Efficacy and safety of thalidomide in patients with ß-thalassemia intermedia and major.

To investigate the short-term and long-term efficacy and safety of thalidomide in the treatment of intermediate and severe ß-thalassemia. We analyzed patients with intermediate and severe ß-thalassemia treated at our hospital from February 2019 to February 2024. Patients who received treatment for more than 3 months were included. The efficacy of thalidomide was assessed by comparing changes in hemoglobin (Hb), ferritin, bilirubin, and Hb electrophoresis before and after treatment. Adverse drug reactions during treatment were also recorded. A total of 42 ß-thalassemia patients were included, with thalidomide dosages ranging from 75 to 150 mg/d. The response rates at 1, 3, and 6 months of treatment were 73.8% (31/42), 75.0% (24/32), and 94.7% (18/19), respectively. The increase in Hb levels was primarily attributed to fetal hemoglobin (HbF). After 1 month of treatment, the HbF percentage increased from a baseline of 34.04 ±â€…27.58% to 56.25 ±â€…28.40% (P < .001). At 3 and 6 months, HbF further increased to 67.21 ±â€…27.12% (P < .001) and 73.93 ±â€…22.96% (P < .001), respectively. The average duration of thalidomide treatment was 25.3 ±â€…9.2 months (range: 4-60 months), with 6 patients treated for over 60 months and 18 patients for over 48 months. Two homozygous patients who failed thalidomide treatment achieved Hb levels above 100 g/L and discontinued transfusion therapy after 3 months of hydroxyurea treatment. The most common adverse reaction was somnolence, which was mild and tolerable. Thalidomide demonstrates significant and sustained therapeutic effects in ß-thalassemia patients. The adverse reactions are mild and tolerable, allowing patients to continue treatment.

(Re)Conceptualizing Sex and Gender in Physical Education through Social Role Theory.

The line between gender and sex has become increasingly muddled in recent scientific literature, including within physical education. Tensions surrounding this topic are ever-increasing and definitions of the two are rarely consistent. For improving conceptual clarity for research, we adopted the Social Role Theory to offer spaces for researchers to explore how these two terms differ and relate by laying out a cyclical framework of biological, sociological, and psychological components. Herein, we discuss the origins of the binary sex construct, anatomical brain/ cognition differences, and sex/gender role implications for education and physical education. In this conceptual paper, we confront the controversial topic in a content area that continues to be masculine-oriented with the purpose to conceptualize sex/gender in physical education research through clarifying the evolutionary bio-social spectrum. Offering a reconceptualization of gender as a multi-dimensional construct in physical education could inspire further curricular reform for the content to be more inclusive of all participants, learnable by all students regardless of sex and gender, and beneficial both mentally and physically to all learners.

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.

Retraction Notice to: circFMN2 Sponges miR-1238 to Promote the Expression of LIM-Homeobox Gene 2 in Prostate Cancer Cells.

[This retracts the article DOI: 10.1016/j.omtn.2020.05.008.].

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.

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.

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.

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.

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.

A Place-Based Conceptual Model (PBCM) of Neotricula aperta/Schistosoma mekongi habitat before and after dam construction in the Lower Mekong River.

In 1971, scientists from Mahidol University in Thailand and the Smithsonian Institution in the USA formed a research team to study a new species of Schistosoma in the Mekong River in Thailand and Laos. The studies, completed during 1971-1973, prior to the construction of any dams or restrictions to the natural flow regime of the Mekong River, provide a unique description of the natural ecological state of the river that can serve as a baseline for current research. The natural transmission of Schistosoma japonicum, Mekong Strain, was first reported on Khong Island, Laos in 1973 using sentinel mice. The first detailed description of the habitat ecology of the snail vector Neotricula aperta was done on-site in 1971 simultaneously with that research and is unique in providing the only description of the river shoreline habitat before any dams were built and any alteration of the natural flow regime was in place. Aggregating current information in a Place-Based Conceptual Model (PBCM) as an organizing template, along with current habitat models that combine ecological data with e-flows, can be developed and used as a tool to predict suitable habitats for snails. The natural flow regime of the Mekong River prior to any impoundments is described with current updates on the potential impacts of climate change and dams with flow-related snail habitat characteristics, including sediment drift and water quality. The application of the PBCM to describe and compare descriptive information on current and potential future N. aperta/S. mekongi habitat is discussed.

