Tuning Octahedron Sites of CoV2O4 via Cationic Competition for Efficient Oxygen Evolution Reaction.

Doping transition metal oxide spinels with metal ions represents a significant strategy for optimizing the electronic structure of electrocatalysts. Herein, a bimetallic Fe and Ru doping strategy to fine-tune the crystal structure of CoV2O4 spinel for highly enhanced oxygen evolution reaction (OER) is presented performance. The incorporation of Fe and Ru is observed at octahedral sites within the CoV2O4 structure, effectively modulating the electronic configuration of Co. Density functional theory calculations have confirmed that Fe acts as a novel reactive site, replacing V. Additionally, the synergistic effect of Fe, Co, and Ru effectively optimizes the Gibbs free energy of the intermediate species, reduces the reaction energy barrier, and accelerates the kinetics toward OER. As expected, the best-performing CoVFe0.5Ru0.5O4 displays a low overpotential of 240 mV (@10 mA cm-2) and a remarkably low Tafel slope of 38.9 mV dec-1, surpassing that of commercial RuO2. Moreover, it demonstrates outstanding long-term durability lasting for 72 h. This study provides valuable insights for the design of highly active polymetallic spinel electrocatalysts for energy conversion applications.

B vitamins and bone health: a meta-analysis with trial sequential analysis of randomized controlled trials.

Our study showed that B vitamins did not have significant effect on fracture incidence, bone mineral density, and bone turnover markers. However, the research data of B vitamins on bone mineral density and bone turnover markers are limited, and more clinical trials are needed to draw sufficient conclusions. PURPOSE: The objective of this study was to identify the efficacy of B vitamin (VB) (folate, B6, and B12) supplements on fracture incidence, bone mineral density (BMD), and bone turnover markers (BTMs). METHODS: A comprehensive search was performed in PubMed, MEDLINE, EMBASE, Cochrane databases, and ClinicalTrials.gov up to September 4, 2023. The risk of bias was assessed according to Cochrane Handbook and the quality of evidence was assessed according to the GRADE system. We used trial sequential analysis (TSA) to assess risk of random errors and Stata 14 to conduct sensitivity and publication bias analyses. RESULTS: Data from 14 RCTs with 34,700 patients were extracted and analyzed. The results showed that VBs did not significantly reduce the fracture incidence (RR, 1.06; 95% CI, 0.95 - 1.18; p = 0.33; I2 = 40%) and did not affect BMD in lumbar spine and femur neck. VBs had no significant effect on bone specific alkaline phase (a biomarker for bone formation), but could increase the serum carboxy-terminal peptide (a biomarker for bone resorption) (p = 0.009; I2 = 0%). The TSA showed the results of VBs on BMD and BTMs may not be enough to draw sufficient conclusions due to the small number of sample data included and needed to be demonstrated in more clinical trials. The inability of VBs to reduce fracture incidence has been verified by TSA as sufficient. Sensitivity analysis and publication bias assessment proved that our meta-analysis results were stable and reliable, with no significant publication bias. CONCLUSIONS: Available evidence from RCTs does not support VBs can effectively influence osteoporotic fracture risk, BMD, and BTMs. TRIAL REGISTRATION: PROSPERO registration number: CRD42023427508.

Multiple diffusion models for predicting pathologic response of esophageal squamous cell carcinoma to neoadjuvant chemotherapy.

