Models of sepsis-induced acute kidney injury.

Sepsis-induced acute kidney injury (S-AKI) is one of the most serious life-threatening complications of sepsis. The pathogenesis of S-AKI is complex and there is no effective specific treatment. Therefore, it is crucial to choose suitable preclinical models that are highly similar to human S-AKI to study the pathogenesis and drug treatment. In this review, we summarized recent advances in the development models of S-AKI, providing reference for the reasonable selection of experimental models as basic research and drug development of S-AKI.

Epidural analgesia during surgery and its relation to postoperative myocardial infarction: meta-analysis.

Introduction: Epidural analgesia has been studied for its potential advantages after surgery in a number of randomized clinical trials, with most finding improvements in pain and secondary endpoints like the incidence of postoperative complications. Aim: To assess the relationship between use of epidural analgesia and adverse cardiac outcomes expressed by myocardial infarction (MI). Material and methods: Fifty-three studies were recruited to quantify the influence of different surgical-related analgesic methods on clinical parameters (mortality and adverse events). The results of these trials were analysed using a random effects model, which was then used to calculate the mean difference (MD) with 95 per cent confidence intervals (CIs). Results: Epidural analgesia resulted in preferred cardiac outcomes compared with traditional analgesia. These findings were supported by significantly lower MI events for the epidural analgesia group as follows: p = 0.005, p = 0,007, and p = 0.03 for the total number of included studies, studies with high risk of bias, and studies with low risk of bias, respectively. Studies with intermediate risk showed a non-significant difference between both groups (p = 0.7). Conclusions: Epidural analgesia has a significant protective cardiac effect through the reduction of postoperative MI events among surgery subjects.

Screening of active components in Astragalus mongholicus Bunge and Panax notoginseng formula for anti-fibrosis in CKD: nobiletin inhibits Lgals1/PI3K/AKT signaling to improve renal fibrosis.

The Astragalus mongholicus Bunge and Panax notoginseng formula (A&P) has been clinically shown to effectively slow down the progression of chronic kidney disease (CKD) and has demonstrated significant anti-fibrosis effects in experimental CKD model. However, the specific active ingredients and underlying mechanism are still unclear. The active ingredients of A&P were analyzed by Ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-HR-MS). A mouse model of CKD was constructed by 5/6 nephrectomy. Renal function was assessed by creatinine and urea nitrogen. Real-time PCR and Western Blot were performed to detect the mRNA and protein changes in kidney and cells. An in vitro fibrotic cell model was constructed by TGF-ß induction in TCMK-1 cells. The results showed that thirteen active ingredients of A&P were identified by UPLC-HR-MS, nine of which were identified by analysis with standards, among which the relative percentage of NOB was high. We found that NOB treatment significantly improved renal function, pathological damage and reduced the expression level of fibrotic factors in CKD mice. The results also demonstrated that Lgals1 was overexpressed in the interstitial kidney of CKD mice, and NOB treatment significantly reduced its expression level, while inhibiting PI3K and AKT phosphorylation. Interestingly, overexpression of Lgals1 significantly increased fibrosis in TCMK1 cells and upregulated the activity of PI3K and AKT, which were strongly inhibited by NOB treatment. NOB is one of the main active components of A&P. The molecular mechanism by which NOB ameliorates renal fibrosis in CKD may be through the inhibition of Lgals1/PI3K/AKT signaling pathway.

Impaired Reactive Control But Preserved Proactive Control in Hyperactive Children.

OBJECTIVE: To examine the manifestation of cognitive control deficit of children with different levels of hyperactivity, an "at risk" dimension for ADHD. METHOD: A group of children with high hyperactivity (N = 40) and another group of children with low levels of hyperactivity (N = 38) performed a modified stop-signal anticipation task, a revised Go/NoGo task, and the AX-continuous performance test (AX-CPT). RESULTS: Children with higher levels of hyperactivity displayed: (1) significantly prolonged stop signal reaction time (SSRT) in the modified stop-signal anticipation task; (2) no notable differences in commission errors in the revised Go/NoGo task; (3) increased reaction time (RT) in stop-signal task and Go/NoGo task with increased probabilities of stop or NoGo signal; and (4) positive proactive behavioral index scores in AX-CPT. CONCLUSION: The results suggested that children with heightened hyperactivity exhibited impaired reactive control, especially for responses already underway, but preserved proactive control. Further studies concerning these children are warranted.

A Platform for the Synthesis of Diverse Phosphonyl and Thiofunctionalized Sulfoxonium Ylides.

