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.

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.

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.

Retracted memories in the general population: are there differences between eastern and western countries?

The main purpose of the current studies was to examine retracted experiences in the general population from various cultural backgrounds. More specifically, in two studies, we examined the details of memory retraction experiences, the reasons for retraction, and the outcomes of retraction in participants from China and other countries, mainly the United States of America. It was found that memory retraction experiences appeared to be quite common. In the sample of Chinese participants (Study 1: N = 1380), 50.58% reported at least one such an experience, whereas in respondents from other countries (Study 2; N = 425), a significantly lower but still substantial prevalence rate of 35% was found. In general, the retracted memories predominantly involved positive events and some respondents experienced pressure during the withdrawal. Social feedback and event plausibility were the two main reasons for the withdrawal. Compared to recollection scores, belief scores decreased significantly after withdrawal, and some respondents even formed nonbelieved memories. After retracting the memories, most respondents felt they gained benefits (e.g., they had resolved a psychological problem that had bothered them for years). These studies give us a more general understanding of retracted memory experiences in the general population.

Peri-lesion regions in differentiating suspicious breast calcification-only lesions specifically on contrast enhanced mammography.

PURPOSE: The explore the added value of peri-calcification regions on contrast-enhanced mammography (CEM) in the differential diagnosis of breast lesions presenting as only calcification on routine mammogram. METHODS: Patients who underwent CEM because of suspicious calcification-only lesions were included. The test set included patients between March 2017 and March 2019, while the validation set was collected between April 2019 and October 2019. The calcifications were automatically detected and grouped by a machine learning-based computer-aided system. In addition to extracting radiomic features on both low-energy (LE) and recombined (RC) images from the calcification areas, the peri-calcification regions, which is generated by extending the annotation margin radially with gradients from 1 mm to 9 mm, were attempted. Machine learning (ML) models were built to classify calcifications into malignant and benign groups. The diagnostic matrices were also evaluated by combing ML models with subjective reading. RESULTS: Models for LE (significant features: wavelet-LLL_glcm_Imc2_MLO; wavelet-HLL_firstorder_Entropy_MLO; wavelet-LHH_glcm_DifferenceVariance_CC; wavelet-HLL_glcm_SumEntropy_MLO;wavelet-HLH_glrlm_ShortRunLowGray LevelEmphasis_MLO; original_firstorder_Entropy_MLO; original_shape_Elongation_MLO) and RC (significant features: wavelet-HLH_glszm_GrayLevelNonUniformityNormalized_MLO; wavelet-LLH_firstorder_10Percentile_CC; original_firstorder_Maximum_MLO; wavelet-HHH_glcm_Autocorrelation_MLO; original_shape_Elongation_MLO; wavelet-LHL_glszm_GrayLevelNonUniformityNormalized_MLO; wavelet-LLH_firstorder_RootMeanSquared_MLO) images were set up with 7 features. Areas under the curve (AUCs) of RC models are significantly better than those of LE models with compact and expanded boundary (RC v.s. LE, compact: 0.81 v.s. 0.73, p < 0.05; expanded: 0.89 v.s. 0.81, p < 0.05) and RC models with 3 mm boundary extension yielded the best performance compared to those with other sizes (AUC = 0.89). Combining with radiologists' reading, the 3mm-boundary RC model achieved a sensitivity of 0.871 and negative predictive value of 0.937 with similar accuracy of 0.843 in predicting malignancy. CONCLUSIONS: The machine learning model integrating intra- and peri-calcification regions on CEM has the potential to aid radiologists' performance in predicting malignancy of suspicious breast calcifications.

VvWRKY5 positively regulates wounding-induced anthocyanin accumulation in grape by interplaying with VvMYBA1 and promoting jasmonic acid biosynthesis.

Wounding stress induces the biosynthesis of various secondary metabolites in plants, including anthocyanin. However, the underlying molecular mechanism remains elusive. Here, we reported that a transcription factor, VvWRKY5, promotes wounding-induced anthocyanin accumulation in grape (Vitis vinifera). Biochemical and molecular analyses demonstrated that wounding stress significantly increased anthocyanin content, and VvMYBA1 plays an essential role in this process. VvWRKY5 could interact with VvMYBA1 and amplify the activation effect of VvMYBA1 on its target gene VvUFGT. The transcript level of VvWRKY5 was notably induced by wounding treatment. Moreover, our data demonstrated that VvWRKY5 could promote the synthesis of jasmonic acid (JA), a phytohormone that acts as a positive modulator in anthocyanin accumulation, by directly binding to the W-box element in the promoter of the JA biosynthesis-related gene VvLOX and enhancing its activities, and this activation was greatly enhanced by the VvWRKY5-VvMYBA1 protein complex. Collectively, our findings show that VvWRKY5 plays crucial roles in wounding-induced anthocyanin synthesis in grape and elucidates the transcriptional regulatory mechanism of wounding-induced anthocyanin accumulation.

