Predictive value of blood coagulation and routine blood indices for rebleeding after endoscopic treatment in hepatitis B-related cirrhotic patients with esophagogastric fundal varices: a logistic regression model analysis.

OBJECTIVE: To evaluate the predictive value of blood coagulation and routine blood indices for rebleeding after endoscopic treatment of ruptured esophagogastric fundal varices (EGVB) in cirrhotic patients with hepatitis B infection. METHODS: This retrospective analysis included 248 patients with hepatitis B-related cirrhosis and EGVB who received initial endoscopic treatment from October 2019 to March 2022 and were followed up for 12 months. Patients were divided into rebleeding and non-rebleeding groups. Laboratory indices were analyzed, and univariate and multivariate analyses identified predictors of rebleeding. The efficacy of a logistic regression model was evaluated using Receiver Operating Characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA), and a risk factor nomogram was constructed for assessing the predictive efficiency of those risk factors. RESULTS: Univariate analysis showed significant differences in portal vein diameters and lower Child-Pugh scores in the rebleeding group in contrast to those in the non-rebleeding group. Key laboratory markers such as platelet count (PLT), albumin (ALB), alanine aminotransferase (ALT), lymphocytes (LYM), and prognostic nutritional index (PNI) were lower, while prothrombin time (PT) and lactate levels (LN) were higher in the rebleeding group than those in the non-rebleeding group. Multivariate analysis identified portal vein diameter, PLT, ALT, PT, LYM, and PNI as significant predictors of rebleeding. The logistic model demonstrated high accuracy (AUC=0.986) and clinical value, validated by ROC curves, calibration curves (C-index =0.986), and DCA results. A risk factor predictive nomogram was successfully constructed. CONCLUSION: This study developed a logistic regression model with a nomogram for predicting EGVB-related rebleeding in patients with hepatitis B-related cirrhosis, achieving an AUC of 0.986, indicating high accuracy and significant clinical relevance.

GAB1 attenuates lipopolysaccharide­mediated endothelial dysfunction via regulation of SOCS3.

Endothelial dysfunction is a crucial pathogenetic mechanism for sepsis. GRB2-associated binder 1 (GAB1) alleviates sepsis-induced multi-organ damage; however, to the best of our knowledge, its function in endothelial dysfunction in sepsis remains unclear. HUVECs were induced by lipopolysaccharide (LPS) to simulate endothelial cell injury under sepsis. Cell transfection was conducted to achieve GAB1 overexpression or suppressor of cytokine signaling 3 (SOCS3) knockdown. The expression levels of GAB1 and SOCS3 were detected by reverse transcription-quantitative PCR and western blotting. Cell viability, apoptosis and migration were assessed using Cell Counting Kit-8, TUNEL and wound healing assays, respectively. The production of cytokines and nitric oxide (NO) was detected using commercial kits. The interaction between GAB1 and SOCS3 was confirmed using a co-immunoprecipitation assay. GAB1 was downregulated in LPS-induced HUVECs. However, GAB1 overexpression significantly mitigated LPS-induced cell viability decrease and apoptosis in HUVECs, accompanied by upregulation of Bcl2 expression, and downregulation of Bax and cleaved caspase-3 expression. GAB1 also inhibited the production of pro-inflammatory cytokines and increased NO level, increased the levels of endothelial NO synthase (eNOS) and phosphorylated (p)-eNOS, and promoted migration in LPS-induced HUVECs. However, SOCS3 knockdown partially weakened the effects of GAB1 overexpression on cell viability, apoptosis, inflammation, p-eNOS, eNOS expression and NO levels in LPS-induced HUVECs. In addition, GAB1 and SOCS3 regulated Janus kinase 2 (JAK2)/STAT3 signaling in LPS-induced HUVECs. In conclusion, GAB1 exerted a protective effect against LPS-induced endothelial cell apoptosis, inflammation and dysfunction by modulating the SOCS3/JAK2/STAT3 signaling pathway.

Modified pedicle screw-rod fixation versus open reduction plate fixation for the management of pubic symphysis diastasis: A retrospective study.