BACKGROUND: To assess the feasibility and diagnostic performance of the fractional order calculus (FROC), continuous-time random-walk (CTRW), diffusion kurtosis imaging (DKI), intravoxel incoherent motion (IVIM), mono-exponential (MEM) and stretched exponential models (SEM) for predicting response to neoadjuvant chemotherapy (NACT) in patients with esophageal squamous cell carcinoma (ESCC). MATERIALS AND METHODS: This study prospectively included consecutive ESCC patients with baseline and follow up MR imaging and pathologically confirmed cT1-4aN + M0 or T3-4aN0M0 and underwent radical resection after neoadjuvant chemotherapy (NACT) between July 2019 and January 2023. Patients were divided into pCR (TRG 0) and non-pCR (TRG1 + 2 + 3) groups according to tumor regression grading (TRG). The Pre-, Post- and Delta-treatment models were built. 18 predictive models were generated according to different feature categories, based on six models by five-fold cross-validation. Areas under the curve (AUCs) of the models were compared by using DeLong method. RESULTS: Overall, 90 patients (71 men, 19 women; mean age, 64 years ± 6 [SD]) received NACT and underwent baseline and Post-NACT esophageal MRI, with 29 patients in the pCR group and 61 patients in the non-pCR group. Among 18 predictive models, The Pre-, Post-, and Delta-CTRW model showed good predictive efficacy (AUC = 0.722, 0.833 and 0.790). Additionally, the Post-FROC model (AUC = 0.907) also exhibited good diagnostic performance. CONCLUSIONS: Our study indicates that the CTRW model, along with the Post-FROC model, holds significant promise for the future of NACT efficacy prediction in ESCC patients.

Downstream-of-gene (DoG) transcripts contribute to an imbalance in the cancer cell transcriptome.

Downstream-of-gene (DoG) transcripts are an emerging class of noncoding RNAs. However, it remains largely unknown how DoG RNA production is regulated and whether alterations in DoG RNA signatures exist in major cancers. Here, through transcriptomic analyses of matched tumors and nonneoplastic tissues and cancer cell lines, we reveal a comprehensive catalog of DoG RNA signatures. Through separate lines of evidence, we support the biological importance of DoG RNAs in carcinogenesis. First, we show tissue-specific and stage-specific differential expression of DoG RNAs in tumors versus paired normal tissues with their respective host genes involved in tumor-promoting versus tumor-suppressor pathways. Second, we identify that differential DoG RNA expression is associated with poor patient survival. Third, we identify that DoG RNA induction is a consequence of treating colon cancer cells with the topoisomerase I (TOP1) poison camptothecin and following TOP1 depletion. Our results underlie the significance of DoG RNAs and TOP1-dependent regulation of DoG RNAs in diversifying and modulating the cancer transcriptome.

PEGylation renders carnosine resistant to hydrolysis by serum carnosinase and increases renal carnosine levels.

Carnosine's protective effect in rodent models of glycoxidative stress have provided a rational for translation of these findings in therapeutic concepts in patient with diabetic kidney disease. In contrast to rodents however, carnosine is rapidly degraded by the carnosinase-1 enzyme. To overcome this hurdle, we sought to protect hydrolysis of carnosine by conjugation to Methoxypolyethylene glycol amine (mPEG-NH2). PEGylated carnosine (PEG-car) was used to study the hydrolysis of carnosine by human serum as well as to compare the pharmacokinetics of PEG-car and L-carnosine in mice after intravenous (IV) injection. While L-carnosine was rapidly hydrolyzed in human serum, PEG-car was highly resistant to hydrolysis. Addition of unconjugated PEG to carnosine or PEG-car did not influence hydrolysis of carnosine in serum. In mice PEG-car and L-carnosine exhibited similar pharmacokinetics in serum but differed in half-life time (t1/2) in kidney, with PEG-car showing a significantly higher t1/2 compared to L-carnosine. Hence, PEGylation of carnosine is an effective approach to prevent carnosine degradations and to achieve higher renal carnosine levels. However, further studies are warranted to test if the protective properties of carnosine are preserved after PEGylation.

microRNA-8514-5p regulates adipokinetic hormone/corazonin-related peptide receptor to affect development and reproduction of Plutella xylostella.