A practical strategy for the construction of diverse phosphonyl and thiofunctionalized sulfoxonium ylides via controllable monofunctionalization of hybrid I(III)/S(VI) ylides is presented. This process allows efficient P-H insertion of I(III)/S(VI) ylides under Cu catalysis, enabling the synthesis of phosphonyl sulfoxonium ylides, whereas reaction with sulfur-containing reagents including AgSCF3, KSC(S)OR, and KSCN under mild conditions resulted in α-trifluoromethylthiolation, dithiocarbanation, and thiocyanation of sulfoxonium ylides accordingly. Of note, wide substrate compatibility (108 examples), excellent efficiency (up to 99% yield), gram-scale experiments, and various product derivatizations highlight the synthetic utility of this protocol.

Site-Directed Electrochemical Grafting for Amplified Detection of Antibody Pharmaceuticals.

Antibody pharmaceuticals have become the most popular immunotherapeutic drugs and are often administered with low serum drug dosages. Hence, the development of a highly sensitive method for the quantitative assay of antibody levels is of great importance to individualized therapy. On the basis of the dual signal amplification by the glycan-initiated site-directed electrochemical grafting of polymer chains (glyGPC), we report herein a novel strategy for the amplified electrochemical detection of antibody pharmaceuticals. The target of interest was affinity captured by a DNA aptamer ligand, and then the glycans of antibody pharmaceuticals were decorated with the alkyl halide initiators (AHIs) via boronate cross-linking, followed by the electrochemical grafting of the ferrocenyl polymer chains from the glycans of antibody pharmaceuticals through the electrochemically controlled atom transfer radical polymerization (eATRP). As the glycans can be decorated with multiple AHIs and the grafted polymer chains are composed of tens to hundreds of electroactive tags, the glyGPC-based strategy permits the dually amplified electrochemical detection of antibody pharmaceuticals. In the presence of trastuzumab (Herceptin) as the target, the glyGPC-based strategy achieved a detection limit of 71.5 pg/mL. Moreover, the developed method is highly selective, and the results of the quantitative assay of trastuzumab levels in human serum are satisfactory. Owing to its uncomplicated operation and cost-effectiveness, the glyGPC-based strategy shows great promise in the amplified electrochemical detection of antibody pharmaceuticals.

Systematic evaluation and meta-analysis of the prognosis of down-staging human papillomavirus (HPV) positive oropharyngeal squamous cell carcinoma using cetuximab combined with radiotherapy instead of cisplatin combined with radiotherapy.

Objective: To evaluate the efficacy and safety of cetuximab instead of cisplatin in combination with downstaging radiotherapy for papillomavirus (HPV) positive oropharyngeal squamous cell carcinoma (HPV+ OPSCC). Design: Meta-analysis and systematic evaluation. Data sources: The PubMed, Embase, Web of Science, and Cochrane library databases were searched up to June 8, 2023, as well as Clinicaltrials.gov Clinical Trials Registry, China Knowledge Network, Wanfang Data Knowledge Service Platform, and Wiprojournal.com. Eligibility criteria for selecting studies: Randomized controlled trials reporting results of standard regimens of cetuximab + radiotherapy vs cisplatin + radiotherapy in treating HPV+ OPSCC were included. The primary outcomes of interest were overall survival (OS), progression-free survival (PFS), local regional failure rate (LRF), distant metastasis rate (DM), and adverse events (AE). Data extraction and synthesis: Two reviewers independently extracted data and assessed the risk of bias of the included studies. The HR and its 95% CI were used as the effect analysis statistic for survival analysis, while the OR and its 95% CI were used as the effect analysis statistic for dichotomous variables. These statistics were extracted by the reviewers and aggregated using a fixed-effects model to synthesise the data. Results: A total of 874 relevant papers were obtained from the initial search, and five papers that met the inclusion criteria were included; a total of 1,617 patients with HPV+ OPSCC were enrolled in these studies. Meta-analysis showed that OS and PFS were significantly shorter in the cetuximab + radiotherapy group of patients with HPV+ OPSCC compared with those in the conventional cisplatin + radiotherapy group (HR = 2.10, 95% CI [1.39-3.15], P = 0.0004; HR = 1.79, 95% CI [1.40-2.29], P < 0.0001); LRF and DM were significantly increased (HR = 2.22, 95% CI [1.58-3.11], P < 0.0001; HR = 1.66, 95% CI [1.07-2.58], P = 0.02), but there was no significant difference in overall grade 3 to 4, acute and late AE overall (OR = 0.86, 95% CI [0.65-1.13], P = 0.28). Conclusions: Cisplatin + radiotherapy remains the standard treatment for HPV+ OPSCC. According to the 7th edition AJCC/UICC criteria, low-risk HPV+ OPSCC patients with a smoking history of ≤ 10 packs/year and non-pharyngeal tumors not involved in lymphatic metastasis had similar survival outcomes with cetuximab/cisplatin + radiotherapy. However, further clinical trials are necessary to determine whether cetuximab + radiotherapy can replace cisplatin + radiotherapy for degraded treatment in individuals who meet the aforementioned characteristics, particularly those with platinum drug allergies. Prospero registration number: CRD42023445619.

