Evaluation of Saxifraga stolonifera phenolic extracts as a potential antivenom against Deinagkistrodon acutus venom: In vitro and in vivo studies.

ETHNOPHARMACOLOGICAL RELEVANCE: In the snake-infested mountainous regions of China, Saxifraga stolonifera [L.] Meeb is widely utilized as an immediate remedy for venomous snake bites. However, the scientific understanding of S. stolonifera's efficacy in snakebite treatment remains limited and requires further investigation. AIM OF THE STUDY: The aim of this study was to assess the inhibitory effects of Saxifraga stolonifera phenolic extracts (SSPE) on Deinagkistrodon acutus venom (DAV) and explore the potential of S. stolonifera as a valuable candidate for antivenom development. MATERIALS AND METHODS: We employed our previously optimized extraction conditions to obtain SSPE. In vitro experiments utilizing diverse models were conducted to assess the inhibitory effects of the extracted phenolic compounds on DAV, specifically targeting phospholipase A2 (PLA2), proteolytic, fibrinolytic, and hyaluronidase enzymes. Furthermore, in vivo investigations were conducted to evaluate the inhibitory potential of the extracted compounds against DAV-induced hemorrhagic and edematogenic activity. To elucidate the chemical composition of the phenolic extracts, Ultra Performance Liquid Chromatography-mass spectrometry (UPLC-MS) analysis was performed. RESULTS: Our in vitro inhibition study showed that S. stolonifera was able to inhibit the activities of PLA2 enzyme, proteolytic enzyme, hyaluronidase and fibrinogenolytic. The median effective dose (ED50) values of SSPE for inhibiting PLA2 enzyme, proteolytic enzyme and hyaluronidase activities were 0.115 mg/mL, 0.026 mg/mL and 0.238 mg/mL, respectively. The DAV-induced hemorrhagic and edematogenic effects of the SSPE were also successfully inhibited in vivo, and the high SSPE concentration was able to completely inhibit the hemorrhage and edema. It is noteworthy that the mice suffered no harm from the high SSPE concentration. The composition analysis showed that the phenolic substances contained in SSPE are gallic acid, protocatechuic acid, chlorogenic acid, rutin, kaempferol-3-O-ɑ-L-rhamnoside, kaempferol-3-O-ß-D-glucopyranoside, quercetin and kaempferol. CONCLUSIONS: This study provides scientific validation of the inhibitory efficacy of S. stolonifera as an emergency treatment for venomous snake bites, offering a theoretical foundation for future drug development strategies targeting snakebite.

Block-based teaching method based on cybernetics: a trial with 115 Chinese undergraduate medical students.

BACKGROUND: Class attendance is important for academic performance. Personal interactions between teachers and students are difficult in large classes; the number of medical undergraduate students in China ranges from dozens to over 100. It is important for teachers to control the teaching process to improve student attendance and participation. METHODS: Two classes of fourth-year undergraduate medical students, with each class comprising 115 students, participated in the study. One class, the trial group, was taught by the block-based teaching method based on cybernetics. This study was conducted with three of the courses in the Introduction to Oncology subject, and the trial group's courses included several blocks. Each block had a test paper that the students responded to immediately in class using the Internet. The teacher obtained feedback from the students when the rate of correct responses to block-test questions was less than 90%. The teacher adjusted the teaching in the following blocks according to the feedback information. The other class, the control group, was taught using the traditional lecture-based teaching method. RESULTS: The average attendance in the trial group was 104/115 (90.43%), and that in the control group was 83/115 (72.17%) (p = 0.0003). The teacher adjusted the teaching three times in the radiotherapy course owing to the complex ideas. After feedback, information on chemotherapy for the upper body was adjusted once, as was that on chemotherapy for the lower body, owing to students' attitudes. The average total score of the trial group was 86.06 ± 17.46 and that of the control group was 80.38 ± 6.97 (p = 0.041). Questionnaire I showed that the trial group students' attendance and participation were better than in the control group. Questionnaire II showed that the block-based teaching method based on cybernetics was approved by the students. CONCLUSIONS: The block-based teaching method based on cybernetics used in medical classes with large numbers of Chinese undergraduate students had positive effects.

Salient Object Detection in Optical Remote Sensing Images Driven by Transformer.