Objective: Surgical intervention and fixation is the recognized measurement to treat pubic symphysis diastasis caused by high-energy trauma. The purpose of this retrospective study was to assess the clinical application of modified pedicle screw-rod fixation (modified PSRF) and open reduction plate fixation (ORPF) for treating pubic symphysis diastasis. Methods: The data of this retrospective analysis were collected from 32 patients with pubic symphysis diastasis managed with modified PSRF or ORPF from January 2012 to December 2017, with or without posterior fixation. Indicators of clinical assessments including operating time, intraoperative blood loss, relevant surgical complications as well as follow-up were recorded. Majeed scores were performed for functional evaluation, as well as Matta criteria were applied to evaluate the quality of reduction. Results: The average time from injury to operation was 2.9 days in modified PSRF group and 3.2 days in ORPF group. Significant differences regarding average operation time (41.8 min versus 64.3 min) and average intraoperative blood loss (46.6 ml versus 304.6 ml) were presented between modified PSRF groups and ORPF group. Neither Majeed scores nor Matta evaluation showed a significant difference between two groups. In ORPF group, the incision infection occurred in one patient and two patients developed loosening of screws. In modified PSRF group, loosening of screws was found in one patient during the operative procedure and one patient experienced femoral nerve palsy. Irritation to the lateral femoral cutaneous nerve (LFCN) was detected in two patients in modified PSRF group. Conclusions: Satisfactory clinical outcomes were provided with applications of both fixation methods for treating pubic symphysis diastasis. Modified PSRF, as a minimal invasive technique, could serve as an effective and reasonable option for treating pubic symphysis diastasis.Level of evidence: III: retrospective cohort study.Trial registration: researchregistry3906.

Efficacy and safety analysis of PD-1 combined with regorafenib in the treatment of advanced hepatocellular carcinoma.

OBJECTIVE: To investigate the therapeutic efficacy and safety of programmed death-1 (PD-1) inhibitors combined with regorafenib in the treatment of advanced hepatocellular carcinoma (HCC). METHODS: A retrospective analysis was performed on 82 patients diagnosed with advanced HCC at Lanzhou Petrochemical General Hospital and the Second People's Hospital of Lanzhou City from October 2021 to October 2022. Patients were divided into two groups: the observation group (42 patients) received combined therapy with regorafenib and a PD-1 inhibitor, while the control group (40 patients) received only regorafenib monotherapy. Treatment efficacy, changes in serum tumor markers pre- and post-treatment, incidence of adverse reactions, progression-free survival (PFS), 1-year survival rate, and independent prognostic factors were evaluated for both groups. RESULTS: The treatment efficacy in the observation group was significantly better than that in the control group (P<0.05). Post-treatment levels of VEGF, sIL-2R, and CEA were significantly lower in the observation group compared to the control group (all P<0.05). The incidence of adverse reactions was similar between the two groups (P>0.05). However, the observation group demonstrated a significantly higher median PFS and 1-year survival rate than the control group (both P<0.05). Vascular invasion, degree of differentiation, and treatment regimen were identified as independent prognostic factors affecting outcomes (all P<0.05). CONCLUSION: For patients with advanced HCC, integrating PD-1 inhibitors with regorafenib treatment not only enhances clinical efficacy but also maintains safety. This combination therapy significantly improves progression-free survival and 1-year survival rates, supporting its further clinical application.

[Atorvastatin promotes the healing of alveolar bone defect in rats and its effect on Wnt/ß-catenin signaling pathway].

PURPOSE: To investigate the therapeutic effect of atorvastatin on alveolar bone defect model in rats, and to observe the effect of atorvastatin on Wnt/ß-catenin. METHODS: Thirty rats were randomly divided into normal group (group N), model group (group M) and atorvastatin administration group (group ATV). Except group N, bone defects were made in other rats' alveolar bone to construct alveolar bone defect model. After successful modeling, 20 mg/kg atorvastatin suspension was administered by gavage in group ATV, and the same amount of sodium carboxymethyl cellulose solution was administered by gavage in group N and group M for twenty-one days. After the last administration, tail vein blood was collected to detect the concentrations of serum osteoprotegerin (OPG), alkaline phosphatase (ALP) and osteocalcin (BPG). H-E staining was used to observe the pathological changes of maxillary defect area, and lane Sandhu score was performed. Tartrate resistant acid phosphatase(TRAP) staining was used to detect the number of osteoclasts in the defect area. Real time fluorescence quantitative PCR(RT-qPCR) and Western blot(WB) were used to detect Wnt, ß-catenin and Runx2 mRNA protein expression. Statistical analysis was performed with SPSS 23.0 software package. RESULTS: Compared with group N, the concentrations of OPG, ALP, BGP and Lane Sandhu score in group M decreased, and the number of osteoclasts increased. Compared with group M, the concentrations of OPG, ALP and BGP and lane Sandhu score in group ATV increased, and the number of osteoclasts decreased. After H-E staining, the amount of bone formation in maxillary defect area in group N was more,there was fewer bone tissues in the defect area in group M, the amount of bone tissues in the defect area increased in group ATV. Compared with group N, Wnt, ß-catenin and Runx2 mRNA protein decreased. Compared with group M, Wnt, ß-catenin and Runx2 mRNA protein expression increased. CONCLUSIONS: Atorvastatin can promote the healing of alveolar bone defect and accelerate bone reconstruction in rat models. This effect may be related to the activation of Wnt/ß-catenin signaling pathway.

