Nonlinear Relationship Between Homocysteine and Mild Cognitive Impairment in Early Parkinson's Disease: A Cross-Sectional Study.

Background: Cognitive impairment, a prevalent non-motor symptom in advanced Parkinson's disease (PD), has been associated with hyperhomocysteinemia, an important risk factor for PD progression and cognitive decline in PD. However, evidence regarding the association between homocysteine (Hcy) and cognitive function during early PD remains insufficient. Therefore, this study aims to examine the correlation between Hcy levels and cognitive function in the early stage of PD. Methods: The study included 218 individuals in the early stages of PD who were consecutively admitted to the Suining Central Hospital Neurology Department. All the individuals completed the Parkinson's Disease Cognitive Rating Scale (PD-CDR). The Unified Parkinson's Disease Rating Scale part III (UPDRS-III) was employed for measuring the severity of motor symptoms, while the Hoehn-Yahr scale was used to measure the clinical symptom stage. Fasting venous blood samples were also drawn to measure the Hcy concentration, red blood cell folate, and vitamin B12. Results: In this cross-sectional study, 47 (21.5%) patients with PD showed cognitive dysfunction. The serum Hcy levels were significantly higher in the cognitive impairment PD (PDCI) group compared with the cognitive normal PD group (P<0.001). The Generalized Additive Model (GAM) analysis revealed a nonlinear relationship between Hcy and the risk of PDCI. Multiple logistic regression analyses demonstrated a positive relationship between elevated Hcy and the risk of PDCI in the fully adjusted model ([OR]:3.1, 95% CI, 1.1-8.5, P=0.028). Segmented linear regression analysis showed that when Hcy levels were above 17.7 umol/l, the risk of PDCI increased by 1.6 times for every 1 unit elevated in Hcy (95% CI:1.1-2.2, P=0.008). Conclusion: This study revealed a nonlinear positive correlation between the risk of PDCI and elevated serum Hcy levels in early PD patients, suggesting hyperhomocysteinemia as one of the treatable factors for cognitive impairment in the early stages of PD.

Sequential activation of strigolactone and salicylate biosynthesis promotes leaf senescence.

Leaf senescence is a complex process strictly regulated by various external and endogenous factors. However, the key signaling pathway mediating leaf senescence remains unknown. Here, we show that Arabidopsis SPX1/2 negatively regulate leaf senescence genetically downstream of the strigolactone (SL) pathway. We demonstrate that the SL receptor AtD14 and MAX2 mediate the age-dependent degradation of SPX1/2. Intriguingly, we uncover an age-dependent accumulation of SLs in leaves via transcriptional activation of SL biosynthetic genes by the transcription factors (TFs) SPL9/15. Furthermore, we reveal that SPX1/2 interact with the WRKY75 subclade TFs to inhibit their DNA-binding ability and thus repress transcriptional activation of salicylic acid (SA) biosynthetic gene SA Induction-Deficient 2, gating the age-dependent SA accumulation in leaves at the leaf senescence onset stage. Collectively, our new findings reveal a signaling pathway mediating sequential activation of SL and salicylate biosynthesis for the onset of leaf senescence in Arabidopsis.

Q negatively regulates wheat salt tolerance through directly repressing the expression of TaSOS1 and reactive oxygen species scavenging genes.

The Q transcription factor plays important roles in improving multiple wheat domestication traits such as spike architecture, threshability and rachis fragility. However, whether and how it regulates abiotic stress adaptation remain unclear. We found that the transcriptional expression of Q can be induced by NaCl and abscisic acid treatments. Using the q mutants generated by CRISPR/Cas9 and Q overexpression transgenic lines, we showed that the domesticated Q gene causes a penalty in wheat salt tolerance. Then, we demonstrated that Q directly represses the transcription of TaSOS1-3B and reactive oxygen species (ROS) scavenging genes to regulate Na+ and ROS homeostasis in wheat. Furthermore, we showed that wheat salt tolerance protein TaWD40 interacts with Q to competitively interfere with the interaction between Q and the transcriptional co-repressor TaTPL. Taken together, our findings reveal that Q directly represses the expression of TaSOS1 and some ROS scavenging genes, thus causing a harmful effect on wheat salt tolerance.