Existing methods for Salient Object Detection in Optical Remote Sensing Images (ORSI-SOD) mainly adopt Convolutional Neural Networks (CNNs) as the backbone, such as VGG and ResNet. Since CNNs can only extract features within certain receptive fields, most ORSI-SOD methods generally follow the local-to-contextual paradigm. In this paper, we propose a novel Global Extraction Local Exploration Network (GeleNet) for ORSI-SOD following the global-to-local paradigm. Specifically, GeleNet first adopts a transformer backbone to generate four-level feature embeddings with global long-range dependencies. Then, GeleNet employs a Direction-aware Shuffle Weighted Spatial Attention Module (D-SWSAM) and its simplified version (SWSAM) to enhance local interactions, and a Knowledge Transfer Module (KTM) to further enhance cross-level contextual interactions. D-SWSAM comprehensively perceives the orientation information in the lowest-level features through directional convolutions to adapt to various orientations of salient objects in ORSIs, and effectively enhances the details of salient objects with an improved attention mechanism. SWSAM discards the direction-aware part of D-SWSAM to focus on localizing salient objects in the highest-level features. KTM models the contextual correlation knowledge of two middle-level features of different scales based on the self-attention mechanism, and transfers the knowledge to the raw features to generate more discriminative features. Finally, a saliency predictor is used to generate the saliency map based on the outputs of the above three modules. Extensive experiments on three public datasets demonstrate that the proposed GeleNet outperforms relevant state-of-the-art methods. The code and results of our method are available at https://github.com/MathLee/GeleNet.

Could long-term dialysis vintage and abnormal calcium, phosphorus and iPTH control accelerate aging among the maintenance hemodialysis population?

OBJECTIVE: Aging is a complex process of physiological dysregulation of the body system and is common in hemodialysis patients. However, limited studies have investigated the links between dialysis vintage, calcium, phosphorus, and iPTH control and aging. The purpose of the current study was to examine these associations. METHODS: During 2020, a cross-sectional study was conducted in 3025 hemodialysis patients from 27 centers in Anhui Province, China. Biological age was calculated by a formula using chronological age and clinical indicators. The absence of the target range for serum phosphorus (0.87-1.45 mmol/L), corrected calcium (2.1-2.5 mmol/L) and iPTH (130-585 pg/mL) were identified as abnormal calcium, phosphorus, and iPTH control. RESULTS: A total of 1131 hemodialysis patients were included, 59.2% of whom were males (669/1131). The mean (standard deviation) of actual age and biological age were 56.07 (12.79) years and 66.94 (25.88), respectively. The median of dialysis vintage was 4.3 years. After adjusting for the confounders, linear regression models showed patients with abnormal calcium, phosphorus, and iPTH control and on hemodialysis for less than 4.3 years (B = 0.211, p = .002) or on hemodialysis for 4.3 years or more (B = 0.302, p < .001), patients with normal calcium, phosphorus, and iPTH control and on hemodialysis for 4.3 years or more (B = 0.087, p = .013) had a higher biological age. CONCLUSION: Our findings support the hypothesis that long-term hemodialysis and abnormal calcium, phosphorus, and iPTH control may accelerate aging in the hemodialysis population. Further studies are warrant to verify the significance of maintaining normal calcium-phosphorus metabolism in aging.

Thiol-based modification of MarR protein VnrR regulates resistance towards nitrofuran in Vibrio cholerae by promoting the expression of a novel nitroreductase VnrA and of NO-detoxifying enzyme HmpA.

