery rate of propiconazole ranged from 85.7% to 101.8%, with a relative standard deviation of 2.1-6.3%. For the dissipation kinetics, the data showed that propiconazole in celery and onion was degraded, with half-lives of 6.1-6.2 days and 8.7-8.8 days respectively. In the terminal residue experiments, the residues of propiconazole were below 4.66 mg kg-1 in celery after application two or three times and were below 0.029 mg kg-1 in onion after application of three or four times with an interval of 14 days under the designed dosages. The chronic and acute dietary exposure assessments for propiconazole were valued by risk quotient, with all values being lower than 100%. CONCLUSION: Propiconazole in celery and onion was rapidly degraded following first-order kinetics models. The dietary risk of propiconazole through celery or onion was negligible to consumers. The study not only offers a valuable reference for reasonable usage of propiconazole on celery and onion, but also facilitates the establishment of maximum residue limits in China. © 2020 Society of Chemical Industry.

Middle School Students' Understanding of Energy in Health and Fitness.

We used mixed methods to identify middle school students' conceptions and misconceptions of energy in the domain of health and fitness. We selected a total of 24 middle schools from six school districts in a Southeastern state of the U. S. through stratified sampling. Students were first given a standardized knowledge test to establish their knowledge level membership in the domain of health and fitness. A sample of 291 students was selected from the 24 schools for semi-structured interviews on their understanding of energy sources for physical activities and consequences of energy surplus. Analysis of the interview data identified a variety of misconceptions on energy by grade and knowledge levels. Different conceptual change theories were adopted to form four themes to explain the identified misconceptions. We discussed pedagogical implications that may help address the misconceptions in and beyond the domain of health and fitness.

Structural insights into the nuclear import of the histone acetyltransferase males-absent-on-the-first by importin α1.

The histone acetyltransferase males-absent-on-the-first (MOF) acetylates the histone H4, a modification important for many biological processes, including chromatin organization, transcriptional regulation, DNA replication, recombination and repair, as well as autophagy. Depletion of MOF induces serious consequences because of the reduction of histone acetylation, such as nuclear morphological defects and cancer. Despite the critical roles of MOF in the nucleus, the structural or functional mechanisms of the nucleocytoplasmic transport of MOF remain elusive. Here, we identified novel importin α1-specific nuclear localization signals (NLSs) in the N-terminal of human MOF. The crystal structure of MOF NLSs in complex with importin α1 further revealed a unique binding mode of MOF, with two independent NLSs binding to importin α1 major and minor sites, respectively. The second NLS of MOF displays an unexpected α-helical conformation in the C-terminus, with more extensive contacts with importin α1 not limited in the minor site. Mutations of the key residues on MOF and importin α1 lead to the reduction of their interaction as well as the nuclear import of MOF, revealing an essential role of NLS2 of MOF in interacting with importin α1 minor site. Taken together, we provide structural mechanisms underlying the nucleocytoplasmic transport of MOF, which will be of great importance in understanding the functional regulation of MOF in various biological processes.

Generation and Characterization of Cytochrome P450 2J3/10 CRISPR/Cas9 Knockout Rat Model.

Cytochrome P450 2J2 (CYP2J2) enzyme attracts more attention because it not only metabolizes clinical drugs but also mediates the biotransformation of important endogenous substances and the regulation of physiologic function. Although CYP2J2 is very important, few animal models are available to study its function in vivo In particular, a CYP2J gene knockout (KO) rat model for drug metabolism and pharmacokinetics is not available. In this report, the CRISPR/Cas9 technology was used to delete rat CYP2J3/10, the orthologous genes of CYP2J2 in humans. The CYP2J3/10 KO rats were viable and fertile and showed no off-target effect. Compared with wild-type (WT) rats, the mRNA and protein expression of CYP2J3/10 in liver, small intestine, and heart of KO rats were completely absent. At the same time, CYP2J4 mRNA expression and protein expression were significantly decreased in these tissues. Further in vitro and in vivo metabolic studies of astemizole, a typical substrate of CYP2J, indicated that CYP2J was functionally inactive in KO rats. The heart function indexes of WT and KO rats were also measured and compared. The myocardial enzymes, including creatine kinase-muscle brain type (CK-MB), creatine kinase (CK), and CK-MB/CK ratio, of KO rats increased by nearly 140%, 80%, and 60%, respectively. In conclusion, this study successfully developed a new CYP2J3/10 KO rat model, which is a useful tool to study the function of CYP2J in drug metabolism and cardiovascular disease. SIGNIFICANCE STATEMENT: Human CYP2J2 is involved not only in clinical drug metabolism but also in the biotransformation of important endogenous substances. Therefore, it is very important to construct new animal models to study its function in vivo. This study successfully developed a new CYP2J knockout rat model by using CRISPR/Cas9 technology. This rat model provides a useful tool to study the role of CYP2J in drug metabolism and diseases.

Cross-polarization suppression for patch array antennas via generalized Kerker effects.

The generalized Kerker effect has recently gained an explosive progress in metamaterials, from the scattering management of particle clusters to the reflection and transmission manipulation of metalattices and metasurfaces. Various optical phenomena observed can be explained by the generalized Kerker effect. Due to the same nature of electromagnetic waves, we believe that the generalized Kerker effect can also be used in the microwave field. Inspired by this, in this letter we design a kind of patch array antenna to suppress the cross-polarization by interferences of multipoles. Using different far-field radiation phase symmetries of electromagnetic multipoles for the patch, the cross-polarization can be almost cancelled while the co-polarization be kept. A pair of 8×8 U-slot patch array antennas, working in a wide band (8.8 GHz-10.4 GHz), have been designed, fabricated and measured to verify our proposal. Simulated and measured results both agree well with the theory, showing more than 20 dB gain suppression of the cross-polarization, which indicates the universality of the generalized Kerker effect in electromagnetic waves.

Ultrawideband, Wide Scanning Stripline-Fed Tightly Coupled Array Antenna Based on Parallel-Dipole Elements.

A stripline-fed tightly coupled array antenna with compact size, large scan volume and low cross-polarization characteristics is proposed for ultrawideband (UWB) applications. Simple impedance-matching process is realized by using parallel dual dipoles. Meanwhile, the parallel symmetrical radiating structures minimize the cross-polarization field components dramatically. The mitigation of various undesired resonances is studied in detail. An infinite array is designed to achieve 3:1 bandwidth (6-18 GHz) when scanning ±60∘ in the E-/D-planes (VSWR < 2.5) and H-plane (VSWR < 3.5). The cross-polarization levels remain below -29 dB at broadside. A 16 × 16 prototype is fabricated to demonstrate the design. The measured results are consistent well with the simulated ones. The overall size of the prototype at the lowest operating frequency is 3×3×0.4λ03 (15×15×2cm3). Due to its wide bandwidth, good electronic scan performance and compact size, the proposed antenna array is a good candidate for modern wireless platforms.