MdMYB44-like positively regulates salt and drought tolerance via the MdPYL8-MdPP2CA module in apple.

Abscisic acid (ABA) is involved in salt and drought stress responses, but the underlying molecular mechanism remains unclear. Here, we demonstrated that the overexpression of MdMYB44-like, an R2R3-MYB transcription factor, significantly increases the salt and drought tolerance of transgenic apples and Arabidopsis. MdMYB44-like inhibits the transcription of MdPP2CA, which encodes a type 2C protein phosphatase that acts as a negative regulator in the ABA response, thereby enhancing ABA signaling-mediated salt and drought tolerance. Furthermore, we found that MdMYB44-like and MdPYL8, an ABA receptor, form a protein complex that further enhances the transcriptional inhibition of the MdPP2CA promoter by MdMYB44-like. Significantly, we discovered that MdPP2CA can interfere with the physical association between MdMYB44-like and MdPYL8 in the presence of ABA, partially blocking the inhibitory effect of the MdMYB44-like-MdPYL8 complex on the MdPP2CA promoter. Thus, MdMYB44-like, MdPYL8, and MdPP2CA form a regulatory loop that tightly modulates ABA signaling homeostasis under salt and drought stress. Our data reveal that MdMYB44-like precisely modulates ABA-mediated salt and drought tolerance in apples through the MdPYL8-MdPP2CA module.

The MdIAA29-MdARF4 complex plays an important role in balancing plant height with salt and drought stress responses.

Breeding dwarf apple (Malus domestica) varieties is a recent trend in agriculture because such varieties are easy to maintain and have high yields; however, dwarf apple trees generally have poor stress tolerance. Balancing apple plant height and stress response has been an important breeding goal. In this study, aux/indole-3-acetic acid 29 gene in apple (MdIAA29) overexpression lines (#1, #2, #3) had reduced plant height by 39%, 31%, and 35%, respectively, suitable for close planting applications. Surprisingly, the dwarf MdIAA29-overexpression lines also showed increased plant tolerance to salt and drought stresses. Further analysis showed that MdIAA29 inhibited the regulation of auxin response factor 4 (ARF4) on Gretchen Hagen 3.9 (GH3.9) gene and 9-cis-epoxycarotenoid dioxygenase 3 (NCED3) gene in apple and changed the contents of auxin and abscisic acid in different tissues, thus achieving a balance between plant height and stress tolerance. In addition, we also found that MdIAA7 enhanced the inhibitory effect of MdIAA29 on MdARF4. In brief, the MdIAA29-MdARF4 complex significantly impacts the height of apple plants and their ability to respond to salt and drought stress.

Observation of In-Gap States in a Two-Dimensional CrI2/NbSe2 Heterostructure.

Low-dimensional magnetic structures coupled with superconductors are promising platforms for realizing Majorana zero modes, which have potential applications in topological quantum computing. Here, we report a two-dimensional (2D) magnetic-superconducting heterostructure consisting of single-layer chromium diiodide (CrI2) on a niobium diselenide (NbSe2) superconductor. Single-layer CrI2 nanosheets, which hold antiferromagnetic (AFM) ground states by our first-principles calculations, were epitaxially grown on the layered NbSe2 substrate. Using scanning tunneling microscopy/spectroscopy, we observed robust in-gap states spatially located at the edge of the nanosheets and defect-induced zero-energy peaks inside the CrI2 nanosheets. Magnetic-flux vortices induced by an external field exhibit broken 3-fold rotational symmetry of the pristine NbSe2 superconductor, implying the efficient modulation of the interfacial superconducting states by the epitaxial CrI2 layer. A phenomenological model suggests the existence of chiral edge states in a 2D AFM-superconducting hybrid system with an even Chern number, providing a qualitatively plausible understanding for our experimental observation.

Machine learning models for predicting of PD-1 treatment efficacy in Pan-cancer patients based on routine hematologic and biochemical parameters.

Immune checkpoint blockade therapy targeting the programmed death-1(PD-1) pathway has shown remarkable efficacy and durable response in patients with various cancer types. Early prediction of therapeutic efficacy is important for optimizing treatment plans and avoiding potential side effects. In this work, we developed an efficient machine learning prediction method using routine hematologic and biochemical parameters to predict the efficacy of PD-1 combination treatment in Pan-Cancer patients. A total of 431 patients with nasopharyngeal carcinoma, esophageal cancer and lung cancer who underwent PD-1 checkpoint inhibitor combination therapy were included in this study. Patients were divided into two groups: progressive disease (PD) and disease control (DC) groups. Hematologic and biochemical parameters were collected before and at the third week of PD-1 therapy. Six machine learning models were developed and trained to predict the efficacy of PD-1 combination therapy at 8-12 weeks. Analysis of 57 blood biomarkers before and after three weeks of PD-1 combination therapy through statistical analysis, heatmaps, and principal component analysis did not accurately predict treatment outcome. However, with machine learning models, both the AdaBoost classifier and GBDT demonstrated high levels of prediction efficiency, with clinically acceptable AUC values exceeding 0.7. The AdaBoost classifier exhibited the highest performance among the 6 machine learning models, with a sensitivity of 0.85 and a specificity of 0.79. Our study demonstrated the potential of machine learning to predict the efficacy of PD-1 combination therapy based on changes in hematologic and biochemical parameters.