AIMS: Epidemiological investigations have indicated low resistance towards nitrofuran in clinical isolates, suggesting its potential application in the treatment of multidrug-resistant bacteria. Therefore, it is valuable to explore the mechanism of bacterial resistance to nitrofuran. RESULTS: Through phenotypic screening of ten multiple antibiotic resistance regulator (MarR) proteins in Vibrio cholerae, we discovered that the regulator VnrR (VCA1058) plays a crucial role in defending against nitrofuran, specifically furazolidone (FZ). Our findings demonstrate that VnrR responds to FZ metabolites, such as hydroxylamine, methylglyoxal, H2O2, ß-hydroxyetiylhydrazine. Notably, VnrR exhibits reversible responses to the addition of H2O2 through three cysteine residues (Cys180, Cys223, Cys247), leading to the derepression of its upstream gene, vnrA (vca1057). Gene vnrA encodes a novel nitroreductase, which directly contributes to the degradation of FZ. Our study reveals that V. cholerae metabolizes FZ via the vnrR-vnrA system and achieves resistance to FZ with the assistance of the classical reactive oxygen/nitrogen species scavenging pathway. INNOVATION AND CONCLUSION: This study represents a significant advancement in understanding the antibiotic resistance mechanisms of V. cholerae and other pathogens. Our findings demonstrate that the MarR family regulator, VnrR, responds to the FZ metabolite H2O2, facilitating the degradation and detoxification of this antibiotic in a thiol-dependent manner. These insights not only enrich our knowledge of antibiotic resistance but also provide new perspectives for the control and prevention of multidrug-resistant bacteria.

ActivePPI: quantifying protein-protein interaction network activity with Markov random fields.

MOTIVATION: Protein-protein interactions (PPI) are crucial components of the biomolecular networks that enable cells to function. Biological experiments have identified a large number of PPI, and these interactions are stored in knowledge bases. However, these interactions are often restricted to specific cellular environments and conditions. Network activity can be characterized as the extent of agreement between a PPI network (PPIN) and a distinct cellular environment measured by protein mass spectrometry, and it can also be quantified as a statistical significance score. Without knowing the activity of these PPI in the cellular environments or specific phenotypes, it is impossible to reveal how these PPI perform and affect cellular functioning. RESULTS: To calculate the activity of PPIN in different cellular conditions, we proposed a PPIN activity evaluation framework named ActivePPI to measure the consistency between network architecture and protein measurement data. ActivePPI estimates the probability density of protein mass spectrometry abundance and models PPIN using a Markov-random-field-based method. Furthermore, empirical P-value is derived based on a nonparametric permutation test to quantify the likelihood significance of the match between PPIN structure and protein abundance data. Extensive numerical experiments demonstrate the superior performance of ActivePPI and result in network activity evaluation, pathway activity assessment, and optimal network architecture tuning tasks. To summarize it succinctly, ActivePPI is a versatile tool for evaluating PPI network that can uncover the functional significance of protein interactions in crucial cellular biological processes and offer further insights into physiological phenomena. AVAILABILITY AND IMPLEMENTATION: All source code and data are freely available at https://github.com/zpliulab/ActivePPI.

Phosphoproteomics reveals content and signaling differences between neonatal and adult platelets.

Background and Objective: Recent clinical studies have shown that transfusions of adult platelets increase morbidity and mortality in preterm infants. Neonatal platelets are hyporesponsive to agonist stimulation, and emerging evidence suggests developmental differences in platelet immune functions. This study was designed to compare the proteome and phosphoproteome of resting adult and neonatal platelets. Methods: We isolated resting umbilical cord blood-derived platelets from healthy full term neonates (n=9) and resting blood platelets from healthy adults (n=7), and compared protein and phosphoprotein contents using data independent acquisition mass spectrometry. Results: We identified 4745 platelet proteins with high confidence across all samples. Adult and neonatal platelets clustered separately by principal component analysis. Adult platelets were significantly enriched for immunomodulatory proteins, including ß2 microglobulin and CXCL12, whereas neonatal platelets were enriched for ribosomal components and proteins involved in metabolic activities. Adult platelets were enriched for phosphorylated GTPase regulatory enzymes and proteins participating in trafficking, which may help prime them for activation and degranulation. Neonatal platelets were enriched for phosphorylated proteins involved in insulin growth factor signaling. Conclusions: Using state-of-the-art mass spectrometry, our findings expanded the known neonatal platelet proteome and identified important differences in protein content and phosphorylation compared with adult platelets. These developmental differences suggested enhanced immune functions for adult platelets and presence of a molecular machinery related to platelet activation. These findings are important to understanding mechanisms underlying key platelet functions as well as the harmful effects of adult platelet transfusions given to preterm infants.

Causal relationships between CD25 on immune cells and hip osteoarthritis.