The sonographic features of lymph node venous networks and flow patterns in patients with primary chronic venous disease.

BACKGROUND: Our study aims to enhance the understanding of lymph node venous networks (LNVNs) by summarising their anatomical, sonographic features, and reflux patterns. METHOD: We examined 241 legs from 141 patients with primary chronic venous disease (CVD) using duplex ultrasound. RESULTS: The findings indicated variations in the shape, size, vascularity, and echogenicity of LNVN. The superficial inguinal lymph node with reflux appeared slightly larger, exhibiting higher velocities in the hilar artery. Regarding connections, venous flow within LNVN was predominantly drained through the saphenofemoral junction (SFJ), anterior accessory great saphenous vein (AAGSV), and great saphenous vein (GSV). A significant number of LNVNs were observed to be associated with anterolateral thigh tributaries. The study also identified valve cusps within LNVN. CONCLUSION: This study revealed a 12% prevalence of primary LNVN. Understanding the anatomical and haemodynamic features of LNVN informs treatment strategies and potentially helps prevent the recurrence of varicose veins.

A large cross sectional study on diaper utilization and beneficial role in outdoor activity and emotions among incontinence elderly people.

This study was designed based on a cross-sectional investigation conducted Shanghai, China. Demographic characteristics, diaper utilization, Activities of Daily Living (ADL) and emotion were collected by Unified Needs Assessment Form for Elderly Care Questionnaire. Cognition function was assessed by Mini-mental State Examination (MMSE) scale. Multivariate logistic regression was used for statistical analysis. The diaper utilization rate was 31.2%. Female, higher level of education, poorer ADL and cognition, more severe incontinence and financial dependence on others were facilitating factors for diaper usage (P < 0.05). The possibility of using diaper differed according to the intimacy of caregivers. Among incontinent individuals with relatively good ADL and cognition level, diaper utilization can significantly decrease the risk of going out only once a month (OR: 2.63 vs 4.05), and going out less than once a month (OR: 5.32 vs 6.53). Incontinence people who going out at least once a week had a lower risk of some negative emotion. Significantly, diaper utilization further decreased this risk. In conclusion, for incontinence elderly people with relatively independent ability, proper use of diaper may improve the frequency of outdoor activity and emotion. Nevertheless, diaper utilization should be decided based on elderly people's own will.

PvARL1 Increases Biomass Yield and Enhances Alkaline Tolerance in Switchgrass (Panicum virgatum L.).

Switchgrass is an important bioenergy crop valued for its biomass yield and abiotic tolerance. Alkali stress is a major abiotic stress that significantly impedes plant growth and yield due to high salinity and pH; however, the response mechanism of switchgrass to alkali stress remains limited. Here, we characterized PvARL1, an ARF-like gene, which was up-regulated in both the shoot and root tissues under alkali stress conditions. Overexpression of PvARL1 not only improved alkali tolerance but also promoted biomass yield with more tiller and higher plant height in switchgrass. Moreover, PvARL1 overexpression lines displayed higher capacities in the maintenance of water content and photosynthetic stability compared with the controls under alkali treatments. A significant reduction in the ratio of electrolyte leakage, MDA content, and reactive oxygen species (ROS) showed that PvARL1 plays a positive role in protecting cell membrane integrity. In addition, PvARL1 also negatively affected the K+ efflux or uptake in roots to alleviate ion toxicity under alkali treatments. Overall, our results suggest that PvARL1 functions as a positive regulator in plant growth as well as in the plant response to alkali stress, which could be used to improve switchgrass biomass yield and alkali tolerance genetically.

Relationship between glycated hemoglobin levels at admission and chronic post-stroke fatigue in patients with acute ischemic stroke.