Parallel CNN-Deep Learning Clinical-Imaging Signature for Assessing Pathologic Grade and Prognosis of Soft Tissue Sarcoma Patients.

BACKGROUND: Traditional biopsies pose risks and may not accurately reflect soft tissue sarcoma (STS) heterogeneity. MRI provides a noninvasive, comprehensive alternative. PURPOSE: To assess the diagnostic accuracy of histological grading and prognosis in STS patients when integrating clinical-imaging parameters with deep learning (DL) features from preoperative MR images. STUDY TYPE: Retrospective/prospective. POPULATION: 354 pathologically confirmed STS patients (226 low-grade, 128 high-grade) from three hospitals and the Cancer Imaging Archive (TCIA), divided into training (n = 185), external test (n = 125), and TCIA cohorts (n = 44). 12 patients (6 low-grade, 6 high-grade) were enrolled into prospective validation cohort. FIELD STRENGTH/SEQUENCE: 1.5 T and 3.0 T/Unenhanced T1-weighted and fat-suppressed-T2-weighted. ASSESSMENT: DL features were extracted from MR images using a parallel ResNet-18 model to construct DL signature. Clinical-imaging characteristics included age, gender, tumor-node-metastasis stage and MRI semantic features (depth, number, heterogeneity at T1WI/FS-T2WI, necrosis, and peritumoral edema). Logistic regression analysis identified significant risk factors for the clinical model. A DL clinical-imaging signature (DLCS) was constructed by incorporating DL signature with risk factors, evaluated for risk stratification, and assessed for progression-free survival (PFS) in retrospective cohorts, with an average follow-up of 23 ± 22 months. STATISTICAL TESTS: Logistic regression, Cox regression, Kaplan-Meier curves, log-rank test, area under the receiver operating characteristic curve (AUC)，and decision curve analysis. A P-value <0.05 was considered significant. RESULTS: The AUC values for DLCS in the external test, TCIA, and prospective test cohorts (0.834, 0.838, 0.819) were superior to clinical model (0.662, 0.685, 0.694). Decision curve analysis showed that the DLCS model provided greater clinical net benefit over the DL and clinical models. Also, the DLCS model was able to risk-stratify patients and assess PFS. DATA CONCLUSION: The DLCS exhibited strong capabilities in histological grading and prognosis assessment for STS patients, and may have potential to aid in the formulation of personalized treatment plans. TECHNICAL EFFICACY: Stage 2.

Prevalence and risk factors of fatigue and its association with quality of life among patients with chronic pancreatitis: A cross-sectional study.

BACKGROUND: Fatigue is a debilitating symptom found in various chronic diseases and is associated with more severe symptoms and worse quality of life (QoL). However, this symptom has not been adequately addressed in chronic pancreatitis (CP), and there have been no studies on fatigue in patients with CP. METHODS: This cross-sectional study was conducted at the Changhai Hospital in Shanghai, China. Data on the patients' sociodemographic, disease, and therapeutic characteristics were collected. Fatigue was assessed using the Multidimensional Fatigue Inventory-20. QoL was assessed utilizing the European Organization for the Research and Treatment of Cancer of QoL questionnaire (EORTC-QLQ-C30). Sleep quality, anxiety and depression, and pain was assessed using Pittsburgh Sleep Quality Index, the Hospital Anxiety and Depression Scale, and the Brief Pain Inventory, respectively. RESULTS: The prevalence of fatigue among Chinese patients with CP was 35.51 % (87/245). Multivariate analysis showed that steatorrhea (OR = 2.638, 95 % CI: 1.117-6.234), history of smoking (OR = 4.627, 95 % CI: 1.202-17.802), history of endoscopic treatment (OR = 0.419, 95 % CI: 0.185-0.950), depression (OR = 5.924, 95 % CI: 2.462-14.255), and sleep disorder (OR = 6.184, 95 % CI: 2.543-15.034) were influencing factors for the presence of fatigue. The scores for global health and all functional dimensions in the EORTC-QLQ-C30 significantly decreased, whereas the scores for all symptom dimensions significantly increased in patients with fatigue. CONCLUSIONS: This study indicated that Fatigue is a common symptom and has a negative impact on the QoL of patients with CP. Steatorrhea, smoking history, endoscopic treatment, depression, and sleep disorders were associated with fatigue.