Objectives: Previous research has indicated a potential association between immune factors and osteoarthritis (OA), but the causal relationship between CD25 expression on immune cells and hip OA remains enigmatic. To shed light on this relationship, this study utilized the two-sample Mendelian Randomization (MR) method. Methods: Leveraging genome-wide association studies (GWAS) data from the UK Biobank and arcOGEN, the investigation encompasses a substantial European cohort comprising 15,704 hip OA cases and 378,169 controls. Genetic insights into CD25 stem from a subgroup of 3,757 individuals with European ancestry, encompassing 77 CD25-related traits. Several MR methods were applied, and robustness was assessed through heterogeneity and sensitivity analysis. Results: Among the 77 traits examined, 66 shared the same single nucleotide polymorphisms (SNPs) with hip OA. Of these, 7 CD25-related traits were found to be causally associated with hip OA (adjusted P><0.05), with F-statistics ranging from 33 to 122. These traits are specifically related to CD4+CD25+ T cells, exhibiting odds ratios (OR) and 95% confidence intervals (CI) less than 1. Notably, no causal link was discerned with the CD8+CD25+ T cell subset. Within absolute count (AC) and relative count (RC) trait types, a significant causal relationship was observed solely between CD4+CD25+ T cells and hip OA, without subtype localization. A more intricate examination of CD25 expression levels within the CD4+CD25+ T cell subset revealed a correlation with the CD39+ regulatory T (Treg) subset and hip OA, particularly within the CD39+ activated Treg subset. Furthermore, a notable causal relationship emerged between CD25 expression levels in the CD45RA- not Treg subset and hip OA. However, no significant causal link was established with any subsets of B cells. Conclusion: The genetic prediction suggests that CD25, particularly within the realm of CD4+CD25+ T cells, may exert a protective influence against the development of hip OA. These findings provide a novel therapeutic approach for the prevention and treatment of hip OA.

An optimal Fe-C coordination ensemble for hydrocarbon chain growth: a full Fischer-Tropsch synthesis mechanism from machine learning.

Fischer-Tropsch synthesis (FTS, CO + H2 → long-chain hydrocarbons) because of its great significance in industry has attracted huge attention since its discovery. For Fe-based catalysts, after decades of efforts, even the product distribution remains poorly understood due to the lack of information on the active site and the chain growth mechanism. Herein powered by a newly developed machine-learning-based transition state (ML-TS) exploration method to treat properly reaction-induced surface reconstruction, we are able to resolve where and how long-chain hydrocarbons grow on complex in situ-formed Fe-carbide (FeCx) surfaces from thousands of pathway candidates. Microkinetics simulations based on first-principles kinetics data further determine the rate-determining and the selectivity-controlling steps, and reveal the fine details of the product distribution in obeying and deviating from the Anderson-Schulz-Flory law. By showing that all FeCx phases can grow coherently upon each other, we demonstrate that the FTS active site, namely the A-P5 site present on reconstructed Fe3C(031), Fe5C2(510), Fe5C2(021), and Fe7C3(071) terrace surfaces, is not necessarily connected to any particular FeCx phase, rationalizing long-standing structure-activity puzzles. The optimal Fe-C coordination ensemble of the A-P5 site exhibits both Fe-carbide (Fe4C square) and metal Fe (Fe3 trimer) features.

Introducing the grafted poly(acrylic acid-co-butyl acrylate) branches onto biological corn starch macromolecule for imparting it with superior sizing properties.

The objective of this study was to survey the influence of poly(acrylic acid-co-butyl acrylate) [P(AA-co-BA)] branches on the sizing properties (i.e., paste stability, adhesion, properties of film and sized warps) of biological macromolecule (corn starch) for further promoting the properties of bromoisobutyryl esterified starch (BBES) and developing a new biobased sizing agent [BBES-g-P(AA-co-BA)]. The sizing properties of BBES-g-P(AA-co-BA) were estimated in comparison with acid-hydrolyzed starch (AHS) and BBES. Compared with the two starches, BBES-g-P(AA-co-BA) displayed higher paste stability, bonding forces to both polyester and polyester/cotton roving, film elongation and water solubility, as well as lower film strength. And the increased grafting ratio exhibited positive effects on these properties of BBES-g-P(AA-co-BA). The properties containing increase in strength, loss in extension, abrasion resistance and hairiness of polyester and polyester/cotton blended yarns sized with BBES-g-P(AA-co-BA), were superior to those sized with AHS and BBES, respectively, indicating that the incorporation of P(AA-co-BA) branches onto BBES could further promote the sizing qualities of both yarns. The BBES-g-P(AA-co-BA) with a grafting ratio of 16.51 % was concluded to size both yarns for improvement of yarn quality.