Machine Learning in Hypertrophic Cardiomyopathy: Nonlinear Model From Clinical and CMR Features Predicting Cardiovascular Events.

BACKGROUND: The cumulative burden of hypertrophic cardiomyopathy (HCM) is significant, with a noteworthy percentage (10%-15%) of patients with HCM per year experiencing major adverse cardiovascular events (MACEs). A current risk stratification scheme for HCM had only limited accuracy in predicting sudden cardiac death (SCD) and failed to account for a broader spectrum of adverse cardiovascular events and cardiac magnetic resonance (CMR) parameters. OBJECTIVES: This study sought to develop and evaluate a machine learning (ML) framework that integrates CMR imaging and clinical characteristics to predict MACEs in patients with HCM. METHODS: A total of 758 patients with HCM (67% male; age 49 ± 14 years) who were admitted between 2010 and 2017 from 4 medical centers were included. The ML model was built on the internal discovery cohort (533 patients with HCM, admitted to Fuwai Hospital, Beijing, China) by using the light gradient-boosting machine and internally evaluated using cross-validation. The external test cohort consisted of 225 patients with HCM from 3 medical centers. A total of 14 CMR imaging features (strain and late gadolinium enhancement [LGE]) and 23 clinical variables were evaluated and used to inform the ML model. MACEs included a composite of arrhythmic events, SCD, heart failure, and atrial fibrillation-related stroke. RESULTS: MACEs occurred in 191 (25%) patients over a median follow-up period of 109.0 months (Q1-Q3: 73.0-118.8 months). Our ML model achieved areas under the curve (AUCs) of 0.830 and 0.812 (internally and externally, respectively). The model outperformed the classic HCM Risk-SCD model, with significant improvement (P < 0.001) of 22.7% in the AUC. Using the cubic spline analysis, the study showed that the extent of LGE and the impairment of global radial strain (GRS) and global circumferential strain (GCS) were nonlinearly correlated with MACEs: an elevated risk of adverse cardiovascular events was observed when these parameters reached the high enough second tertiles (11.6% for LGE, 25.8% for GRS, -17.3% for GCS). CONCLUSIONS: ML-empowered risk stratification using CMR and clinical features enabled accurate MACE prediction beyond the classic HCM Risk-SCD model. In addition, the nonlinear correlation between CMR features (LGE and left ventricular pressure gradient) and MACEs uncovered in this study provides valuable insights for the clinical assessment and management of HCM.

Exploiting hosts and vectors: viral strategies for facilitating transmission.

Viruses have developed various strategies to ensure their survival and transmission. One intriguing strategy involves manipulating the behavior of infected arthropod vectors and hosts. Through intricate interactions, viruses can modify vector behavior, aiding in crossing barriers and improving transmission to new hosts. This manipulation may include altering vector feeding preferences, thus promoting virus transmission to susceptible individuals. In addition, viruses employ diverse dissemination methods, including cell-to-cell and intercellular transmission via extracellular vesicles. These strategies allow viruses to establish themselves in favorable environments, optimize replication, and increase the likelihood of spreading to other individuals. Understanding these complex viral strategies offers valuable insights into their biology, transmission dynamics, and potential interventions for controlling infections. Unraveling interactions between viruses, hosts, and vectors enables the development of targeted approaches to effectively mitigate viral diseases and prevent transmission.

Tweety homolog 3 promotes colorectal cancer progression through mutual regulation of histone deacetylase 7.