BACKGROUND: Chronic Post-Stroke Fatigue (PSF) is a common and persistent complications among ischemic stroke survivors. The serum glycated hemoglobin (HbA1c) level, as it is known has emerged as a critical risk factor for Acute Ischemic Stroke (AIS) and post-stroke cognitive and emotional impairment. However, no studies have been conducted on the link between HbA1c and PSF. Therefore, this study aims to estimate the relationship between HbA1c and PSF in the chronic phase. METHODS: A longitudinal study was conducted on 559 patients diagnosed with their first AIS episode and admitted to Suining Central Hospital within three days after onset. All patients were examined for serum HbA1c, blood glucose levels and routine blood biochemical indicators at admission. The Fatigue Severity Scale (FSS) was employed to assess fatigue symptoms at six months post-stroke. Multivariate logistic regression and smooth curve fitting were used to analyze the relationship between admission HbA1c, blood glucose levels, discharge blood glucose and PSF, and the predictive value of HbA1c on PSF was assessed using a segmented linear regression model. RESULTS: 189(33.8 %)of the 559 patients included in the study, reported PSF at six-month follow-up. Compared with the non-PSF group, the PSF group displayed significantly higher levels of HbA1c (7.8 ± 3.0 vs 6.5 ± 2.0 %, P < 0.001), admission blood glucose (7.8 ± 3.8 vs 7.1 ± 3.5 mmol/L, P = 0.041), and discharge blood glucose (6.3 ± 1.6 vs 5.8 ± 1.2 mmol/L, P < 0.001). The dose-response relationship among admission HbA1c, blood glucose, discharge blood glucose and PSF showed that HbA1c level is positively and non-linearly related to the risk of PSF. A linear positive correlation is noted between PSF and discharge blood glucose levels, while no significant correlation was observed for the blood glucose levels upon admission. CONCLUSIONS: Higher HbA1c levels at admission were independently associated with the risk of chronic PSF, the correlation between blood glucose and PSF showed significant variability, HbA1c may serve as a more stable risk factor in predicting the occurrence of chronic PSF and long-term active glycemic management may have a favorable impact on chronic PSF after AIS.

The STF/WOX1 MD is required for physical interaction with MtWOX9 and leaf blade outgrowth in Medicago truncatula.

Plant-specific WUSCHEL-related homeobox (WOX) family transcription factors play critical roles in maintaining meristems and lateral organ development. The WUS clade member STF/LAM1 physically interacts with the intermediate clade member WOX9. This interaction contributes to their antagonistical functions on leaf blade outgrowth by competing for the same cis-elements in the promoter of their common target in M. truncatula and N. sylvestris. Here, we identified the main interaction domains of STF and MtWOX9 in Medicago, shedding light on the mechanism of WOX gene function. The middle domain of STF and MtWOX9 are both critical for the interaction, while the conserved motif of STF in the C-terminal domain is also required. Deletion of the middle domain of STF partially rescued the leaf blade phenotypes of the stf null mutant, indicating that the middle domain plays an essential role during leaf blade expansion. This finding provides a new insight that the versatility of WOX function is not only caused by the conserved DNA binding and repression domains but also by the middle domain that recruits different partners.

Hypoxia-induced miR-181a-5p up-regulation reduces epirubicin sensitivity in breast cancer cells through inhibiting EPDR1/TRPC1 to activate PI3K/AKT signaling pathway.