BACKGROUND: Dicer1 plays a crucial role in regulating the development and reproduction of insects. Knockout of Dicer1 causes pupal deformity, low eclosion and low fecundity in Plutella xylostella, but the mechanism behind this phenomenon is not clear. This study aims to identify differentially-expressed genes and miRNAs in the Dicer1-knockout strain (ΔPxDcr-1) and assess their impact on the reproduction and development of P. xylostella. RESULTS: The knockout of Dicer1 affected the expression of genes including the adipokinetic hormone/corazonin-related peptide receptor (PxACPR). The expression of PxACPR was upregulated, and the expression of miR-8514-5p was downregulated in ΔPxDcr-1 of P. xylostella. The dual luciferase reporter assay and pull-down assay showed that miR-8514-5p bound to PxACPR in vitro and in vivo. The expression profiles demonstrated a negative correlation between PxACPR mRNA and miR-8514-5p in different developmental stages of the wild-type strain. Both the miR-8514-5p agomir and double-stranded RNA of ACPR (dsPxACPR) injected into the pre-pupae inhibited the mRNA level of PxACPR, causing high mortality and deformity of pupae, and low fecundity and hatching rate, which were consistent with the phenotype of ΔPxDcr-1. The injection of miR-8514-5p antagomir caused a similar phenotype to the injection of miR-8514-5p agomir. Additionally, the injection of miR-8514-5p antagomir significantly rescued the phenotype caused by dsPxACPR. CONCLUSION: These results indicate that miR-8514-5p affects the development and reproduction of P. xylostella by regulating PxACPR, and the homeostasis of PxACPR expression is essential for the development and reproduction of P. xylostella. © 2024 Society of Chemical Industry.

Enhanced Glycosylation Caused by Overexpression of Rv1002c in a Recombinant BCG Promotes Immune Response and Protects against Mycobacterium tuberculosis Infection.

Tuberculosis (TB) is a major global health threat despite its virtual elimination in developed countries. Issues such as drug accessibility, emergence of multidrug-resistant strains, and limitations of the current BCG vaccine highlight the urgent need for more effective TB control measures. This study constructed BCG strains overexpressing Rv1002c and found that the rBCG-Rv1002c strain secreted more glycosylated proteins, significantly enhancing macrophage activation and immune protection against Mycobacterium tuberculosis (M. tb). These results indicate that Rv1002c overexpression promotes elevated levels of O-glycosylation in BCG bacteriophages, enhancing their phagocytic and antigenic presentation functions. Moreover, rBCG-Rv1002c significantly upregulated immune regulatory molecules on the macrophage surface, activated the NF-κB pathway, and facilitated the release of large amounts of NO and H2O2, thereby enhancing bacterial control. In mice, rBCG-Rv1002c immunization induced greater innate and adaptive immune responses, including increased production of multifunctional and long-term memory T cells. Furthermore, rBCG-Rv1002c-immunized mice exhibited reduced lung bacterial load and histological damage upon M. tb infection. This result shows that it has the potential to be an excellent candidate for a preventive vaccine against TB.

Diterpenoids from the Aerial Parts of Isodon serra with Selective Cytotoxic Activity.

Four new diterpenoids, isodosins A-D (1-4), together with nine known compounds (5-13) were isolated and identified from the aerial parts of Isodon serra (Maxim.) Hara. The structures of the new diterpenoids were elucidated based on the analysis of HR-ESI-MS data, 1D/2D-NMR-spectroscopic data, and electronic circular dichroism (ECD) calculations. Cytotoxicities of compounds 2, 3, 5, 6, and 9 against the HepG2 and H1975 cell lines were evaluated with the MTT assay. As a result, compounds 2, 3, and 6 revealed higher levels of cytotoxicity against HepG2 cells than against H1975 cells. Moreover, compund 6 demonstrated the most efficacy in inhibiting the proliferation of HepG2 cells, with an IC50 value of 41.13 ± 3.49 µM. This effect was achieved by inducing apoptosis in a dose-dependent manner. Furthermore, the relationships between the structures and activities of these compounds are briefly discussed.

CMRxRecon: A publicly available k-space dataset and benchmark to advance deep learning for cardiac MRI.