Clinical efficacy of tumor organoid-guided cancer therapy for locally advanced unresectable or metastatic breast cancer.

Patient-derived organoids (PDOs) may facilitate treatment selection. This retrospective cohort study evaluated the feasibility and clinical benefit of using PDOs to guide personalized treatment in metastatic breast cancer (MBC). Patients diagnosed with MBC were recruited between January 2019 and August 2022. PDOs were established and the efficacy of customized drug panels was determined by measuring cell mortality after drug exposure. Patients receiving organoid-guided treatment (OGT) were matched 1:2 by nearest neighbor propensity scores with patients receiving treatment of physician's choice (TPC). The primary outcome was progression-free survival. Secondary outcomes included objective response rate and disease control rate. Targeted gene sequencing and pathway enrichment analysis were performed. Forty-six PDOs (46 of 51, 90.2%) were generated from 45 MBC patients. PDO drug screening showed an accuracy of 78.4% (95% CI 64.9%-91.9%) in predicting clinical responses. Thirty-six OGT patients were matched to 69 TPC patients. OGT was associated with prolonged median progression-free survival (11.0 months vs. 5.0 months; hazard ratio 0.53 [95% CI 0.33-0.85]; p = .01) and improved disease control (88.9% vs. 63.8%; odd ratio 4.26 [1.44-18.62]) compared with TPC. The objective response rate of both groups was similar. Pathway enrichment analysis in hormone receptor-positive, human epidermal growth factor receptor 2-negative patients demonstrated differentially modulated pathways implicated in DNA repair and transcriptional regulation in those with reduced response to capecitabine/gemcitabine, and pathways associated with cell cycle regulation in those with reduced response to palbociclib. Our study shows that PDO-based functional precision medicine is a feasible and effective strategy for MBC treatment optimization and customization.

Diminishing Self-Discharge of High-Loading Li-S Batteries with Oxygen-Rich Biomass Carbon Interlayers.

Lithium-sulfur batteries (Li-S) have possessed gratifying development in the past decade due to their high theoretical energy density. However, the severe polysulfide shuttling provokes undesirable self-discharge effect, leading to low energy efficiency in Li-S batteries. Herein, an interlayer composed of oxygen-rich carbon nanosheets (OCN) derived from bagasse is elaborated to suppress the shuttle effect and reduce the resultant self-discharge effect. The OCN interlayer is able to physically block the shuttling behavior of polysulfides and its oxygen-rich functional groups can strongly interact with polysulfides via O-S bonds to chemically immobilize mobile polysulfides. The self-discharge test for seven days further shows that the self-discahrge rate is diminished by impressive 93 %. As a result, Li-S batteries with the OCN interlayer achieve an ultrahigh discharge specific capacity of 710 mAh g-1 at a high mass loading of 7.18 mg. The work provides a facile method for designing functional interlayers and opens a new avenue for realizing Li-S batteries with high energy efficiency.

Impact of prior SARS-CoV-2 infection on college students' hesitancy to receive additional COVID-19 vaccine booster doses: A study from Taizhou, China.