Breast carcinoma (BC) ranks as a predominant malignancy and constitutes the second principal cause of mortality among women globally. Epirubicin stands as the drug of choice for BC therapeutics. Nevertheless, the emergence of chemoresistance has significantly curtailed its therapeutic efficacy. The resistance mechanisms to Epirubicin remain not entirely elucidated, yet they are conjectured to stem from diminished tumor vascular perfusion and resultant hypoxia consequent to Epirubicin administration. In our investigation, we meticulously scrutinized the Gene Expression Omnibus database for EPDR1, a gene implicated in hypoxia and Epirubicin resistance in BC. Subsequently, we delineated the impact of EPDR1 on cellular proliferation, motility, invasive capabilities, and interstitial-related proteins in BC cells, employing methodologies such as the CCK-8 assay, Transwell assay, and western blot analysis. Our research further unveiled that hypoxia-induced miR-181a-5p orchestrates the regulation of BC cell duplication, migration, invasion, and interstitial-related protein expression via modulation of EPDR1. In addition, we identified TRPC1, a gene associated with EPDR1 expression in BC, and substantiated that EPDR1 influences BC cellular dynamics through TRPC1-mediated modulation of the PI3K/AKT signaling cascade. Our findings underscore the pivotal role of EPDR1 in the development of BC. EPDR1 was found to be expressed at subdued levels in BC tissues, Epirubicin-resistant BC cells, and hypoxic BC cells. The overexpression of EPDR1 curtailed BC cell proliferation, motility, invasiveness, and the expression of interstitial-related proteins. At a mechanistic level, the overexpression of hypoxia-induced miR-181a-5p was observed to inhibit the EPDR1/TRPC1 axis, thereby activating the PI3K/AKT signaling pathway and diminishing the sensitivity to Epirubicin in BC cells. In summation, our study demonstrates that the augmentation of hypoxia-induced miR-181a-5p diminishes Epirubicin sensitivity in BC cells by attenuating EPDR1/TRPC1 expression, thereby invigorating the PI3K/AKT signaling pathway. This exposition offers a theoretical foundation for the application of Epirubicin in BC therapy, marking a significant contribution to the existing body of oncological literature.

N6-methyladenosine analysis unveils key mechanisms underlying long-term salt stress tolerance in switchgrass (Panicum virgatum).

N6-methyladenosine (m6A) RNA modification is critical for plant growth, development, and environmental stress response. While short-term stress impacts on m6A are well-documented, the consequences of prolonged stress remain underexplored. This study conducts a thorough transcriptome-wide analysis of m6A modifications following 28-day exposure to 200 mM NaCl. We detected 11,149 differentially expressed genes (DEGs) and 12,936 differentially methylated m6A peaks, along with a global decrease in m6A levels. Notably, about 62% of m6A-modified DEGs, including demethylase genes like PvALKBH6_N, PvALKBH9_K, and PvALKBH10_N, showed increased expression and reduced m6A peaks, suggesting that decreased m6A methylation may enhance gene expression under salt stress. Consistent expression and methylation patterns were observed in key genes related to ion homeostasis (e.g., H+-ATPase 1, High-affinity K+transporter 5), antioxidant defense (Catalase 1/2, Copper/zinc superoxide dismutase 2, Glutathione synthetase 1), and osmotic regulation (delta 1-pyrroline-5-carboxylate synthase 2, Pyrroline-5-carboxylate reductase). These findings provide insights into the adaptive mechanisms of switchgrass under long-term salt stress and highlight the potential of regulating m6A modifications as a novel approach for crop breeding strategies focused on stress resistance.

Development of novel superconductivity with higher Tc via the suppression of magnetism in quasi-two-dimensional electride Y2C under high pressures.

Discovery of superconductivity in electride materials has been a topic of interest as their intrinsic electron-rich properties might suggest a considerable electron-phonon interaction.Layered Y2C is a ferromagnetic quasi-two-dimensional electride with polarized anionic electrons confined in the interlayer space. In this theoretical study, we report Y2C undergoes a series of structural phase transitions into two superconducting phases with estimated Tc of 9.2 and 21.0 K at 19 and 80 GPa, respectively, via the suppression of magnetism. Our extensive first-principles swarm structure searches identify that these two high-pressure superconducting phases possess an orthorhombic Pnma and a tetragonal I4/m structures, respectively, where the Pnma phase is found to be a one-dimensional electride characterized by electron confinements in channel spaces of the crystal lattice, while the electride property in I 4/m phase has been completely destroyed. We attribute the development of an unprecedentedly high Tc superconductivity in Y-C system to the destructions of magnetism and the delocalization of interlayered anionic electrons under pressures. This work provides a unique example of pressure-induced collapse of magnetism at the onset of superconductivity in electride materials, along with the dramatic changes of electron-confinement topology in crystal lattices.

