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.

Compare deep learning model and conventional logistic regression model for the identification of unstable saccular intracranial aneurysms in computed tomography angiography.

Background: It is crucial to distinguish unstable from stable intracranial aneurysms (IAs) as early as possible to derive optimal clinical decision-making for further treatment or follow-up. The aim of this study was to investigate the value of a deep learning model (DLM) in identifying unstable IAs from computed tomography angiography (CTA) images and to compare its discriminatory ability with that of a conventional logistic regression model (LRM). Methods: From August 2011 to May 2021, a total of 1,049 patients with 681 unstable IAs and 556 stable IAs were retrospectively analyzed. IAs were randomly divided into training (64%), internal validation (16%), and test sets (20%). Convolutional neural network (CNN) analysis and conventional logistic regression (LR) were used to predict which IAs were unstable. The area under the curve (AUC), sensitivity, specificity and accuracy were calculated to evaluate the discriminating ability of the models. One hundred and ninety-seven patients with 229 IAs from Banan Hospital were used for external validation sets. Results: The conventional LRM showed 11 unstable risk factors, including clinical and IA characteristics. The LRM had an AUC of 0.963 [95% confidence interval (CI): 0.941-0.986], a sensitivity, specificity and accuracy on the external validation set of 0.922, 0.906, and 0.913, respectively, in predicting unstable IAs. In predicting unstable IAs, the DLM had an AUC of 0.771 (95% CI: 0.582-0.960), a sensitivity, specificity and accuracy on the external validation set of 0.694, 0.929, and 0.782, respectively. Conclusions: The CNN-based DLM applied to CTA images did not outperform the conventional LRM in predicting unstable IAs. The patient clinical and IA morphological parameters remain critical factors for ensuring IA stability. Further studies are needed to enhance the diagnostic accuracy.

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.

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.

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.

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.

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.

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.

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.

Development and validation of a nomogram to predict hypothermia in adult burn patients during escharectomy under general anesthesia.

BACKGROUND: It is very common for burn patients to have hypothermia during escharectomy under general anesthesia, which increases the blood transfusion demand of burn patients, and may lead to blood coagulation disorder or even increase the mortality of patients. It is important to predict the occurrence of hypothermia in advance, but we lack a prognostic prediction model. Our study aimed to develop a nomogram to predict the incidence of hypothermia in adult burn patients undergoing escharectomy under general anesthesia to intervention the hazards associated with hypothermia early. METHODS: This retrospective study included 978 adult burn patients who underwent simple escharectomy under general anesthesia during hospitalization between January 2017 and December 2022, they were further divided into a training cohort and a validation cohort. The clinical data were recorded in electronic medical record system and a self-made collection table of intraoperative hypothermia. The preliminary predictive factors for hypothermia which undergoing simple escharectomy under general anesthesia in burn patients were determined using least absolute shrinkage and selection operator (LASSO) at first, then the final predictive factors determined using binary logistic regression analyses and a nomogram to predict the occurrence of hypothermia was established. The index of concordance(C-index), calibration curves, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA) were used to evaluate the performance of the model. RESULTS: A total of 211 patients with hypothermia and 767 patients without hypothermia were selected. Least absolute shrinkage and selection operator regression analysis and binary logistic regression results concluded that burn index, urinary volume, blood transfusion volume and irrigation volume were significantly associated with hypothermia in burn patients undergoing escharectomy under general anesthesia. The nomogram based on these four variables had good predictive efficiency for hypothermia in adult burn patients during escharectomy under general anesthesia, the C-index in the training cohort was 0.903, areas under the receiver operating characteristic curves (AUROC) of for the training cohort (95 % CI 0.877-0.920) and 0.875 for the validation cohort (95 % CI 0.852-0.897) indicated satisfactory discriminative ability of the nomogram, and the calibration curves for the training cohort and the validation cohort also fit as well, indicating that the nomogram had good clinical application value. CONCLUSIONS: Hypothermia in burn patients during escharectomy under general anesthesia is associated with burn index, urinary volume, blood transfusion volume and irrigation volume. We successfully developed a practical nomogram to accurately predict hypothermia, which is a practical method helping clinicians rapidly and conveniently diagnose and guide the treatment of hypothermia in burn patients during escharectomy under general anesthesia.