A meta-analysis of the value of MRI-based VBQ scores for evaluating osteoporosis.

Objective: Osteoporosis is the most common skeletal disease in humans. Early onset of osteoporosis is usually asymptomatic, so early diagnosis is critical. The purpose of this study was to analyze the value of MRI-based VBQ scores for evaluating osteoporosis. Methods: We searched PubMed, Embase, the Cochrane Library databases, Web of Science, and some Chinese electronic databases for published articles and the ClinicalTrials.gov site for completed but unpublished studies on evaluating the value of MRI-based VBQ scores for evaluating osteoporosis. We calculated the summarized sensitivity, specificity, the ROC curve (AUC) values and their 95% confidence intervals (CIs) using MetaDiSc 1.4 software and STATA. Results: Our study included 8 studies involving 999 patients of which 660 patients were diagnosed with osteopenia/osteoporosis, and 339 patients were identified as having normal BMD. The pooled sensitivity was 0.809 (95% CI, 0.777-0.838, I2 = 78.8%), the pooled specificity was 0.640 (95% CI, 0.587-0.691, I2 = 85.9%), and the pooled AUC was 0.8375. Conclusion: MRI-based VBQ scores provided high sensitivity and moderate specificity in detecting osteoporosis. Opportunistic use of VBQ scores could be considered, e.g. before lumbar spine surgery. Prospero registration number: CRD42022377024.

Performance of fish sludge solubilization and phototrophic bioconversion by purple phototrophic bacteria for nutrient recovery in aquaponic system.

Nutrient recovery from fish sludge in aquaponics is crucial to improve the economic output of a system sustainably and hygienically. Currently, fish sludge is treated using conventional anaerobic and aerobic mineralization, which does not allow the recovery of valuable nutrients in fish wastes. In this study, a two-stage approach (named as solubilization process and phototrophic bioconversion) is proposed to convert fish sludge into mineral nutrients and biomass nutrients using purple phototrophic bacteria (PPB), thereby promoting the growth of plants and fish simultaneously in aquaponics. Anaerobic and aerobic solubilization methods are tested to pretreat the fish sludge, generating substrates for PPB. Anaerobic solubilization yields 2.1 times more soluble chemical oxygen demand (SCOD) and 3.7 times more total volatile fatty acid (t-VFA) from fish sludge compared with aerobic solubilization. The anaerobic solubilization effluent indicates a CODt-VFA/SCOD of 60% and a VFA comprising 13.3% acetate and 49.0% propionate for PPB. The phototrophic bioconversion using anaerobic solubilization effluent under the light-anaerobic condition results in the highest biomass yield (0.94 g CODbiomass/g CODremoved) and the highest PPB dominance (Ectothiorhodospira, 58.7%). The anaerobic solubilization and light-anaerobic phototrophic bioconversion achieves 54.1% of carbon recovery efficiency (CRE) (in terms of COD), as well as 44.8% and 91.3% of nutrient recovery efficiency (NRE) for N and P. A novel multiloop aquaponic system combined with PPB-based nutrient recovery is proposed for the reuse of mineral nutrients and PPB biomass generated from fish sludge.

Post-translational modifications in stress granule and their implications in neurodegenerative diseases.

Stress granules (SGs) arise as formations of mRNAs and proteins in response to translation initiation inhibition during stress. These dynamic compartments adopt a fluidic nature through liquid-liquid phase separation (LLPS), exhibiting a composition subject to constant change within cellular contexts. Research has unveiled an array of post-translational modifications (PTMs) occurring on SG proteins, intricately orchestrating SG dynamics. In the realm of neurodegenerative diseases, pathological mutant proteins congregate into insoluble aggregates alongside numerous SG proteins, manifesting resilience against disassembly. Specific PTMs conspicuously label these aggregates, designating them for subsequent degradation. The strategic manipulation of aberrant SGs via PTMs emerges as a promising avenue for therapeutic intervention. This review discerns recent strides in comprehending the impact of PTMs on LLPS behavior and the assembly/disassembly kinetics of SGs. By delving into the roles of PTMs in governing SG dynamics, we augment our cognizance of the molecular underpinnings of neurodegeneration. Furthermore, we offer invaluable insights into potential targets for therapeutic intervention in neurodegenerative afflictions, encompassing conditions like amyotrophic lateral sclerosis and frontotemporal dementia.