The efficacy and safety of opioid-free anesthesia combined with ultrasound-guided intermediate cervical plexus block vs. opioid-based anesthesia in thyroid surgery-a randomized controlled trial.

PURPOSE: In the context of the current comfort medicine and enhanced recovery after surgery, there is a demand for a new anesthesia method to reduce adverse reactions and accelerate recovery after surgery. This randomized controlled trial aimed to compare the efficacy and safety between opioid-free anesthesia (OFA) combined with ultrasound-guided intermediate cervical plexus block (ICPB) and opioid-based anesthesia in patients after thyroid surgery. METHODS: In this study, 75 patients scheduled for thyroid surgery under general anesthesia were randomly allocated into two groups. The primary outcome included the incidence of nausea within 24 h after surgery. The main secondary outcomes included the incidence of vomiting and the visual analog score (VAS) scores within 24 h after surgery as well as the quality of recovery 40 questionnaires (QoR-40) scores 24 h after surgery. RESULTS: In the OFA group, the incidence of postoperative nausea was 6.1%, compared to 39.4% in the control group (p = 0.001). No patient presented with postoperative vomiting in the OFA group, while 15.2% of patients suffered from postoperative vomiting in the control group (p = 0.063). The VAS scores of patients in the postanesthetic care unit (PACU) and 2 h, 4 h, and 6 h after surgery were lower in the OFA group, and the difference is statistically significant. Besides, the VAS scores of patients at rest (p = 1.000) and during swallowing (p = 1.000) 24 h after surgery were comparable. CONCLUSION: Compared with opioid-based anesthesia, the OFA combined with the ultrasound-guided ICPB can better improve patients' postoperative recovery, reduce nausea, and decrease pain scores. TRIAL REGISTRATION: Chinese Clinical Trial Regisrty, ChiCTR2200056344, https://www.chictr.org.cn.

Effect of laparoscopic complete mesocolic excision combined with immunotherapy and its impact on immune function and tumor markers in elderly patients with colon cancer.

Objective: To determine the effect of laparoscopic complete mesocolic excision combined with immunotherapy and its impact on immune function and tumor markers in elderly patients with colon cancer. Methods: This is a clinical comparative study. Eighty elderly patients with colon cancer hospitalized in the No.2 Hospital of Baoding from May 2020 to May 2022 were randomly divided into two groups, with 40 cases in each group. Patients in the study group received laparoscopic complete mesocolic resection combined with ubenimex orally. While patients in the control group received routine open surgery. The surgical indexes, surgical complications, and the changes of immune molecules and tumor markers before and after treatment were compared between the two groups. Results: The amount of intraoperative bleeding, retention time of drainage tube and postoperative length of stay in the hospital in the study group were significantly better than those in the control group (p=0.000). The incision length of the study group was significantly shorter than that of the control group, the number of lymph nodes removed during the operation was significantly higher than that of the control group, and the incidence of surgical complications was significantly lower than that of the control group (p<0.05). After treatment, the levels of immune molecules in the study group were remarkably higher than those in the control group (p<0.05), while the levels of tumor markers were much lower than those in the latter group (p=0.000). Conclusion: Laparoscopic complete mesocolic excision combined with immunotherapy exhibits a superior therapeutic effect to traditional open surgery in elderly patients with colon cancer, and is worthy of clinical promotion.

Right heart thrombus in acute pulmonary embolism: A single center experience in China.