Purpose: This study aimed to examine the impact of a history of SARS-CoV-2 infection on the hesitancy of college students to receive additional COVID-19 vaccine booster doses. Methods: A population-based self-administered online survey was conducted in July 2024 in Taizhou, China. A total of 792 respondents were included in this study. Logistic regression was conducted to identify factors associated with college students' hesitation to receive booster doses of the COVID-19 vaccine. Results: Of 792 respondents, 32.2 % hesitated to receive additional doses of the COVID-19 vaccine booster. Furthermore, 23.5 % of the respondents reported an increase in hesitancy to receiving additional COVID-19 vaccine booster doses compared to before they were infected with SARS-CoV-2. In the regression analyses, college students who had a secondary infection were more hesitant to receive additional COVID-19 vaccine booster doses (OR = 0.481, 95 % CI: (0.299-0.774), P = 0.003). Moreover, students with secondary infections who were male (OR = 0.417, 95 % CI: 0.221-0.784, P = 0.007), with lower than a bachelor's degree (OR = 0.471, 95 % CI: 0.272-0.815, P = 0.007), in non-medical majors (OR = 0.460, 95 % CI: 0.248-0.856, P = 0.014), and sophomores or below (OR = 0.483, 95 % CI: 0.286-0.817, P = 0.007) were more hesitant to receive additional COVID-19 vaccine booster doses. Conclusion: A history of SARS-CoV-2 infection affects college students' hesitation to receive additional COVID-19 vaccine booster doses, which was higher in those who experienced secondary infections.

VX-509 attenuates the stemness characteristics of colorectal cancer stem-like cells by regulating the epithelial-mesenchymal transition through Nodal/Smad2/3 signaling.

BACKGROUND: Colorectal cancer stem cells (CCSCs) are heterogeneous cells that can self-renew and undergo multidirectional differentiation in colorectal cancer (CRC) patients. CCSCs are generally accepted to be important sources of CRC and are responsible for the progression, metastasis, and therapeutic resistance of CRC. Therefore, targeting this specific subpopulation has been recognized as a promising strategy for overcoming CRC. AIM: To investigate the effect of VX-509 on CCSCs and elucidate the underlying mechanism. METHODS: CCSCs were enriched from CRC cell lines by in conditioned serum-free medium. Western blot, Aldefluor, transwell and tumorigenesis assays were performed to verify the phenotypic characteristics of the CCSCs. The anticancer efficacy of VX-509 was assessed in HCT116 CCSCs and HT29 CCSCs by performing cell viability analysis, colony formation, sphere formation, flow cytometry, and western blotting assessments in vitro and tumor growth, immunohistochemistry and immunofluorescence assessments in vivo. RESULTS: Compared with parental cells, sphere cells derived from HCT116 and HT29 cells presented increased expression of stem cell transcription factors and stem cell markers and were more potent at promoting migration and tumorigenesis, demonstrating that the CRC sphere cells displayed CSC features. VX-509 inhibited the tumor malignant biological behavior of CRC-stem-like cells, as indicated by their proliferation, migration and clonality in vitro, and suppressed the tumor of CCSC-derived xenograft tumors in vivo. Besides, VX-509 suppressed the CSC characteristics of CRC-stem-like cells and inhibited the progression of epithelial-mesenchymal transition (EMT) signaling in vitro. Nodal was identified as the regulatory factor of VX-509 on CRC stem-like cells through analyses of differentially expressed genes and CSC-related database information. VX-509 markedly downregulated the expression of Nodal and its downstream phosphorylated Smad2/3 to inhibit EMT progression. Moreover, VX-509 reversed the dedifferentiation of CCSCs and inhibited the progression of EMT induced by Nodal overexpression. CONCLUSION: VX-509 prevents the EMT process in CCSCs by inhibiting the transcription and protein expression of Nodal, and inhibits the dedifferentiated self-renewal of CCSCs.

Boronate crosslinking-based ratiometric electrochemical assay of glycated albumin.

As a product of nonenzymatic glycation, glycated albumin (GA) is a promising serum marker for the short-term glycemic monitoring in patients with diabetes. On the basis of the boronate crosslinking (BCL)-enabled direct labeling of ferrocene (Fc) tags to the nonenzymatically glycated (NEG) sites, we report herein a novel aptamer-based ratiometric electrochemical (apt-REC) platform for the point-of-care (POC) assay of GA. This apt-REC platform is based on the recognition of GA proteins by the methylene blue (MB)-modified aptamer receptors and the labeling of the Fc tags to the NEG sites via the BCL. Using MB as the reference tag and Fc as the quantification tag, the ratio of the oxidation currents (i.e., IFc/IMB) can serve as the yardstick for the ratiometric assay of GA. Due to the presence of tens of the NEG sites, each GA protein can be labeled with tens of quantification tags, permitting the amplified assay in a simple, time-saving, and low-cost manner. The ratiometric signal exhibited a good linear response over the range from 0.1 to 100 µg/mL, with a detection limit of 45.5 ng/mL. In addition to the superior reproducibility and robustness, this apt-REC platform is highly selective (capable of discriminating GA against human serum albumin (HSA)) and applicable to GA assay in serum samples. Due to its low cost, high reproducibility and robustness, simple operation, and high sensitivity and selectivity, this apt-REC platform holds great promise in the POC assay of GA for diabetes management.