TMSCN-Promoted Difunctionalization of Alkenes for the Synthesis of Alcohol Derivatives.

A TMSCN-promoted difunctionalization of styrenes with CHCl3 and TBHP is reported via the radical addition/cross coupling process. A wide range of dichloromethyl-substituted alcohol derivatives were synthesized under transition-metal-free conditions. Besides, this method is also applicable to unactive alkenes. The key to this success lies in the role of TMSCN, which prevents the reaction toward dichloromethylperoxylation of olefins. This represents an alternative approach for synthesizing diverse alcohol derivatives using readily available substrates, holding significant promise in the fields of pharmaceutical chemistry and natural product synthesis.

DRP1 knockdown and atorvastatin alleviate ox-LDL-induced vascular endothelial cells injury: DRP1 is a potential target for preventing atherosclerosis.

Vascular endothelial cells (VECs) injury is the first step in the pathogenesis of atherosclerosis (AS). Mitochondrial dysfunction plays a significant role in VECs injury, but the underlying mechanisms are still unclear. Here, the human umbilical vein endothelial cells were exposed to 100 µg/mL oxidized low-density lipoprotein for 24 h to establish AS model in vitro. We reported that mitochondrial dynamics disorder is a prominent feature of VECs in AS models and associated with mitochondrial dysfunction. Moreover, the knockdown of dynamin-related protein 1 (DRP1) in AS model significantly alleviated the mitochondrial dynamics disorder and VECs injury. On the contrary, DRP1 overexpression significantly aggravated this injury. Interestingly, atorvastatin (ATV), a classical anti-atherosclerotic drug, prominently inhibited the expression of DRP1 in AS models and similarly alleviated the mitochondrial dynamics disorder and VECs injury in vitro and in vivo. At the same time, we found that ATV alleviated VECs damage but did not significantly reduce lipid concentration in vivo. Our findings provide a potential therapeutic target of AS and a new mechanism of the anti-atherosclerotic effect of ATV.

Impact of Lifestyle on Urinary Incontinence Severity among Women: A Cross-Sectional Study in East China.

INTRODUCTION AND HYPOTHESIS: Identifying the factors influencing the development of female urinary incontinence (UI) may facilitate early intervention, potentially delaying its progression. This study was aimed at investigating the impact of lifestyle habits on the severity of UI among women in East China. METHODS: This study included 414 women from six communities in East China who reported symptoms of UI and was conducted between September and December 2020. Data were collected using a general information questionnaire, the Toileting Behaviours: Women's Elimination Behaviours scale, and the International Consultation on Incontinence Questionnaire Urinary Incontinence Short Form Chinese Version. Participants were categorised into two groups: those with mild UI and those with moderate-to-severe UI. Propensity-score matching was performed to balance confounding factors, and logistic regression was used to explore the relationship between lifestyle behaviours and UI severity. RESULTS: A total of 117 pairs were successfully matched. Logistic regression analysis revealed that daily perineal cleaning significantly protected against moderate-to-severe UI (p < 0.05). Conversely, living alone, poor sleep quality and hovering over the toilet while voiding were identified as independent risk factors for moderate-to-severe UI (p < 0.05). CONCLUSION: Several lifestyle habits significantly impact the severity of UI among adult women. Screening for mild urinary leakage symptoms and implementing timely interventions are crucial for preventing the aggravation of UI and improving ability to work and quality of life.

The transcription factor MdERF023 negatively regulates salt tolerance by modulating ABA signaling and Na+/H+ transport in apple.

KEY MESSAGE: MdERF023 is a transcription factor that can reduce salt tolerance by inhibiting ABA signaling and Na+/H+ homeostasis. Salt stress is one of the principal environmental stresses limiting the growth and productivity of apple (Malus × domestica). The APETALA2/ethylene response factor (AP2/ERF) family plays key roles in plant growth and various stress responses; however, the regulatory mechanism involved has not been fully elucidated. In the present study, we identified an AP2/ERF transcription factor (TF), MdERF023, which plays a negative role in apple salt tolerance. Stable overexpression of MdERF023 in apple plants and calli significantly decreased salt tolerance. Biochemical and molecular analyses revealed that MdERF023 directly binds to the promoter of MdMYB44-like, a positive modulator of ABA signaling-mediated salt tolerance, and suppresses its transcription. In addition, MdERF023 downregulated the transcription of MdSOS2 and MdAKT1, thereby reducing the Na+ expulsion, K+ absorption, and salt tolerance of apple plants. Taken together, these results suggest that MdERF023 reduces apple salt tolerance by inhibiting ABA signaling and ion transport, and that it could be used as a potential target for breeding new varieties of salt-tolerant apple plants via genetic engineering.