Colorectal cancer (CRC) is one of the leading cancers worldwide, with metastasis being a major cause of high mortality rates among patients. In this study, dysregulated gene Tweety homolog 3 (TTYH3) was identified by Gene Expression Omnibus database. Public databases were used to predict potential competing endogenous RNAs (ceRNAs) for TTYH3. Quantitative real-time polymerase chain reaction, western blot, and immunohistochemistry were utilized to analyze TTYH3 and histone deacetylase 7 (HDAC7) levels. Luciferase assays confirmed miR-1271-5p directly targeting the 3' untranslated regions of TTYH3 and HDAC7. In vitro experiments such as transwell and human umbilical vein endothelial cell tube formation, as well as in vivo mouse models, were conducted to assess the biological functions of TTYH3 and HDAC7. We discovered that upregulation of TTYH3 in CRC promotes cell migration by affecting the Epithelial-mesenchymal transition pathway, which was independent of its ion channel activity. Mechanistically, TTYH3 and HDAC7 functioned as ceRNAs, reciprocally regulating each other's expression. TTYH3 competes for binding miR-1271-5p, increasing HDAC7 expression, facilitating CRC metastasis and angiogenesis. This study reveals the critical role of TTYH3 in promoting CRC metastasis through ceRNA crosstalk, offering new insights into potential therapeutic targets for clinical intervention.

Short-Term and Imminent Rainfall Prediction Model Based on ConvLSTM and SmaAT-UNet.

Short-term precipitation forecasting methods are mainly divided into statistical forecasting, numerical model-based forecasting, and radar image extrapolation techniques. The two methods based on statistical prediction and numerical model have the disadvantages of being unstable and generating large errors. Therefore, this study proposes the use of deep learning for radar image extrapolation for precipitation forecasting, in particular by developing algorithms for ConvLSTM and SmaAT-UNet. The ConvLSTM model is a fusion of a CNN (Convolutional Neural Network) and LSTM (Long Short-Term Memory network), which solves the challenge of processing spatial sequence data, which is a task that traditional LSTM models cannot accomplish. At the same time, SmaAT-UNet enhances the traditional UNet structure by incorporating the CBAM (Convolutional Block Attention Module) attention mechanism and replacing the standard convolutional layer with depthwise separable convolution. This innovative approach aims to improve the efficiency and accuracy of short-term precipitation forecasting by improving feature extraction and data processing techniques. Evaluation and analysis of experimental data show that both models exhibit good predictive ability, with the SmaAT-UNet model outperforming ConvLSTM in terms of accuracy. The results show that the performance indicators of precipitation prediction, especially detection probability (POD) and the Critical Success index (CSI), show a downward trend with the extension of the prediction time. This trend highlights the inherent challenges of maintaining predictive accuracy over longer periods of time and highlights the superior performance and resilience of the SmaAT-UNet model under these conditions. Compared with the statistical forecasting method and numerical model forecasting method, its accuracy in short-term rainfall forecasting is improved.

Astragali Radix-Curcumae Rhizoma herb pair reduces the stemness of colorectal cancer cells through HIF-2α/ß-catenin pathway.

BACKGROUND: Colorectal cancer (CRC) is one of the most common causes of cancer-related mortality and significantly impairs quality of life. Astragali Radix-Curcumae Rhizoma (AC) is widely employed in the treatment of CRC in Chinese medicine, but the precise mechanisms remain unclear. PURPOSE: This study aimed to elucidate the mechanisms by which AC inhibits CRC progression. METHODS: The active components of AC were identified using UPLC-MS/MS analysis. An orthotopic transplantation colorectal tumor model was established in BALB/c mice using the CT26-Lucifer cell line to evaluate the effects of AC. Tumor volumes were monitored using IVIS imaging technology. Histological examination of tumor morphology was performed with hematoxylin and eosin (H&E) staining. Transcriptomic sequencing of mouse tumor samples was conducted to identify critical pathways and molecular targets. The impact of AC on cell viability and migration was assessed using CCK-8 and wound healing assays, respectively. To investigate the effects of AC on CRC cells, an in vitro hypoxic model was established using cobalt chloride (CoCl2), a hypoxia inducer. HIF-2α overexpression was achieved by constructing stable lentiviral vectors. Key targets identified from RNA-seq, such as c-Myc, Ki-67, ß-catenin, cleaved caspase 3, CD133, and CD44, were evaluated using western blotting, qRT-PCR, and immunofluorescence assays. Epithelial-Mesenchymal Transition (EMT) and spheroid cloning assays were employed to evaluate phenotypic changes in cancer stem cells. RESULTS: Twelve components of AC were identified. AC effectively inhibited CRC progression in vivo. Transcriptomic analysis highlighted hypoxic signaling as a significantly enriched pathway, implicating its role in suppressing CRC progression by AC. In the hypoxic model, AC inhibited the proliferation and migration of CRC cells in vitro. Furthermore, AC reduced cancer stemness by downregulating stemness markers, inhibiting EMT, and decreasing tumor sphere formation. The downregulation of hypoxic responses and the shift in stemness by AC involved attenuation of HIF-2α and WNT/ß-catenin signaling. CONCLUSION: This study provides the first evidence that AC reduces the stemness of CRC and the inhibition of the transition of CRC to stem-like cells by AC is closely related to the downregulation of the HIF-2α/ß-catenin pathway, especially under hypoxic conditions.