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.

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.

[Quality evaluation of Lysimachiae Herba from different habitats based on simultaneous determination of multiple bioactive constituents combined with multivariate statistical analysis].

A method based on ultra-high performance liquid chromatography coupled with triple quadrupole linear ion trap-tandem mass spectrometry(UHPLC-QTRAP-MS/MS) was developed for the simultaneous determination of 41 bioactive constituents of flavonoids, organic acids, nucleosides, and amino acids in Lysimachiae Herba. The content of multiple bioactive constituents was compared among the samples from different habitats. The chromatographic separation was performed in a Waters XBridge®C_(18) column(4.6 mm×100 mm, 3.5 µm) at 30 ℃. The gradient elution was performed with 0.4% methanol(A)-formic acid water(B) as the mobile phase at a flow rate of 0.8 mL·min~(-1), and the multiple-reaction monitoring(MRM) mode was adopted. According to the content of 41 constituents, hierarchical cluster analysis(HCA), orthogonal partial least squares discriminant analysis(OPLS-DA), and gray relational analysis(GRA) were perfomed to comprehensively evaluate the samples from different habitats. The results showed that the 41 constituents exhibited good linear relationship within the tested concentration ranges, with the correlation coefficients(r) greater than 0.999 4. The method featured good precision, repeatability, and stability with the relative standard deviations(RSDs) less than 5.0%. The average recoveries of the 41 constituents ranged from 98.06% to 101.9%, with the RSDs of 0.62%-4.6%. HCA and OPLS-DA separated 48 batches of Lysimachiae Herba samples from different habitats into three categories: the producing areas in Sichuan and Chongqing, the producing areas in Jiangsu, Zhejiang, and Jiangxi, and the producing areas in Guizhou. The content of 41 constituents varied among the Lysimachiae Herba samples from different habitats. The GRA results revealed that the Lysimachiae Herba sample from Nanchong City, Sichuan Province had the best comprehensive quality. The method developed in this study was accurate and reliable and thus can be used for comprehensive evaluation of Lysimachiae Herba quality and provide basic information for the selection of habitats.

Confusing finding of quantitative fluorescent polymerase chain reaction analysis in invasive prenatal genetic diagnosis: A case report.

BACKGROUND: Quantitative fluorescent polymerase chain reaction (QF-PCR) is a rapid prenatal diagnostic method for abnormalities on chromosomes 21, 18, and 13 and sex chromosomal aneuploidy. However, the value of QF-PCR in diagnosing chromosomal structural abnormalities is limited. In this article, we report a confusing QF-PCR finding in a pregnant woman who underwent amniocentesis. CASE SUMMARY: The short tandem repeat marker AMXY (Xp22.2/Yp11.2) located on the sex chromosome exhibited a trisomic biallelic pattern, indicating that the karyotype of the fetus might be 47,XYY. Chromosome analysis performed on cultured amniocytes showed a normal male karyotype of the fetus. Copy number variation sequencing confirmed a 500 kb duplication at Yp11.2-Yp11.2 (chrY:6610001_ 7110000) and a 250 kb duplication at Yp11.2-Yp11.2 (chrY:7110001_7360000). CONCLUSION: In conclusion, the comprehensive application of different methods could achieve a higher detection rate and accuracy for the prenatal diagnosis of chromosomal disorders through chromosomal testing.

VvWRKY5 enhances white rot resistance in grape by promoting the jasmonic acid pathway.