The Relationship between Socioeconomic Status and Academic Achievement is Mediated and Moderated by Executive Functions.

Executive function is an underlying mechanism linking family socioeconomic status (SES) and academic achievement. Previous studies mainly investigated either the mediating or moderating role of executive function within this relationship, which either overlook the individual differences that are independent of the environment or neglect the influence of the environment on shaping personal factors. To avoid a piecemeal approach to theory, the current study aimed to test the mediating and moderating roles of executive function in a single analytic model. Two hundred and thirty-six Chinese fifth graders (Mage = 10.70 years, SD = 0.49, range = 10.23-11.75 years, and 40.30% girls) were recruited. Their executive function performance was measured using eight different tasks, and their Chinese literacy skills and mathematics achievement were assessed by routine school evaluations. One year after the initial assessment, children's academic achievements were evaluated again. Results demonstrated that parental SES positively predicted children's academic achievement when controlling for prior academic achievement, and children's executive function mediated this relationship. Also, executive function moderated the association between SES and academic achievement in that, the negative predictive effect of low SES on academic achievement was only significant for children with lower levels of executive function, which is not shown in children with higher levels of executive function. By demonstrating the dual roles of executive function in the SES-achievement link, this work provides evidence for supporting the optimal development of children from diverse socioeconomic backgrounds and emphasizes the significance of developing individualized intervention strategies on executive function to mitigate the negative effect of low SES on children's academic achievement.

CCT2 prevented ß-catenin proteasomal degradation to sustain cancer stem cell traits and promote tumor progression in epithelial ovarian cancer.

BACKGROUND: Epithelial ovarian cancer (EOC) is featured by rapid progression and dismal outcomes clinically. Chaperonin Containing TCP1 Subunit 2 (CCT2) was identified as a crucial regulator for tumor progression, however, its exact role in EOC remained largely unknown. METHODS: CCT2 expression and prognostic value in EOC samples were assessed according to TCGA dataset. Proliferation and mobility potentials were assessed by CCK8, colony-formation, wound healing, and Transwell assays. Cancer stem cell (CSC) traits were evaluated by RT-PCR, WB assays, sphere-forming assay and chemoresistance analysis. Bioinformatic analysis, co-IP assays and ubiquitin assays were performed to explore the mechanisms of CCT2 on EOC cells. RESULTS: CCT2 highly expressed in EOC tissues and predicted poor prognosis of EOC patients by TCGA analysis. Silencing CCT2 significantly restrained cell proliferation, migration, and invasion. Moreover, CCT2 could effectively trigger epithelial-mesenchymal transition to confer extensive invasion potentials to EOC cells, Importantly, CCT2 positively correlated with CSC markers in EOC, and CCT2 knockdown impaired CSC traits and sensitize EOC cells to conventional chemotherapy regimens. Contrarily, overexpressing CCT2 achieved opposite results. Mechanistically, CCT2 exerted its pro-oncogene function by triggering Wnt/ß-catenin signaling. Specifically, CCT2 could recruit HSP105-PP2A complex, a well-established dephosphorylation complex, to ß-catenin via direct physical interaction to prevent phosphorylation-induced proteasomal degradation of ß-catenin, resulting in intracellular accumulation of active ß-catenin and increased signaling activity. CONCLUSIONS: CCT2 was a novel promotor for EOC progression and a crucial sustainer for CSC traits mainly by preventing ß-catenin degradation. Targeting CCT2 may represent a promising therapeutic strategy for EOC.

Targeted mutagenesis of BnTTG1 homologues generated yellow-seeded rapeseed with increased oil content and seed germination under abiotic stress.

Yellow seed is one desirable trait with great potential to improve seed oil quality and yield. The present study surveys the redundant role of BnTTG1 genes in the proanthocyanidins (PA) biosynthesis, oil content and abiotic stress resistance. Stable yellow seed mutants were generated after mutating BnTTG1 by CRISPR/Cas9 genome editing system. Yellow seed phenotype could be obtained only when both functional homologues of BnTTG1 were simultaneously knocked out. Homozygous mutants of BnTTG1 homologues showed decreased thickness and PA accumulation in seed coat. Transcriptome and qRT-PCR analysis indicated that BnTTG1 mutation inhibited the expression of genes involved in phenylpropanoid and flavonoid biosynthetic pathways. Increased seed oil content and alteration of fatty acid (FA) composition were observed in homozygous mutants of BnTTG1 with enriched expression of genes involved in FA biosynthesis pathway. In addition, target mutation of BnTTG1 accelerated seed germination rate under salt and cold stresses. Enhanced seed germination capacity in BnTTG1 mutants was correlated with the change of expression level of ABA responsive genes. Overall, this study elucidated the redundant role of BnTTG1 in regulating seed coat color and established an efficient approach for generating yellow-seeded oilseed rape genetic resources with increase oil content, modified FA composition and resistance to multiple abiotic stresses.