Right heart thrombus (RHT) is a rare but life-threatening condition in acute pulmonary embolism (APE) without clear management guidelines. This study aimed to address the clinical characteristics and outcomes of RHT-APE in Chinese patients. In this study, 17 RHT-APE and 329 non-RHT-APE patients, who were diagnosed between September 2015 and August 2019, were retrospectively recruited with the median follow-up was 360 days. The overall prevalence of RHT was 4.91% in APE. Its prevalence increased along the increase of APE risk stratifications. Comparisons showed that with higher proportion of male gender and younger age, RHT-APE patients also had worse hemodynamic instability and heart function, and higher risk stratification levels than non-RHT-APE patients. After adjusting by age and gender, multivariate logistic regression analysis found high/intermediate-high risk stratification, decreased right ventricular (RV) motion, NT-proBNP >600 pg/mL, and RV dysfunction were risk factors for RHT. Kaplan-Meier analysis showed non-RHT had better prognosis than RHT patients (30-day survival: log-rank: p < 0.001; 90-day survival: log-rank: p = 0.002). The multivariate logistic regression analysis showed RHT was an independent risk factor for 30-day mortality in APE. The subgroup analysis showed RHT would result in worse outcomes in patients who already had higher APE early mortality risk. RHT would increase the risk of 30- and 90-day mortality in APE. More attention should be paid to young male APE patients with decreased RV motion, NT-proBNP >600 pg/mL, RV dysfunction, or high level of risk stratification, to exclude the coexistence of RHT.

Locking water molecules via ternary O-H⋯O intramolecular hydrogen bonds in perhydroxylated closo-dodecaborate.

A multitude of applications related to perhydroxylated closo-dodecaborate B12(OH)122- in the condensed phase are inseparable from the fundamental mechanisms underlying the high water orientation selectivity based on the base B12(OH)122-. Herein, we directly compare the structural evolution of water clusters, ranging from monomer to hexamer, oriented by functional groups in the bases B12H122-, B12H11OH2- and B12(OH)122- using multiple theoretical methods. A significant revelation is made regarding B12(OH)122-: each additional water molecule is locked into the intramolecular hydrogen bond B-O-H ternary ring in an embedded form. This new pattern of water cluster growth suggests that B-(H-O)⋯H-O interactions prevail over the competition from water-hydrogen bonds (O⋯H-O), distinguishing it from the behavior observed in B12H122- and B12H11OH2- bases, in which competition arises from a mixed competing model involving dihydrogen bonds (B-H⋯H-O), conventional hydrogen bonds (B-(H-O)⋯H-O) and water hydrogen bonds (O⋯H-O). Through aqueous solvation and ab initio molecular dynamics analysis, we further demonstrate the largest water clusters in the first hydrated shell with exceptional thermodynamic stability around B12(OH)122-. These findings provide a solid scientific foundation for the design of boron cluster chemistry incorporating hydroxyl-group-modified borate salts with potential implications for various applications.

Simulating Chern insulators on a superconducting quantum processor.

The quantum Hall effect, fundamental in modern condensed matter physics, continuously inspires new theories and predicts emergent phases of matter. Here we experimentally demonstrate three types of Chern insulators with synthetic dimensions on a programable 30-qubit-ladder superconducting processor. We directly measure the band structures of the 2D Chern insulator along synthetic dimensions with various configurations of Aubry-André-Harper chains and observe dynamical localisation of edge excitations. With these two signatures of topology, our experiments implement the bulk-edge correspondence in the synthetic 2D Chern insulator. Moreover, we simulate two different bilayer Chern insulators on the ladder-type superconducting processor. With the same and opposite periodically modulated on-site potentials for two coupled chains, we simulate topologically nontrivial edge states with zero Hall conductivity and a Chern insulator with higher Chern numbers, respectively. Our work shows the potential of using superconducting qubits for investigating different intriguing topological phases of quantum matter.

Pulsed thermoreflectance imaging for thermophysical properties measurement of GaN epitaxial heterostructures.