The Relationship Between Chromosomal Polymorphism and Male Reproductive Abnormalities.

This study aims to investigate the association between chromosomal polymorphisms and abnormalities in male reproductive health. Within the period from January 2018 to December 2022, a cohort of 10,827 males seeking fertility services at our reproductive center was selected for inclusion in this study. Peripheral blood chromosomal karyotype analysis was conducted for each participant to identify carriers of chromosomal polymorphisms, who were subsequently categorized into a polymorphism group. Additionally, a control group was constituted by randomly selecting 1,630 patients exhibiting normal chromosomal karyotypes. The study conducted statistical analyses to compare clinical outcomes between the two groups, focusing on infertility, history of spontaneous miscarriage in partners, anomalies in reproductive development, fetal abnormalities, and sperm quality metrics. (1) Among the cohort of 10,827 males, chromosomal polymorphisms were identified in 1,622 participants, yielding a detection rate of 14.98%. This rate is significantly elevated in comparison to the baseline prevalence of 1.77% observed in the general population. (2) The predominant variant among these polymorphisms was related to the Y chromosome, accounting for 1,082 cases (66.71% of the polymorphic findings), corresponding to a detection rate of 9.99%. This is markedly higher than the approximate 0.09% prevalence noted within a normative demographic. (3) Statistical analysis revealed significant disparities between the chromosomal polymorphism group and the control group in several clinical outcomes. Notably, the rates of spontaneous abortion (18.06% vs. 1.35%), fetal anomalies (1.97% vs. 0.25%), and poor sperm quality (41.74% vs. 7.18%) were markedly higher in the polymorphism group. Additionally, incidences of testicular dysgenesis (2.28% vs. 0.92%) and hypogonadism in partners (0.62% vs. 0.37%) also demonstrated significant differences, underscoring the potential reproductive implications of chromosomal polymorphisms. The study establishes a significant link between chromosomal polymorphisms and critical reproductive outcomes, including male infertility, spontaneous miscarriages in partners, fetal anomalies, and reduced sperm quality. These findings highlight the clinical relevance of chromosomal polymorphisms in reproductive health assessments and suggest the necessity for their consideration in the diagnostic and therapeutic strategies for male reproductive disorders.

Analysis of the chain-mediated effects of nurses' sense of professional gain and sense of professional mission between psychological resilience and work engagement in 10 general hospitals in Sichuan province.

Objective: To explore the chain-mediated role of sense of career benefit and sense of career mission in the mechanism of psychological flexibility's effect on nurses' work engagement. Methods: Adopting the convenience sampling method, 1032 nurses in 10 general hospitals in Sichuan Province were surveyed by questionnaires using the General Information Questionnaire, Sense of Occupational Benefit Scale, Sense of Occupational Mission Scale, Psychological Flexibility Scale, and work engagement Scale in August-October 2022, and the model of the chained-mediated effect was constructed and validated. Results: The total psychological resilience score of nurses in 10 general hospitals in Sichuan Province was (91.29 ± 17.38), the total score of sense of occupational benefit was (137.85 ± 21.02), the total score of sense of occupational mission was (40.27 ± 7.37), and the total score of work engagement was (34.99 ± 9.80). The total score of nurses' work engagement was positively correlated with the total scores of psychological elasticity, sense of professional benefit, and sense of professional mission (all P < 0.05). The direct effect of psychological elasticity on nurses' work engagement was significant, with an effect value of 0.321; the chain mediation effects of occupational benefit and occupational mission as separate mediators and the chain mediation effects of the two were 0.039, 0.032, and 0.062, respectively. Conclusion: Nurses' work engagement in 10 general hospitals in Sichuan province is at a medium level, and occupational benefit and occupational mission play a significant role in the mechanism of the psychological elasticity's effects on nurses' work commitment, and the chain mediation effect of occupational mission in the mechanism of psychological elasticity is established. The chain mediation effect in the mechanism was established. Managers should pay attention to nurses with low psychological elasticity, improve their sense of occupational benefit, and enhance their sense of occupational mission in order to further promote the enhancement of work engagement.

Edge-relational window-attentional graph neural network for gene expression prediction in spatial transcriptomics analysis.