Cardiac magnetic resonance imaging (CMR) has emerged as a valuable diagnostic tool for cardiac diseases. However, a significant drawback of CMR is its slow imaging speed, resulting in low patient throughput and compromised clinical diagnostic quality. The limited temporal resolution also causes patient discomfort and introduces artifacts in the images, further diminishing their overall quality and diagnostic value. There has been growing interest in deep learning-based CMR imaging algorithms that can reconstruct high-quality images from highly under-sampled k-space data. However, the development of deep learning methods requires large training datasets, which have so far not been made publicly available for CMR. To address this gap, we released a dataset that includes multi-contrast, multi-view, multi-slice and multi-coil CMR imaging data from 300 subjects. Imaging studies include cardiac cine and mapping sequences. The 'CMRxRecon' dataset contains raw k-space data and auto-calibration lines. Our aim is to facilitate the advancement of state-of-the-art CMR image reconstruction by introducing standardized evaluation criteria and making the dataset freely accessible to the research community.

Causal effect of physical activity and sedentary behavior on the risk of alcohol dependence: A bidirectional two-sample Mendelian randomization study.

BACKGROUND: Alcohol dependence, influenced by physical activity (PA) and sedentary behavior, lacks clear causal clarity. This study aims to clarify causal relationships by estimating these effects using bidirectional two-sample Mendelian randomization (MR). METHODS: A bidirectional multivariable two-sample MR framework was employed to assess the causal effects of PA and sedentary behavior on alcohol dependence. Summarized genetic association data were analyzed for four PA-related activity patterns-moderate to vigorous physical activity (MVPA), vigorous physical activity (VPA), accelerometer-based physical activity with average acceleration (AccAve), and accelerometer-based physical activity with accelerations greater than 425 milli-gravities (Acc425)-and three sedentary behavior patterns-sedentary, TV watching, and computer use. The study was expanded to include the examination of the relationship between sedentary behavior or PA and general drinking behavior, quantified as drinks per week (DPW). We obtained summarized data on genetic associations with four PA related activity patterns (MVPA, VPA, AccAve and Acc425) and three sedentary behavior related behavior patterns (sedentary, TV watching and computer use). RESULTS: MR analysis found AccAve inversely associated with alcohol dependence risk (OR: 0.87; 95% CI: 0.80-0.95; p < 0.001), MVPA positively associated (OR: 2.86; 95%CI: 1.45-5.66; p = 0.002). For sedentary behavior and alcohol dependence, only TV watching was positively associated with the risk of alcohol dependence (OR: 1.43; 95%CI: 1.09-1.88; p = 0.009). No causal links found for other physical or sedentary activities. Reverse analysis and sensitivity tests showed consistent findings without pleiotropy or heterogeneity. Multivariate MR analyses indicated that while MVPA, AccAve and TV watching are independently associated with alcohol dependence, DPW did not show a significant causal relationship. CONCLUSIONS: Our results suggest that AccAve is considered a protective factor against alcohol dependence, while MVPA and TV watching are considered risk factors for alcohol dependence. Conversely, alcohol dependence serves as a protective factor against TV watching. Only TV watching and alcohol dependence might mutually have a significant causal effect on each other.

Research on building extraction from remote sensing imagery using efficient lightweight residual network.

Automatic building extraction from very high-resolution remote sensing images is of great significance in several application domains, such as emergency information analysis and intelligent city construction. In recent years, with the development of deep learning technology, convolutional neural networks (CNNs) have made considerable progress in improving the accuracy of building extraction from remote sensing imagery. However, most existing methods require numerous parameters and large amounts of computing and storage resources. This affects their efficiency and limits their practical application. In this study, to balance the accuracy and amount of computation required for building extraction, a novel efficient lightweight residual network (ELRNet) with an encoder-decoder structure is proposed for building extraction. ELRNet consists of a series of downsampling blocks and lightweight feature extraction modules (LFEMs) for the encoder and an appropriate combination of LFEMs and upsampling blocks for the decoder. The key to the proposed ELRNet is the LFEM which has depthwise-factorised convolution incorporated in its design. In addition, the effective channel attention (ECA) added to LFEM, performs local cross-channel interactions, thereby fully extracting the relevant information between channels. The performance of ELRNet was evaluated on the public WHU Building dataset, achieving 88.24% IoU with 2.92 GFLOPs and 0.23 million parameters. The proposed ELRNet was compared with six state-of-the-art baseline networks (SegNet, U-Net, ENet, EDANet, ESFNet, and ERFNet). The results show that ELRNet offers a better tradeoff between accuracy and efficiency in the automatic extraction of buildings in very highresolution remote sensing images. This code is publicly available on GitHub (https://github.com/GaoAi/ELRNet).