Genomics of predictive radiation mutagenesis in oilseed rape: modifying seed oil composition.

Rapeseed is a crop of global importance but there is a need to broaden the genetic diversity available to address breeding objectives. Radiation mutagenesis, supported by genomics, has the potential to supersede genome editing for both gene knockout and copy number increase, but detailed knowledge of the molecular outcomes of radiation treatment is lacking. To address this, we produced a genome re-sequenced panel of 1133 M2 generation rapeseed plants and analysed large-scale deletions, single nucleotide variants and small insertion-deletion variants affecting gene open reading frames. We show that high radiation doses (2000 Gy) are tolerated, gamma radiation and fast neutron radiation have similar impacts and that segments deleted from the genomes of some plants are inherited as additional copies by their siblings, enabling gene dosage decrease. Of relevance for species with larger genomes, we showed that these large-scale impacts can also be detected using transcriptome re-sequencing. To test the utility of the approach for predictive alteration of oil fatty acid composition, we produced lines with both decreased and increased copy numbers of Bna.FAE1 and confirmed the anticipated impacts on erucic acid content. We detected and tested a 21-base deletion expected to abolish function of Bna.FAD2.A5, for which we confirmed the predicted reduction in seed oil polyunsaturated fatty acid content. Our improved understanding of the molecular effects of radiation mutagenesis will underpin genomics-led approaches to more efficient introduction of novel genetic variation into the breeding of this crop and provides an exemplar for the predictive improvement of other crops.

The relation between effortful control and executive function training in preschoolers.

In recent years, the question of whether executive function (EF) is malleable has been widely documented. Despite using the same training tasks, transfer effects remain uncertain. Researchers suggested that the inconsistency might be attributed to individual differences in temperamental traits. In the current study, we investigated how effortful control, a temperamental trait, would affect EF training outcomes in children. Based on parent rating, 79 6-year-old preschoolers were identified as having higher or lower effort control and were assigned to three conditions: working memory (WM) training, inhibitory control (IC) training, and a business-as-usual control group. Children completed assessments at baseline, 1 week after intervention (posttest), and 3 months after intervention (follow-up). As compared with the control group, the WM and IC training groups showed improvement in both trained tasks and nontrained measures. At baseline, children with higher effortful control scores showed greater WM capacity and better IC. Furthermore, effortful control was positively correlated with training gain in both training groups, with children with higher effortful control benefitting more through training. In the WM training group, effortful control was positively correlated with near transfer on WM outcomes both immediately and longitudinally. At posttest, the WM and IC training groups showed a positive correlation between effortful control and fluid intelligence performance. Our results underscore the importance of individual differences in training benefits, in particular the role of effortful control, and further illustrate the potential avenues for designing more effective individualized cognitive training programs to foster learning and optimize children's development.

Establishment of new convenient two-line system for hybrid production by targeting mutation of OPR3 in allopolyploid Brassica napus.

The two-line pollination control system, which usually depends on the utilization of thermosensitive or photoperiod genic male-sterile lines, has been widely used in various crops. However, this system is susceptible to instability issues caused by uncontrollable weather fluctuations. A stable and handy two-line pollination control system is highly desirable in many crop species for heterosis exploitation. Oxophytodienoic acid reductase 3 (OPR3) was proven to be involved in jasmonate biosynthesis. In the present study, CRISPR/Cas9 (Clustered Regularly Interspaced Short Palindromic Repeat) was utilized to mutate two OPR3 homologs in Brassica napus. After two OPR3 homologs were simultaneously mutated, mutants exhibited complete male sterility, and fertility could be easily restored by exogenous MeJA treatment. Hybrids produced from crosses between the opr3 sterile lines and normal varieties exhibited heterosis. This new two-line system based on OPR3 mutation provides higher stability and convenience than traditional systems. By using exogenous MeJA treatment to restore fertility, the system enables more precise control of male fertility transition, which has great potential to significantly contribute to the maneuverable production of hybrid seeds in rapeseed as well as other Brassica species crops.