Heart Failure with Normal Natriuretic Peptide Levels and Preserved Ejection Fraction: A Prospective Clinical and Cardiac MRI Study.

Purpose To describe the clinical presentation, comprehensive cardiac MRI characteristics, and prognosis of individuals with predisposed heart failure with preserved ejection fraction (HFpEF). Materials and Methods This prospective cohort study (part of MISSION-HFpEF [Multimodality Imaging in the Screening, Diagnosis, and Risk Stratification of HFpEF]; NCT04603404) was conducted from January 1, 2019, to September 30, 2021, and included individuals with suspected HFpEF who underwent cardiac MRI. Participants who had primary cardiomyopathy and primary valvular heart disease were excluded. Participants were split into a predisposed HFpEF group, defined as HFpEF with normal natriuretic peptide levels based on an HFA-PEFF (Heart Failure Association Pretest Assessment, Echocardiography and Natriuretic Peptide, Functional Testing, and Final Etiology) score of 4 from the latest European Society of Cardiology guidelines, and an HFpEF group (HFA-PEFF score of ≥ 5). An asymptomatic control group without heart failure was also included. Clinical and cardiac MRI-based characteristics and outcomes were compared between groups. The primary end points were death, heart failure hospitalization, or stroke. Results A total of 213 participants with HFpEF, 151 participants with predisposed HFpEF, and 100 participants in the control group were analyzed. Compared with the control group, participants with predisposed HFpEF had worse left ventricular remodeling and function and higher systemic inflammation. Compared with participants with HFpEF, those with predisposed HFpEF, whether obese or not, were younger and had higher plasma volume, lower prevalence of atrial fibrillation, lower left atrial volume index, and less impaired left ventricular global longitudinal strain (-12.2% ± 2.8 vs -13.9% ± 3.1; P < .001) and early-diastolic global longitudinal strain rate (eGLSR, 0.52/sec ± 0.20 vs 0.57/sec ± 0.15; P = .03) but similar prognosis. Atrial fibrillation occurrence (hazard ratio [HR] = 3.90; P = .009), hemoglobin level (HR = 0.94; P = .001), and eGLSR (per 0.2-per-second increase, HR = 0.28; P = .002) were independently associated with occurrence of primary end points in participants with predisposed HFpEF. Conclusion Participants with predisposed HFpEF showed relatively unique clinical and cardiac MRI features, warranting greater clinical attention. eGLSR should be considered as a prognostic factor in participants with predisposed HFpEF. Keywords: Heart Failure with Preserved Ejection Fraction, Normal Natriuretic Peptide Levels, Cardiovascular Magnetic Resonance, Myocardial Strain, Prognosis Clinical trial registration no. NCT04603404 Supplemental material is available for this article. © RSNA, 2024.

Cellular elasticity in cancer: a review of altered biomechanical features.

A large number of studies have shown that changes in biomechanical characteristics are an important indicator of tumor transformation in normal cells. Elastic deformation is one of the more studied biomechanical features of tumor cells, which plays an important role in tumourigenesis and development. Altered cell elasticity often brings many indications. This manuscript reviews the effects of altered cellular elasticity on cell characteristics, including adhesion viscosity, migration, proliferation, and differentiation elasticity and stiffness. Also, the physical factors that may affect cell elasticity, such as temperature, cell height, cell-viscosity, and aging, are summarized. Then, the effects of cell-matrix, cytoskeleton, in vitro culture medium, and cell-substrate with different three-dimensional structures on cell elasticity during cell tumorigenesis are outlined. Importantly, we summarize the current signaling pathways that may affect cellular elasticity, as well as tests for cellular elastic deformation. Finally, we summarize current hybrid materials: polymer-polymer, protein-protein, and protein-polymer hybrids, also, nano-delivery strategies that target cellular resilience and cases that are at least in clinical phase 1 trials. Overall, the behavior of cancer cell elasticity is modulated by biological, chemical, and physical changes, which in turn have the potential to alter cellular elasticity, and this may be an encouraging prediction for the future discovery of cancer therapies.