Casual associations between brain structure and sarcopenia: A large-scale genetic correlation and mendelian randomization study.

Sarcopenia presenting a critical challenge in population-aging healthcare. The elucidation of the interplay between brain structure and sarcopenia necessitates further research. The aim of this study is to explore the casual association between brain structure and sarcopenia. Linkage disequilibrium score regression (LDSC) was conducted to estimate the genetic correlations; MR was then performed to explore the causal relationship between Brain imaging-derived phenotypes (BIDPs) and three sarcopenia-related traits: handgrip strength, walking pace, and appendicular lean mass (ALM). The main analyses were conducted using the inverse-variance weighted method. Moreover, weighted median and MR-Egger were conducted as sensitivity analyses. Genetic association between 6.41% of BIDPs and ALM was observed, and 4.68% of BIDPs exhibited causal MR association with handgrip strength, 2.11% of BIDPs were causally associated with walking pace, and 2.04% of BIDPs showed causal association with ALM. Volume of ventromedial hypothalamus was associated with increased odds of handgrip strength (OR: 1.18, 95% CI: 1.02 to 1.37) and ALM (OR: 1.05, 95% CI: 1.01 to 1.09). Mean thickness of G-pariet-inf-Angular was associated with decreased odds of handgrip strength (OR: 0.83, 95% CI: 0.70 to 0.97) and walking pace (OR: 0.97, 95% CI: 0.93 to 0.99). As part of the brain structure forward causally influences sarcopenia, which may provide new perspectives for the prevention of sarcopenia and offer valuable insights for further research on the brain-muscle axis.

Machine Learning-Guided Prediction of Desalination Capacity and Rate of Porous Carbons for Capacitive Deionization.

Nowadays, capacitive deionization (CDI) has emerged as a prominent technology in the desalination field, typically utilizing porous carbons as electrodes. However, the precise significance of electrode properties and operational conditions in shaping desalination performance remains blurry, necessitating numerous time-consuming and resource-intensive CDI experiments. Machine learning (ML) presents an emerging solution, offering the prospect of predicting CDI performance with minimal investment in electrode material synthesis and testing. Herein, four ML models are used for predicting the CDI performance of porous carbons. Among them, the gradient boosting model delivers the best performance on test set with low root mean square error values of 2.13 mg g-1 and 0.073 mg g-1 min-1 for predicting desalination capacity and rate, respectively. Furthermore, SHapley Additive exPlanations is introduced to analyze the significance of electrode properties and operational conditions. It highlights that electrolyte concentration and specific surface area exert a substantially more influential role in determining desalination performance compared to other features. Ultimately, experimental validation employing metal-organic frameworks-derived porous carbons and biomass-derived porous carbons as CDI electrodes is conducted to affirm the prediction accuracy of ML models. This study pioneers ML techniques for predicting CDI performance, offering a compelling strategy for advancing CDI technology.

Injectable cartilage microtissues based on 3D culture using porous gelatin microcarriers for cartilage defect treatment.

Cartilage tissues possess an extremely limited capacity for self-repair, and current clinical surgical approaches for treating articular cartilage defects can only provide short-term relief. Despite significant advances in the field of cartilage tissue engineering, avoiding secondary damage caused by invasive surgical procedures remains a challenge. In this study, injectable cartilage microtissues were developed through 3D culture of rat bone marrow mesenchymal stem cells (BMSCs) within porous gelatin microcarriers (GMs) and induced differentiation. These microtissues were then injected for the purpose of treating cartilage defects in vivo, via a minimally invasive approach. GMs were found to be noncytotoxic and favorable for cell attachment, proliferation and migration evaluated with BMSCs. Moreover, cartilage microtissues with a considerable number of cells and abundant extracellular matrix components were obtained from BMSC-laden GMs after induction differentiation culture for 28 days. Notably, ATDC5 cells were complementally tested to verify that the GMs were conducive to cell attachment, proliferation, migration and chondrogenic differentiation. The microtissues obtained from BMSC-laden GMs were then injected into articular cartilage defect areas in rats and achieved superior performance in alleviating inflammation and repairing cartilage. These findings suggest that the use of injectable cartilage microtissues in this study may hold promise for enhancing the long-term outcomes of cartilage defect treatments while minimizing the risk of secondary damage associated with traditional surgical techniques.