A chromosome-level genome assembly for Onobrychis viciifolia reveals gene copy number gain underlying enhanced proanthocyanidin biosynthesis.

Sainfoin (Onobrychis viciifolia), which belongs to subfamily Papilionoideae of Leguminosae, is a vital perennial forage known as "holy hay" due to its high contents of crude proteins and proanthocyanidins (PAs, also called condensed tannins) that have various pharmacological properties in animal feed, such as alleviating rumen tympanic disease in ruminants. In this study, we select an autotetraploid common sainfoin (2n = 4x = 28) and report its high-quality chromosome-level genome assembly with 28 pseudochromosomes and four haplotypes (~1950.14 Mb, contig N50 = 10.91 Mb). The copy numbers of genes involved in PA biosynthesis in sainfoin are significantly greater than those in four selected Fabales species, namely, autotetraploid Medicago sativa and three other diploid species, Lotus japonicus, Medicago truncatula, and Glycine max. Furthermore, gene expansion is confirmed to be the key contributor to the increased expression of these genes and subsequent PA enhancement in sainfoin. Transcriptomic analyses reveal that the expression of genes involved in the PA biosynthesis pathway is significantly increased in the lines with high PA content compared to the lines with medium and low PA content. The sainfoin genome assembly will improve our understanding of leguminous genome evolution and biosynthesis of secondary metabolites in sainfoin.

A novel configuration for the fixation of intra-articular C2.3 distal humerus fractures with the potential for minimally invasive surgery: a biomechanical evaluation and finite element analysis.

BACKGROUND: Distal humerus fractures are a challenge to treat, and the current standard of care, open reduction internal fixation with a double-plate, has a high rate of complications. We proposed a novel internal fixation configuration, lateral intramedullary nail and medial plate (LINMP) and verified its rigidity through biomechanical tests and finite element analysis. METHODS: The study involved biomechanical testing of 30 synthetic humerus models to compare 2 different fixation systems for an AO 13C-2.3 type fracture. The orthogonal double-plate (ODP) group and the LINMP group were compared through biomechanical testing to measure stiffness and failure load fewer than 3 working conditions. Based on the results, we optimized the intramedullary nail by eliminating the holes at the distal end of the nail and incorporating a 2-hole external locking plate. The Finite element analysis was also conducted to further compare the modified LINMP configuration with the previous 2 fixation configurations. RESULTS: In biomechanical tests, the ODP group exhibited lower stiffness under bending and compression forces compared to the LINMP group, but higher stiffness and failure loads under torsion force. In finite element analysis, the modified LINMP reduces the maximum stress of the fixation structure without significantly reducing the stiffness under bending stress and axial compression conditions. In torsion stress conditions, the modified LINMP enhances both the maximum stress and the stiffness, although it remains marginally inferior to the ODP structure. CONCLUSION: Our study demonstrates that the innovative LINMP presents comparable or slightly superior concerning bending and axial loading compared to orthogonal double-plate osteosynthesis for distal humeral intra-articular fractures, which might become a minimally invasive option for these fractures.

ELF4 contributes to esophageal squamous cell carcinoma growth and metastasis by augmenting cancer stemness via FUT9.

Esophageal squamous cell carcinoma (ESCC) commonly has aggressive properties and a poor prognosis. Investigating the molecular mechanisms underlying the progression of ESCC is crucial for developing effective therapeutic strategies. Here, by performing transcriptome sequencing in ESCC and adjacent normal tissues, we find that E74-like transcription factor 4 (ELF4) is the main upregulated transcription factor in ESCC. The results of the immunohistochemistry show that ELF4 is overexpressed in ESCC tissues and is significantly correlated with cancer staging and prognosis. Furthermore, we demonstrate that ELF4 could promote cancer cell proliferation, migration, invasion, and stemness by in vivo assays. Through RNA-seq and ChIP assays, we find that the stemness-related gene fucosyltransferase 9 ( FUT9) is transcriptionally activated by ELF4. Meanwhile, ELF4 is verified to affect ESCC cancer stemness by regulating FUT9 expression. Overall, we first discover that the transcription factor ELF4 is overexpressed in ESCC and can promote ESCC progression by transcriptionally upregulating the stemness-related gene FUT9.