Epigenetic editing of BRCA1 promoter increases cisplatin and olaparib sensitivity of ovarian cancer cells.

Drug resistance is the primary contributor to the high mortality rate of ovarian cancer (OC). The loss of BRCA1/2 function is linked to drug sensitivity in OC cells. The aim of this study is to enhance the drug sensitivity of OC cells by inducing BRCA1 dysfunction through promoter epigenetic editing. Epigenetic regulatory regions within the BRCA1 promoter, affecting gene expression, were initially discerned through analysis of clinical samples. Subsequently, we designed and rigorously validated epigenetic editing tools. Ultimately, we evaluated the cisplatin and olaparib sensitivity of the OC cells after editing. The BRCA1 promoter contains two CpG-rich regions, with methylation of the region covering the transcription start site (TSS) strongly correlating with transcription and influencing OC development, prognosis, and homologous recombination (HR) defects. Targeting this region in OC cells using our designed epigenetic editing tools led to substantial and persistent DNA methylation changes, accompanied by significant reductions in H3K27ac histone modifications. This resulted in a notable suppression of BRCA1 expression and a decrease in HR repair capacity. Consequently, edited OC cells exhibited heightened sensitivity to cisplatin and olaparib, leading to increased apoptosis rates. Epigenetic inactivation of the BRCA1 promoter can enhance cisplatin and olaparib sensitivity of OC cells through a reduction in HR repair capacity, indicating the potential utility of epigenetic editing technology in sensitization therapy for OC.

Eugenol-loaded polyurethane gelatin dressing for efficient angiogenesis and antibacterial effects in refractory diabetic wound defect healing.

The amelioration of refractory diabetic ulcers presents a formidable conundrum on a global scale, attributable to the elevated peril of contagion and protracted convalescence durations. Within the purlieus of this reparative epoch, the deployment of efficacious wound coverings endowed with both angiogenesis and antibacterial attributes is of paramount significance. Hydrogel wound dressings are distinguished by their elevated biocompatibility, adhesive tenacity, and innate regenerative capacity. Eugenol, a substance distilled from the blossoms of the lilac, serves as a precursor to metformin and is known to impede the genesis of reactive oxygen species. Although its antibacterial effects have been extensively chronicled, the angiogenic ramifications of eugenol within the context of wound remediation remain under-investigated. This research aimed to evaluate the effectiveness of eugenol-infused hydrogel as a wound dressing material. In this context, polyurethane gelatin (PG) was combined with eugenol at concentrations of 0.5% and 1%, creating PG-eugenol hydrogel mixtures with specific mass ratios for both in vivo and in vitro assessments. The in vivo studies indicated that hydrogels infused with eugenol expedited diabetic wound healing by fostering angiogenesis. Enhanced healing was noted, attributed to improved antibacterial and angiogenic properties, increased cell proliferation, tissue regeneration, and re-epithelialization. The in vitro analyses revealed that eugenol-enriched hydrogels stimulated the growth of fibroblasts (HFF-1) and human umbilical vein endothelial cells (HUVECs) and exhibited antibacterial characteristics. This investigation confirms the potential of eugenol-laden hydrogels in effectively treating diabetic wound defects.

[Astragali Radix-Curcumae Rhizoma inhibits colon cancer progression and enhances 5-FU efficacy by regulating hypoxia-inducible factors and tumor stem cells].