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.

Role of nuclear receptors NlHR3 and NlFTZ-F1 in regulating molting and reproduction in Nilaparvata lugens (stål).

The nuclear receptors HR3 and FTZ-F1 are highly conserved and function to regulate molting and reproduction in both hemimetabolous and holometabolous insects. However, their roles in Nilaparvata lugens are largely unknown. In the present study, we discover that NlHR3 and NlFTZ-F1 are activated in the nymph stages by ecdysone signaling. Transcription disruption of NlHR3 and NlFTZ-F1 expression prevents nymph ecdysis and metamorphosis, which leads to abnormal appearance, malformed ovaries, and lethal phenotypes. In addition, we demonstrate that NlHR3 and NlFTZ-F1 regulate molting and reproduction by interacting with the intrinsic 20E and JH signaling pathways. Our work offers a deep insight into the action mechanisms of HR3 and FTZ-F1 in insects. Moreover, NlHR3 and NlFTZ-F1 could properly be exploited as potential target genes for developing RNAi-based pesticides to control N. lugens.

Bound states in the continuum based on the total internal reflection of Bloch waves.

A photonic-crystal slab can support bound states in the continuum (BICs) that have infinite lifetimes but are embedded into the continuous spectrum of optical modes in free space. The formation of BICs requires a total internal reflection (TIR) condition at both interfaces between the slab and the free space. Here, we show that the TIR of Bloch waves can be directly obtained based on the generalized Fresnel equations proposed. If each of these Bloch waves picks up a phase with integer multiples of 2π for traveling a round trip, light can be perfectly guided in the slab, namely forming a BIC. A BIC solver with low computational complexity and fast convergence speed is developed, which can also work efficiently at high frequencies beyond the diffraction limit where multiple radiation channels exist. Two examples of multi-channel BICs are shown and their topological nature in momentum space is also revealed. Both can be attributed to the coincidence of the topological charges of far-field radiations from different radiation channels. The concept of the generalized TIR and the TIR-based BIC solver developed offer highly effective approaches for explorations of BICs that could have many potential applications in guided-wave optics and enhanced light-matter interactions.

Cognitive Load and Energy Balance Knowledge in High-School Physical Education.

Purpose: Guided by the cognitive load theory, the purpose of this study was to determine the impacts of cognitive load and school socioeconomic status-related environmental factors on ninth-graders' energy-balanced living knowledge gain. Methods: A stratified random sample of high-school students (N = 150) participated in this study. Data were collected on students' knowledge gain, cognitive load, free and reduced-price meal rates, and student-to-teacher ratio. Results: The path analysis results revealed that the reasoning learning tasks had direct significant effects on students' knowledge gain (ßi-Diet and i-Exercise = 0.34, p < .01). The free and reduced-price meal rates and student-to-teacher ratio did not have significant effects on students' knowledge gain (p > .05). Discussion: These findings advance our understanding of the role cognitive learning tasks play in enhancing student learning in the subjects of energy-balanced knowledge and healthy lifestyle.

The expectancy-value theory: A meta-analysis of its application in physical education.

BACKGROUND: The purpose of motivating students is to enhance their learning achievement. The expectancy-value theory (EVT) has demonstrated its efficacy in motivating students in classrooms and in gymnasia. Understanding student motivation in physical education is needed. This meta-analysis review aimed to reveal the determinants and functions of EVT by evaluating the evidence in physical education research. METHODS: We followed the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines to identify and meta-analyze the current research literature published from January 2010 to December 2020 by generating and analyzing the effect sizes from the studies. RESULTS: A total of 31 studies were included. The results show that social support, motivation of teachers and peers, and positive class climate can predict student EVT motivation. EVT motivation predicts student learning behaviors, situational interests, fitness performance, health behavior function, out-of-school physical activity, and physical skill development. CONCLUSION: EVT motivation could facilitate learning behaviors and situational interest development in the gymnasium. It might lead to fitness enhancement, health behavior change, out-of-school physical activity participation, and physical skill development. Fostering a learning environment with a mastery-centered and/or student autonomy approach where students perceived success and the task values can enhance and maximize student EVT motivation and learning achievement.

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.