Grape white rot is a disease caused by Coniella diplodiella (Speg.) Sacc. (Cd) can drastically reduce the production and quality of grape (Vitis vinifera). WRKY transcription factors play a vital role in the regulation of plant resistance to pathogens, but their functions in grape white rot need to be further explored. Here, we found that the expression of the WRKY IIe subfamily member VvWRKY5 was highly induced by Cd infection and jasmonic acid (JA) treatment. Transient injection and stable overexpression (in grape calli and Arabidopsis) demonstrated that VvWRKY5 positively regulated grape resistance to white rot. We also determined that VvWRKY5 regulated the JA response by directly binding to the promoters of VvJAZ2 (a JA signaling suppressor) and VvMYC2 (a JA signaling activator), thereby inhibiting and activating the transcription of VvJAZ2 and VvMYC2, respectively. Furthermore, the interaction between VvJAZ2 and VvWRKY5 enhanced the suppression and promotion of VvJAZ2 and VvMYC2 activities by VvWRKY5, respectively. When VvWRKY5 was overexpressed in grape, JA content was also increased. Overall, our results suggested that VvWRKY5 played a key role in regulating JA biosynthesis and signal transduction as well as enhancing white rot resistance in grape. Our results also provide theoretical guidance for the development of elite grape cultivars with enhanced pathogen resistance.

Adherence to pancreatic enzyme replacement therapy among patients with chronic pancreatitis in East China: a mixed methods study.

Pancreatic enzyme replacement therapy (PERT) has been recommended as the preferred method for pancreatic exocrine insufficiency caused by chronic pancreatitis (CP). However, at present, the patient-related factors for the poor PERT management are not clear, and there are no studies on the adherence to PERT in patients with CP in East China. This was a mixed-method study following the principle of sequential explanatory design and included two parts: a quantitative and qualitative study. A cross-sectional survey of medication adherence (MA) was first carried out, followed by a semi-structured interview to further explore and explain the influencing factors of adherence to PERT. Of the 148 patients included in this study, 48.0% had poor MA and only 12.8% had good MA. Multivariate logistic regression showed that lower levels of education and income were contributing factors for non-adherence to PERT. Semi-structured interviews with 24 patients revealed that the reasons for non-adherence also included lack of knowledge, self-adjustment of PERT, lifetime of medication, side effects of PERT, forgetfulness, financial burdens, and accessibility issues. The adherence to PERT was poor among patients with CP in East China. Healthcare providers should personalize medication strategies to improve patients' MA.

Lipid-hybrid cell-derived biomimetic functional materials: A state-of-the-art multifunctional weapon against tumors.

Tumors are among the leading causes of death worldwide. Cell-derived biomimetic functional materials have shown great promise in the treatment of tumors. These materials are derived from cell membranes, extracellular vesicles and bacterial outer membrane vesicles and may evade immune recognition, improve drug targeting and activate antitumor immunity. However, their use is limited owing to their low drug-loading capacity and complex preparation methods. Liposomes are artificial bionic membranes that have high drug-loading capacity and can be prepared and modified easily. Although they can overcome the disadvantages of cell-derived biomimetic functional materials, they lack natural active targeting ability. Lipids can be hybridized with cell membranes, extracellular vesicles or bacterial outer membrane vesicles to form lipid-hybrid cell-derived biomimetic functional materials. These materials negate the disadvantages of both liposomes and cell-derived components and represent a promising delivery platform in the treatment of tumors. This review focuses on the design strategies, applications and mechanisms of action of lipid-hybrid cell-derived biomimetic functional materials and summarizes the prospects of their further development and the challenges associated with it.

Peficitinib ameliorates 5-fluorouracil-induced intestinal damage by inhibiting aging, inflammatory factors and oxidative stress.