Spatial transcriptomics (ST), containing gene expression with fine-grained (i.e., different windows) spatial location within tissue samples, has become vital in developing innovative treatments. Traditional ST technology, however, rely on costly specialized commercial equipment. Addressing this, our article aims to creates a cost-effective, virtual ST approach using standard tissue images for gene expression prediction, eliminating the need for expensive equipment. Conventional approaches in this field often overlook the long-distance spatial dependencies between different sample windows or need prior gene expression data. To overcome these limitations, we propose the Edge-Relational Window-Attentional Network (ErwaNet), enhancing gene prediction by capturing both local interactions and global structural information from tissue images, without prior gene expression data. ErwaNet innovatively constructs heterogeneous graphs to model local window interactions and incorporates an attention mechanism for global information analysis. This dual framework not only provides a cost-effective solution for gene expression predictions but also obviates the necessity of prior knowledge gene expression information, a significant advantage in the field of cancer research where it enables a more efficient and accessible analytical paradigm. ErwaNet stands out as a prior-free and easy-to-implement Graph Convolution Network (GCN) method for predicting gene expression from tissue images. Evaluation of the two public breast cancer datasets shows that ErwaNet, without additional information, outperforms the state-of-the-art (SOTA) methods. Code is available at https://github.com/biyecc/ErwaNet.

Efficacy of probiotics or synbiotics in critically ill patients: A systematic review and meta-analysis.

BACKGROUND: This latest systematic review and meta-analysis aim to examine the effects of probiotic and synbiotic supplementation in critically ill patients. METHODS: Relevant articles were retrieved from PubMed, Embase, the Cochrane Database, and the Web of Science. The primary output measure was the incident of ventilator-associated pneumonia, and the secondary outputs were diarrhea, Clostridium diffusion infection (CDI), incident of sepsis, incident of hospital acquired pneumonia, duration of mechanical exploitation, ICU mortality rate, length of ICU stay, in hospital mortality, and length of hospital stay. Data were pooled and expressed as Relative Risk(RR) and Standardized Mean Difference (SMD) with a 95 % confidence interval (CI). RESULTS: 33 studies were included in this systematic review and meta-analysis, with 4065 patients who received probiotics or synbiotics (treatment group) and 3821 patients who received standard care or placebo (control group). The pooled data from all included studies demonstrated that the treatment group has significantly reduced incidence of ventilation-associated pneumonia (VAP) (RR = 0.80; 95 % CI: 0.67-0.96; p = 0.021, I2 = 52.5 %) and sepsis (RR = 0.97; 95 % CI: 0.66-1.42; p = 0.032, I2 = 54.4 %), As well as significantly increased duration of mechanical exploitation (SMD = -0.47; 95 % CI: -0.74-0.20, p = 0.012, I2 = 63.4 %), ICU mobility (RR = 0.95; 95 % CI: 0.71-1.27; p = 0.004, I2 = 62.8 %), length of ICU stay (SMD = -0.29; 95 % CI: -0.58-0.01; p = 0.000, I2 = 82.3 %) and length of hospital stay (SMD = -0.33; 95 % CI: -0.57-0.08, p = 0.000, I2 = 74.2 %) than the control group. There were no significant differences in diarrhea, CDI, incidence of hospital acquired pneumonia, and in hospital mortality between the two groups. CONCLUSION: Our meta-analysis showed that probiotic and synbiotic supplements are beneficial for critically ill patients as they significantly reduce the incidence of ventilator associated pneumonia and sepsis, as well as the duration of mechanical exploitation, length of hospital stay, length of ICU stay, and ICU mortality. However, this intervention has minimal impact on diarrhea, CDI, incidence of hospital acquired pneumonia, and in hospital mortality in critically ill patients.

Doxercalciferol alleviates UVB-induced HaCaT cell senescence and skin photoaging.

Prolonged or excessive ultraviolet (UV) exposure can lead to premature skin aging. Doxercalciferol (Dox), an analog of vitamin D2, is chiefly used to treat endocrine diseases, cardiovascular diseases, kidney diseases, etc. To date, research on Dox in alleviating photoaging and UV-induced inflammation is scarce. In this research, we evaluated the function of Dox in ultraviolet radiation B (UVB)-induced photoaging and explored the potential mechanism in human keratinocytes (Hacat) and BALB/c mice. First, we established a stable UVB-induced photoaging cell model. Then, we found that the senescence ß-galactosidase (SA-ß-Gal) positive rate, senescence-related protein (p16), aging-related genes (p21 and p53), senescence-associated secretory phenotype (SASP), inflammatory driving factors (IL-1ß and IL-6) and matrix metalloproteinases (MMPs) (MMP1 and MMP9) were upregulated in HaCaT cells after UVB irradiation. At the same time, the effect of UVB on the back skin of BALB/c mice showed a consistent trend. Dox effectively alleviated the aforementioned changes caused by UVB radiation. Mechanistically, we found that UVB activated mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) signaling pathways, and Dox inhibited UVB-activated NF-κB and MAPK. Furthermore, Dox inhibited UVB-induced skin photoaging and damage in mice. In summary, Dox has been improved to inhibit photoaging, which may help to develop therapies to delay skin photoaging.