Antibiotic fermentation residue for biohydrogen production: Inhibitory mechanisms of the inherent antibiotic.

Antibiotic fermentation residue, which is generated from the microbial antibiotic production process, has been a troublesome waste faced by the pharmaceutical industry. Dark fermentation is a potential technology to treat antibiotic fermentation residue in terms of renewable H2 generation and waste management. However, the inherent antibiotic in antibiotic fermentation residue may inhibit its dark fermentation performance, and current understanding on this topic is limited. This investigation examined the impact of the inherent antibiotic on the dark H2 fermentation of Cephalosporin C (CEPC) fermentation residue, and explored the mechanisms from the perspectives of bacterial communities and functional genes. It was found that CEP-C in the antibiotic fermentation residue significantly inhibited the H2 production, with the H2 yield decreasing from 17.2 mL/g-VSadded to 12.5 and 9.6 mL/g-VSadded at CEP-C concentrations of 100 and 200 mg/L, respectively. CEP-C also prolonged the H2-producing lag period. Microbiological analysis indicated that CEP-C remarkably decreased the abundances of high-yielding H2-producing bacteria, as well as downregulated the genes involved in hydrogen generation from the"pyruvate pathway" and"NADH pathway", essentially leading to the decline of H2 productivity. The present work gains insights into how cephalosporin antibiotics influence the dark H2 fermentation, and provide guidance for mitigating the inhibitory effects.

Structure-guided conversion from an anaplastic lymphoma kinase inhibitor into Plasmodium lysyl-tRNA synthetase selective inhibitors.

Aminoacyl-tRNA synthetases (aaRSs) play a central role in the translation of genetic code, serving as attractive drug targets. Within this family, the lysyl-tRNA synthetase (LysRS) constitutes a promising antimalarial target. ASP3026, an anaplastic lymphoma kinase (ALK) inhibitor was recently identified as a novel Plasmodium falciparum LysRS (PfLysRS) inhibitor. Here, based on cocrystal structures and biochemical experiments, we developed a series of ASP3026 analogues to improve the selectivity and potency of LysRS inhibition. The leading compound 36 showed a dissociation constant of 15.9 nM with PfLysRS. The inhibitory efficacy on PfLysRS and parasites has been enhanced. Covalent attachment of L-lysine to compound 36 resulted in compound 36K3, which exhibited further increased inhibitory activity against PfLysRS but significantly decreased activity against ALK. However, its inhibitory activity against parasites did not improve, suggesting potential future optimization directions. This study presents a new example of derivatization of kinase inhibitors repurposed to inhibit aaRS.

Multifunctional nano-in-micro delivery systems for targeted therapy in fundus neovascularization diseases.

Fundus neovascularization diseases are a series of blinding eye diseases that seriously impair vision worldwide. Currently, the means of treating these diseases in clinical practice are continuously evolving and have rapidly revolutionized treatment opinions. However, key issues such as inadequate treatment effectiveness, high rates of recurrence, and poor patient compliance still need to be urgently addressed. Multifunctional nanomedicine can specifically respond to both endogenous and exogenous microenvironments, effectively deliver drugs to specific targets and participate in activities such as biological imaging and the detection of small molecules. Nano-in-micro (NIM) delivery systems such as metal, metal oxide and up-conversion nanoparticles (NPs), quantum dots, and carbon materials, have shown certain advantages in overcoming the presence of physiological barriers within the eyeball and are widely used in the treatment of ophthalmic diseases. Few studies, however, have evaluated the efficacy of NIM delivery systems in treating fundus neovascular diseases (FNDs). The present study describes the main clinical treatment strategies and the adverse events associated with the treatment of FNDs with NIM delivery systems and summarizes the anatomical obstacles that must be overcome. In this review, we wish to highlight the principle of intraocular microenvironment normalization, aiming to provide a more rational approach for designing new NIM delivery systems to treat specific FNDs.