Shikonin exerts an anti-leukemia effect against FLT3-ITD mutated acute myeloid leukemia cells via targeting FLT3 tyrosine kinase and its downstream pathways.

INTRODUCTION: Acute myeloid leukemia (AML) with internal tandem duplication (ITD) mutations in Fms-like tyrosine kinase 3 (FLT3) has an unfavorable prognosis. Recently, using newly emerging inhibitors of FLT3 has led to improved outcomes of patients with FLT3-ITD mutations. However, drug resistance and relapse continue to be significant challenges in the treatment of patients with FLT3-ITD mutations. This study aimed to evaluate the anti-leukemic effects of shikonin (SHK) and its mechanisms of action against AML cells with FLT3-ITD mutations in vitro and in vivo. METHODS: The CCK-8 assay was used to analyze cell viability, and flow cytometry was used to detect cell apoptosis and differentiation. Western blotting and real-time polymerase chain reaction (RT-PCR) were used to examine the expression of certain proteins and genes. Leukemia mouse model was created to evaluate the anti-leukemia effect of SHK against FLT3-ITD mutated leukemia in vivo. RESULTS: After screening a series of leukemia cell lines, those with FLT3-ITD mutations were found to be more sensitive to SHK in terms of proliferation inhibition and apoptosis induction than those without FLT3-ITD mutations. SHK suppresses the expression and phosphorylation of FLT3 receptors and their downstream molecules. Inhibition of the NF-κB/miR-155 pathway is an important mechanism through which SHK kills FLT3-AML cells. Moreover, a low concentration of SHK promotes the differentiation of AML cells with FLT3-ITD mutations. Finally, SHK could significantly inhibit the growth of MV4-11 cells in leukemia bearing mice. CONCLUSION: The findings of this study indicate that SHK is a promising drug for the treatment of FLT3-ITD mutated AML.

Characterization and expression profiles of WUSCHEL-related homeobox (WOX) gene family in cultivated alfalfa (Medicago sativa L.).

The WUSCHEL-related homeobox (WOX) family members are plant-specific transcriptional factors, which function in meristem maintenance, embryogenesis, lateral organ development, as well as abiotic stress tolerance. In this study, 14 MsWOX transcription factors were identified and comprehensively analyzed in the cultivated alfalfa cv. Zhongmu No.1. Overall, 14 putative MsWOX members containing conserved structural regions were clustered into three clades according to phylogenetic analysis. Specific expression patterns of MsWOXs in different tissues at different levels indicated that the MsWOX genes play various roles in alfalfa. MsWUS, MsWOX3, MsWOX9, and MsWOX13-1 from the three subclades were localized in the nucleus, among which, MsWUS and MsWOX13-1 exhibited strong self-activations in yeast. In addition, various cis-acting elements related to hormone responses, plant growth, and stress responses were identified in the 3.0 kb promoter regions of MsWOXs. Expression detection of separated shoots and roots under hormones including auxin, cytokinin, GA, and ABA, as well as drought and cold stresses, showed that MsWOX genes respond to different hormones and abiotic stress treatments. Furthermore, transcript abundance of MsWOX3, and MsWOX13-2 were significantly increased after rhizobia inoculation. This study presented comprehensive data on MsWOX transcription factors and provided valuable insights into further studies of their roles in developmental processes and abiotic stress responses in alfalfa.

A Multi-Step Precision Pathway for Predicting Allograft Survival in Heterogeneous Cohorts of Kidney Transplant Recipients.