Multilayer heterostructures composed of a substrate and an epitaxial film are widely utilized in advanced electronic devices. However, thermal bottlenecks constrain their performance and reliability, and efficient approaches to comprehensively measure the thermophysical properties of heterostructures are urgently needed. In this work, a pulsed thermoreflectance imaging (PTI) method is proposed, which combines the transient temperature mapping of thermoreflectance thermal imaging with transient pulsed excitation. By executing merely three transient tests, six thermophysical properties, including the film thermal conductivity and specific heat capacity, the substrate thermal conductivity and specific heat capacity, the film-substrate thermal boundary resistance, and the equivalent thermal conductivity of the insulating layer, can be simultaneously measured in a heterostructure sample. The proposed method applies a pulsed current excitation to a metal heater line on the sample surface and utilizes the thermoreflectance thermal imaging system to measure the temperature of different spatial regions on the sample surface at different time windows. The temporal and spatial variation information of the temperature field is then extracted and combined with finite element method inversion calculation to obtain the thermophysical properties of heterostructures. To validate the accuracy and reliability of this method, we conducted measurements on a GaN-on-SiC heterostructure sample and obtained thermophysical properties consistent with the representative literature data that have previously been reported. The proposed PTI method, characterized by its high sensitivity, demonstrates good efficiency and reliability in conducting comprehensive thermophysical property characterization of GaN epitaxial heterostructures.

E3 ubiquitin ligases SINA4 and SINA11 regulate anthocyanin biosynthesis by targeting the IAA29-ARF5-1-ERF3 module in apple.

Auxin/indole-3-acetic acid (AUX/IAA) and auxin response factor (ARF) proteins are important components of the auxin signalling pathway, but their ubiquitination modification and the mechanism of auxin-mediated anthocyanin biosynthesis remain elusive. Here, the ARF MdARF5-1 was identified as a negative regulator of anthocyanin biosynthesis in apple, and it integrates auxin and ethylene signals by inhibiting the expression of the ethylene response factor MdERF3. The auxin repressor MdIAA29 decreased the inhibitory effect of MdARF5-1 on anthocyanin biosynthesis by attenuating the transcriptional inhibition of MdERF3 by MdARF5-1. In addition, the E3 ubiquitin ligases MdSINA4 and MdSINA11 played negative and positive regulatory roles in anthocyanin biosynthesis by targeting MdIAA29 and MdARF5-1 for ubiquitination degradation, respectively. MdSINA4 destabilized MdSINA11 to regulate anthocyanin accumulation in response to auxin signalling. In sum, our data revealed the crosstalk between auxin and ethylene signals mediated by the IAA29-ARF5-1-ERF3 module and provide new insights into the ubiquitination modification of the auxin signalling pathway.

Development and application of hepatocellular carcinoma risk prediction model based on clinical characteristics and liver related indexes.

BACKGROUND: Hepatocellular carcinoma (HCC) is difficult to diagnose with poor therapeutic effect, high recurrence rate and has a low survival rate. The survival of patients with HCC is closely related to the stage of diagnosis. At present, no specific serological indicator or method to predict HCC, early diagnosis of HCC remains a challenge, especially in China, where the situation is more severe. AIM: To identify risk factors associated with HCC and establish a risk prediction model based on clinical characteristics and liver-related indicators. METHODS: The clinical data of patients in the Affiliated Hospital of North Sichuan Medical College from 2016 to 2020 were collected, using a retrospective study method. The results of needle biopsy or surgical pathology were used as the grouping criteria for the experimental group and the control group in this study. Based on the time of admission, the cases were divided into training cohort (n = 1739) and validation cohort (n = 467). Using HCC as a dependent variable, the research indicators were incorporated into logistic univariate and multivariate analysis. An HCC risk prediction model, which was called NSMC-HCC model, was then established in training cohort and verified in validation cohort. RESULTS: Logistic univariate analysis showed that, gender, age, alpha-fetoprotein, and protein induced by vitamin K absence or antagonist-II, gamma-glutamyl transferase, aspartate aminotransferase and hepatitis B surface antigen were risk factors for HCC, alanine aminotransferase, total bilirubin and total bile acid were protective factors for HCC. When the cut-off value of the NSMC-HCC model joint prediction was 0.22, the area under receiver operating characteristic curve (AUC) of NSMC-HCC model in HCC diagnosis was 0.960, with sensitivity 94.40% and specificity 95.35% in training cohort, and AUC was 0.966, with sensitivity 90.00% and specificity 94.20% in validation cohort. In early-stage HCC diagnosis, the AUC of NSMC-HCC model was 0.946, with sensitivity 85.93% and specificity 93.62% in training cohort, and AUC was 0.947, with sensitivity 89.10% and specificity 98.49% in validation cohort. CONCLUSION: The newly NSMC-HCC model was an effective risk prediction model in HCC and early-stage HCC diagnosis.