The animal and cell models were used in this study to investigate the mechanism of Astragali Radix-Curcumae Rhizoma(HQEZ) in inhibiting colon cancer progression and enhancing the efficacy of 5-fluorouracil(5-FU) by regulating hypoxia-inducible factors and tumor stem cells. The animal model was established by subcutaneous transplantation of colon cancer HCT116 cells in nude mice, and 24 successfully modeled mice were randomized into model, 5-FU, HQEZ, and 5-FU+HQEZ groups. The tumor volume was measured every two days. Western blot was employed to measure the protein levels of epidermal growth factor receptor(EGFR), dihydropyrimidine dehydrogenase(DPYD), and thymidylate synthase(TYMS), the key targets of the hypoxic core region, as well as the hypoxia-inducible factors HIF-1α and HIF-2α and the cancer stem cell surface marker CD133 and SRY-box transcription factor 2(SOX2). The results of animal experiments showed that HQEZ slowed down the tumor growth and significantly increased the tumor inhibition rate of 5-FU. Compared with the model group, HQEZ significantly down-regulated the protein levels of EGFR and DPYD, and 5-FU+HQEZ significantly down-regulated the protein levels of EGFR and TYMS in tumors. Compared with the model group, HQEZ significantly down-regulated the protein levels of HIF-1α, HIF-2α, SOX2, and CD133 in the hypoxic core region. Compared with the 5-FU group, 5-FU+HQEZ lowered the protein levels of HIF-1α, HIF-2α, and SOX2. The cell experiments showed that the protein le-vels of HIF-1α and HIF-2α in HCT116 cells elevated significantly after low oxygen treatment. Compared with 5-FU(1.38 µmol·L~(-1)) alone, HQEZ(40 mg·mL~(-1)) and 5-FU+HQEZ significantly down-regulated the protein levels of HIF-1α, HIF-2α, and TYMS. In conclusion, HQEZ can inhibit the expression of hypoxia-responsive molecules in colon cancer cells and reduce the properties of cancer stem cells, thereby enhancing the therapeutic effect of 5-FU on colon cancer.

Effect of a novel dwarfing mutant site on chromosome 4B on agronomic traits in common wheat.

The introduction of dwarfing genes triggered a wave of "green revolution". A number of wheats dwarfing genes have been reported in previous studies, and only a small fraction of these have been applied to production practices. Therefore, the development of novel dwarfing genes for wheat is of great value. In this study, a novel dwarfing site, Rht-yz, identified in the Yanzhan mutation, is located on chromosome 4B (30-33MB) and its mechanism of action is different from that of Rht-B1b (C-T mutation), but whether it affects the Rht-B1a (TraesCS4B02G043100) or other genes is unclear. Exogenously applied GA3 experiments showed that Rht-yz is one of the gibberellin-insensitive dwarf genes. The effects of the dwarf gene Rht-yz on agronomic traits in wheat were evaluated in the field using Yanzhan, Yanzhan mutations, F2:3 and F3:4 lines. The results showed that Rht-yz improved lodging resistance by reducing plant height, increasing diameter, wall thickness and mechanical strength of the basal stem. In terms of yield traits, Rht-yz had negative effects on tiller number plant-1, biomass plant-1 and yield plant-1, but had no significant effect on harvest index, 1000-kernel weight and spike traits. In addition, Rht-yz significantly increased crude protein, wet gluten and starch content. Therefore, the rational use of the new dwarfing site Rht-yz has potential and value in dwarf wheat breeding.

A Molecular Typing Method for Invasive Breast Cancer by Serum Raman Spectroscopy.

BACKGROUND: The incidence of breast cancer ranks highest among cancers and is exceedingly heterogeneous. Immunohistochemical staining is commonly used clinically to identify the molecular subtype for subsequent treatment and prognosis. PURPOSE: Raman spectroscopy and support vector machine (SVM) learning algorithm were utilized to identify blood samples from breast cancer patients in order to investigate a novel molecular typing approach. METHOD: Tumor tissue coarse needle aspiration biopsy samples, and peripheral venous blood samples were gathered from 459 invasive breast cancer patients admitted to the breast department of Sichuan Cancer Hospital between June 2021 and September 2022. Immunohistochemical staining and in situ hybridization were performed on the coarse needle aspiration biopsy tissues to obtain their molecular typing pathological labels, including: 70 cases of Luminal A, 167 cases of Luminal B (HER2-positive), 57 cases of Luminal B (HER2-negative), 84 cases of HER2-positive, and 81 cases of triple-negative. Blood samples were processed to obtained Raman spectra taken for SVM classification models establishment with machine algorithms (using 80% of the sample data as the training set), and then the performance of the SVM classification models was evaluated by the independent validation set (20% of the sample data). RESULTS: The AUC values of SVM classification models remained above 0.85, demonstrating outstanding model performance and excellent subtype discrimination of breast cancer molecular subtypes. CONCLUSION: Raman spectroscopy of serum samples can promptly and precisely detect the molecular subtype of invasive breast cancer, which has the potential for clinical value.

Variability of BMP-2 content in DBM products derived from different long bone.