Phenotype, Biomass, Carbon and Nitrogen Assimilation, and Antioxidant Response of Rapeseed under Salt Stress.

Salt stress is one of the major adverse factors affecting plant growth and crop production. Rapeseed is an important oil crop, providing high-quality edible oil for human consumption. This experiment was conducted to investigate the effects of salt stress on the phenotypic traits and physiological processes of rapeseed. The soil salinity was manipulated by setting three different levels: 0 g NaCl kg-1 soil (referred to as S0), 1.5 g NaCl kg-1 soil (referred to as S1), and 3.0 g NaCl kg-1 soil (referred to as S2). In general, the results indicated that the plant height, leaf area, and root neck diameter decreased with an increase in soil salinity. In addition, the biomass of various organs at all growth stages decreased as soil salinity increased from S0 to S2. The increasing soil salinity improved the distribution of biomass in the root and leaf at the seedling and flowering stages, indicating that rapeseed plants subjected to salt stress during the vegetative stage are capable of adapting their growth pattern to sustain their capacity for nutrient and water uptake, as well as leaf photosynthesis. However, as the soil salinity increased, there was a decrease in the distribution of biomass in the pod and seed at the maturity stage, while an increase was observed in the root and stem, suggesting that salt stress inhibited carbohydrate transport into reproductive organs. Moreover, the C and N accumulation at the flowering and maturity stages exhibited a reduction in direct correlation with the increase in soil salinity. High soil salinity resulted in a reduction in the C/N, indicating that salt stress exerted a greater adverse effect on C assimilation compared to N assimilation, leading to an increase in seed protein content and a decrease in oil content. Furthermore, as soil salinity increased from S0 to S2, the activity of superoxide dismutase (SOD) and catalase (CAT) and the content of soluble protein and sugar increased by 58.39%, 33.38%, 15.57%, and 13.88% at the seedling stage, and 38.69%, 22.85%, 12.04%, and 8.26% at the flowering stage, respectively. In summary, this study revealed that salt stress inhibited C and N assimilation, leading to a suppressed phenotype and biomass accumulation. The imbalanced C and N assimilation under salt stress contributed to the alterations in the seed oil and protein content. Rapeseed had a certain degree of salt tolerance by improving antioxidants and osmolytes.

PICALM::MLLT10 may indicate a new subgroup of acute leukemias with miscellaneous immunophenotype and poor initial treatment response but showing sensitivity to venetoclax.

The PICALM::MLLT10 fusion gene is a rare but recurrent event in acute leukemia (AL) associated with poor prognosis. It is still confused whether PICALM::MLLT10 can solely correspond to acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) or acute leukemias of ambiguous lineage (ALAL). Here, we reported a series of PICALM::MLLT10 positive AL patients with miscellaneous immunophenotype including T-ALL, ALAL, AML, and B-ALL, complex karyotype, half of extramedullary disease (EMD), frequently concomitant PHF6 mutation, and poor initial treatment response to standard chemotherapy aiming to different immunophenotype, but showing sensitivity to combining chemotherapy especially integrated with venetoclax, suggesting this fusion gene may indicate a new subgroup of AL. Eighteen PICALM::MLLT10 positive patients of 533 AL patients (18/533, 3.4%) were identified by RNA sequencing in our center. We found PICALM::MLLT10 positive AL showing miscellaneous immunophenotype, higher expression of leukemic stemness genes and lower expression of biomarkers of venetoclax resistance, more extramedullary involvement, and especially poor response to conventional induction chemotherapy, but may benefit from venetoclax as well as low-dose Ara-C, granulocyte colony-stimulating factor (G-CSF), and anthracyclines combination chemotherapy. Sequential hematopoietic stem cell transplantation (HSCT) after chemotherapy combined with venetoclax may further improve long-term survival in AL patients with complete remission (CR) even measurable residual disease (MRD) positive.