N-glycan biosignatures as a potential diagnostic biomarker for early-stage pancreatic cancer.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, with a 5-year survival rate of less than 10%, owing to its late-stage diagnosis. Early detection of pancreatic cancer (PC) can significantly increase survival rates. AIM: To identify the serum biomarker signatures associated with early-stage PDAC by serum N-glycan analysis. METHODS: An extensive patient cohort was used to determine a biomarker signature, including patients with PDAC that was well-defined at an early stage (stages I and II). The biomarker signature was derived from a case-control study using a case-cohort design consisting of 29 patients with stage I, 22 with stage II, 4 with stage III, 16 with stage IV PDAC, and 88 controls. We used multiparametric analysis to identify early-stage PDAC N-glycan signatures and developed an N-glycan signature-based diagnosis model called the "Glyco-model". RESULTS: The biomarker signature was created to discriminate samples derived from patients with PC from those of controls, with a receiver operating characteristic area under the curve of 0.86. In addition, the biomarker signature combined with cancer antigen 19-9 could discriminate patients with PDAC from controls, with a receiver operating characteristic area under the curve of 0.919. Glyco-model demonstrated favorable diagnostic performance in all stages of PC. The diagnostic sensitivity for stage I PDAC was 89.66%. CONCLUSION: In a prospective validation study, this serum biomarker signature may offer a viable method for detecting early-stage PDAC.

The value of right ventricular pulmonary artery coupling in determining the prognosis of patients with sepsis.

The outcomes of patients with sepsis are influenced by the contractile function of the right ventricle (RV), but the impact of cardiopulmonary interaction in ICU-mortality of sepsis patients remains unclear. This study aims to investigate the ICU-mortality impact of right ventricular-pulmonary artery (RV-PA) coupling in patients with sepsis. We employed echocardiography to assess patients with sepsis within the initial 24 h of their admission to the ICU. RV-PA coupling was evaluated using the tricuspid annular plane systolic excursion (TAPSE) to pulmonary artery systolic pressure (PASP) ratio. A total of 92 subjects were enrolled, with 55 survivors and 37 non-survivors. TAPSE/PASP ratio assessed mortality with an area under the curve (AUC) of 0.766 (95% CI 0.670-0.862) and the optimal cutoff value was 0.495 mm/mmHg. We constructed a nomogram depicting the TAPSE/PASP in conjunction with IL-6 and Lac for the joint prediction of sepsis prognosis, and demonstrated the highest predictive capability (AUC = 0.878, 95% CI 0.809-0.948). In conclusion, the TAPSE/PASP ratio demonstrated prognostic value for ICU mortality in sepsis patients. The nomogram, which combines the TAPSE/PASP, IL-6, and LAC, demonstrated enhanced predictive efficacy for the prognosis of sepsis patients.

Dasabuvir alleviates 5-fluorouracil-induced intestinal injury through anti-senescence and anti-inflammatory.

5-Fluorouracil (5-Fu) is a basic drug that is used to treat colorectal cancer. Patients who receive 5-Fu chemotherapy often experience side effects that affect the digestive system, such as intestinal injury and diarrhoea, which significantly affect patient compliance with anticancer treatment and quality of life. Therefore, identifying approaches to treat or prevent these side effects is urgent. Dasabuvir (DSV) is a hepatitis C virus inhibitor, but its impact on 5-Fu-induced intestinal injury remains unknown. Our study investigated the effects of DSV on 5-Fu-induced intestinal injury in HUVECs, HIECs and male BALB/c mice. We found that 5-Fu caused intestinal damage by inducing senescence, increasing inflammatory factor expression, and generating oxidative stress. Compared with 5-Fu treatment alone, DSV inhibited senescence by reducing senescence-ß-galactosidase (SA-ß-gal) activity, the senescence-associated secretory phenotype (SASP, including IL-1, IL-6, and TNF-α) and senescence marker expression levels (p16, p21, and p53). Moreover, the anti-senescence effect of DSV was achieved by inhibiting the mTOR signaling pathway. DSV increased antioxidant enzyme levels and alleviated intestinal tissue injury in mice. In addition, DSV suppressed the 5-Fu-induced increase the diarrhoea scores and ameliorated the weight loss, food intake and water intake of the mice. Overall, this study indicated that DSV could be used to treat chemotherapy-induced intestinal damage.