Demineralized bone matrix (DBM) has been regarded as an ideal bone substitute as a native carrier of bone morphogenetic proteins (BMPs) and other growth factors. However, the osteoinductive properties diverse in different DBM products. We speculate that the harvest origin further contributing to variability of BMPs contents in DBM products besides the process technology. In the study, the cortical bone of femur, tibia, humerus, and ulna from a signal donor were prepared and followed demineralizd into DBM products. Proteins in bone martix were extracted using guanidine-HCl and collagenase, respectively, and BMP-2 content was detected by sandwich enzyme-linked immunosorbent assay (ELISA). Variability of BMP-2 content was found in 4 different DBM products. By guanidine-HCl extraction, the average concentration in DBMs harvested from ulna, humerus, tibia, and femur were 0.613 ± 0.053, 0.848 ± 0.051, 3.293 ± 0.268, and 21.763 ± 0.344, respectively (p < 0.05), while using collagenase, the levels were 0.089 ± 0.004, 0.097 ± 0.004, 0.330 ± 0.012, and 1.562 ± 0.008, respectively (p < 0.05). In general, the content of BMP-2 in long bones of Lower limb was higher than that in long bones of upper limb, and GuHCl had remarkably superior extracted efficiency for BMP-2 compared to collagenase. The results suggest that the origin of cortical bones harvested to fabricate DBM products contribute to the variability of native BMP-2 content, while the protein extracted method only changes the measured values of BMP-2.

Homotherapy-for-heteropathy of Bupleurum Chinense DC.-Scutellaria baicalensis Georgi in treating depression and colorectal cancer: A network pharmacology and animal model approach.

ETHNOPHARMACOLOGICAL RELEVANCE: Bupleurum chinense DC.-Scutellaria baicalensis Georgi (BS) is a classic drug pair that has good clinical effects on depression and many tumors. However, the concurrent targeting mechanism of how the aforementioned drug pair is valid in the two distinct diseases, has not been clarified yet. AIM OF THE STUDY: The components of BS were detected by LC-MS, combined with network pharmacology to explore the active ingredients and common targeting mechanism of its multi-pathway regulation of BS in treating depression and CRC, and to validate the dual effects of BS using the CUMS mice model and orthotopic transplantation tumor mice model of CRC. RESULTS: Twenty-nine components were screened, 84 common gene targets were obteined, and the top 5 key targets including STAT3, PIK3R1, PIK3CA, AKT1, IL-6 were identified by PPI network. GO and KEGG analyses revealed that PI3K/AKT and JAK/STAT signaling pathways might play a crucial role of BS in regulating depression and CRC. BS significantly modulated CUMS-induced depressive-like behavior, attenuated neuronal damage, and reduced serum EPI and NE levels in CUMS model mice. BS improved the pathological histological changes of solid tumors and liver tissues and inhibited solid tumors and liver metastases in tumor-bearing mice. BS significantly decreased the proteins' expression of IL-6, p-JAK2, p-STAT3, p-PI3K, p-AKT1 in hippocampal tissues and solid tumors, and regulated the levels of IL-2, IL-6 and IL-10 in serum of two models of mice. CONCLUSION: BS can exert dual antidepressant and anti-CRC effects by inhibiting the expression of IL-6/JAK2/STAT3 and PI3K/AKT pathway proteins and regulating the release of inflammatory cytokines.

Genome sequences and population genomics reveal climatic adaptation and genomic divergence between two closely related sweetgum species.

Understanding the genetic basis of population divergence and adaptation is an important goal in population genetics and evolutionary biology. However, the relative roles of demographic history, gene flow, and/or selective regime in driving genomic divergence, climatic adaptation, and speciation in non-model tree species are not yet fully understood. To address this issue, we generated whole-genome resequencing data of Liquidambar formosana and L. acalycina, which are broadly sympatric but altitudinally segregated in the Tertiary relict forests of subtropical China. We integrated genomic and environmental data to investigate the demographic history, genomic divergence, and climatic adaptation of these two sister species. We inferred a scenario of allopatric species divergence during the late Miocene, followed by secondary contact during the Holocene. We identified multiple genomic islands of elevated divergence that mainly evolved through divergence hitchhiking and recombination rate variation, likely fostered by long-term refugial isolation and recent differential introgression in low-recombination genomic regions. We also found some candidate genes with divergent selection signatures potentially involved in climatic adaptation and reproductive isolation. Our results contribute to a better understanding of how late Tertiary/Quaternary climatic change influenced speciation, genomic divergence, climatic adaptation, and introgressive hybridization in East Asia's Tertiary relict flora. In addition, they should facilitate future evolutionary, conservation genomics, and molecular breeding studies in Liquidambar, a genus of important medicinal and ornamental values.