5-Fluorouracil (5-FU) is a conventional and effective drug for colorectal cancer patients, and it is an important part of combined chemotherapy and adjuvant chemotherapy. Chemotherapy intestinal mucositis (CIM) is a severe side effect caused by 5-FU that, induces cancer treatment failure and affects patients' quality of life. The mechanism of 5-FU-induced CIM is related to normal cell senescence induced by 5-FU. Peficitinib, a Janus Kinase (JAK) inhibitor, treats inflammatory disorders, including rheumatoid arthritis, psoriasis, and inflammatory bowel disease. However, the therapeutic role and underlying mechanism of peficitinib in CIM remain unclear. The main objective of our research was to investigate the effects of peficitinib on 5-FU-induced senescence and intestinal damage in human umbilical vein endothelial (HUVEC) cells, human intestinal epithelial (HIEC) cells and BABL/C mice. The results showed that 5-FU caused intestinal damage by inducing aging and increasing inflammation and oxidative stress. Peficitinib alleviated aging by reducing senescence-beta-galactosidase (SA-ß-gal) activity and the protein levels of aging indicators (p53, p21, p16). Moreover, peficitinib reversed the changes in senescence-associated secretory phenotype (SASP) expression caused by 5-FU. Besides, 5-FU induced release of inflammatory factors and oxidative stress indicators was reversed by peficitinib. Additionally, the combination of peficitinib and 5-FU reinforced the anticancer curative intent of 5-FU in two colorectal cancer cell lines (HCT116 cells and SW620 cells). In conclusion, peficitinib alleviates mucositis by alleviating aging, reducing inflammatory accumulation and oxidative stress and enhancing the antitumor activity of 5-FU.

Base-tuned selective 1,2-dichloromethylhydroxylation and 1,2-peroxyhydroxylation of 1,3-dienes via a tandem radical process.

A catalyst-free 1,2-difunctionalization of 1,3-dienes with CHCl3 and TBHP in the presence of NEt3 to give the dichloromethylhydroxylation products was developed. Various substituents on the aryl ring of the dienes tolerated the reactions and gave the corresponding products in moderate to good yields. When Na2CO3 was employed as the base, the key intermediate α-amino radical could not be formed; therefore, 1,2-peroxyhydroxylation products were obtained instead. This protocol provides an effective and functional group tolerant strategy for diene 1,2-difunctionalization, thus providing great potential for further functionalization and modification of synthetic molecules.

[Analysis and evaluation of bioactive constituents from different parts of Epimedium brevicornum].

A comprehensive analytical method based on ultra-fast liquid chromatography coupled with triple quadrupole/linear ion trap tandem mass spectrometry(UFLC-QTRAP-MS/MS) was established for simultaneous determination of the content of 45 bioactive constituents including flavonoids, alkaloids, amino acids, phenolic acids, and nucleosides in Epimedium brevicornum. The multiple bioactive constituents in leaves, petioles, stems and rhizomes of E. brevicornum were analyzed. The gradient elution was performed at 30 ℃ in an XBridge~® C_(18) column(4.6 mm×100 mm, 3.5 µm) with 0.4% formic acid aqueous solution-acetonitrile as the mobile phase at a flow rate of 0.8 mL·min~(-1). Single factor experiment and response surface methodology were employed to optimize the extraction conditions. Multivariate statistical analyses including systematic cluster analysis(SCA), principal component analysis(PCA), partial least squares discriminant analysis(PLS-DA), and one-way analysis of variance(One-way ANOVA) were carried out to classify the samples from different parts and identify different constituents. Grey relation analysis(GRA) and entropy weight-TOPSIS analysis were performed to build a multi-index comprehensive evaluation model for different parts of E. brevicornum. The results showed that there was a good relationship between the mass concentrations of 45 constituents and the corresponding peak areas, with the correlation coefficients(r) not less than 0.999 0. The precision, repeatability, and stability of the established method were good for all the target constituents in this study, with the relative standard deviations(RSDs) less than 5.0%(0.62%-4.9%) and the average recovery of 94.51%-105.7%. The above results indicated that the bioactive constituents varied in different parts of E. brevicornum, and the overall quality followed the trend of leaves > petioles > rhizomes > stems. This study verified the rationality of the Chinese Pharmacopoeia(2020 edition) stipulating that the medicinal part of E. brevicornum is the leaf. Moreover, our study indicated that the rhizome had the potential for medicinal development. The established method was accurate and reliable, which can be used to comprehensive evaluate and control the quality of E. brevicornum. This study provides data reference for clarifying the medicinal parts and rationally utilizing the resources of E. brevicornum.