Accurate prediction of allograft survival after kidney transplantation allows early identification of at-risk recipients for adverse outcomes and initiation of preventive interventions to optimize post-transplant care. Many prediction algorithms do not model cohort heterogeneity and may lead to inaccurate assessment of longer-term graft outcomes among minority groups. Using data from a national Australian kidney transplant cohort (2008-2017) as the derivation set, we developed P-Cube, a multi-step precision prediction pathway model for predicting overall graft survival in three ethnic subgroups: European Australians, Asian Australians and Aboriginal and Torres Strait Islander Peoples. The concordance index for the European Australians, Asian Australians, and Aboriginal and Torres Strait Islander Peoples subpopulations were 0.99 (0.98-0.99), 0.93 (0.92-0.94) and 0.92 (0.91-0.93), respectively. Similar findings were observed when validating P-cube using an external dataset [Scientific Registry of Transplant Recipient Registry (2006-2020)]. Six sub-categories of recipients with distinct risk factor profiles were identified. Some factors such as blood group compatibility were considered important across the entire transplant population. Other factors such as human leukocyte antigen (HLA)-DR mismatches were unique to older recipients. The P-cube model identifies allograft survival specific risk factors within a heterogenous population and offers personalized survival predictions in a diverse cohort.

simKAP: simulation framework for the kidney allocation process with decision making model.

Organ shortage is a major barrier in transplantation and rules guarding organ allocation decisions should be robust, transparent, ethical and fair. Whilst numerous allocation strategies have been proposed, it is often unrealistic to evaluate all of them in real-life settings. Hence, the capability of conducting simulations prior to deployment is important. Here, we developed a kidney allocation simulation framework (simKAP) that aims to evaluate the allocation process and the complex clinical decision-making process of organ acceptance in kidney transplantation. Our findings have shown that incorporation of both the clinical decision-making and a dynamic wait-listing process resulted in the best agreement between the actual and simulated data in almost all scenarios. Additionally, several hypothetical risk-based allocation strategies were generated, and we found that these strategies improved recipients' long-term post-transplant patient survival and reduced wait time for transplantation. The importance of simKAP lies in its ability for policymakers in any transplant community to evaluate any proposed allocation algorithm using in-silico simulation.

TaBZR1 enhances wheat salt tolerance via promoting ABA biosynthesis and ROS scavenging.

Brassinosteroids (BRs) are vital plant steroid hormones involved in numerous aspects of plant life including growth, development, and responses to various stresses. However, the underlying mechanisms of how BR regulates abiotic stress responses in wheat (Triticum aestivum L.) remain to be elucidated. Here, we find that BR signal core transcription factor BRASSINAZOLE-RESISTANT1 (TaBZR1) is significantly up-regulated by salt treatment. Overexpression of Tabzr1-1D (a gain-of-function TaBZR1 mutant protein) improves wheat salt tolerance. Furthermore, we show that TaBZR1 binds directly to the G-box motif in the promoter of ABA biosynthesis gene TaNCED3 to activate its expression and promotes ABA accumulation. Moreover, TaBZR1 associates with the promoters of ROS-scavenging genes TaGPX2 and TaGPX3 to activate their expression. Taken together, our results elucidate that TaBZR1 improves salt-stress tolerance by activating some genes involved in the biosynthesis of ABA and ROS scavenging in wheat, which gives us a new strategy to improve the salt tolerance of wheat.

IL-24 is the key effector of Th9 cell-mediated tumor immunotherapy.

Th9 cells are powerful effector T cells for cancer immunotherapy. However, the underlying antitumor mechanism of Th9 cells still needs to be further elucidated. Here, we show that Th9 cells express high levels of not only IL-9, but also IL-24. We found that knockout of Il24 gene in Th9 cells promotes Th9 cell proliferation in vitro, but decreases Th9 cell survival in vitro and in vivo. Interestingly, knockout of Il24 gene in Th9 cells decreases the tumor-specific cytotoxicity of Th9 cells in vitro. In addition, immunotherapy with Il24 knockout Th9 cells exhibit less tumor inhibition than regular Th9 cells in mouse tumor models. We found that inhibition of Foxo1 by a specific inhibitor downregulates IL-24 expression in Th9 cells and decreases Th9 cell antitumor efficacy in vivo. Our results identify IL-24 as a powerful antitumor effector of Th9 cells and provide a target in Th9 cell-mediated tumor therapy.