Deep Learning-Based Stratification of Gastric Cancer Patients from Hematoxylin and Eosin-Stained Whole Slide Images by Predicting Molecular Features for Immunotherapy Response.

Determining the molecular characteristics of cancer patients is crucial for optimal immunotherapy decisions. The aim of this study was to screen immunotherapy beneficiaries by predicting key molecular features from hematoxylin and eosin-stained images based on deep learning models. An independent data set from Asian gastric cancer patients was included for external validation. In addition, a segmentation model (Horizontal-Vertical Network) was used to quantify the cellular composition of tumor stroma. The model performance was evaluated by measuring the area under the curve (AUC). The tumor extraction model achieved an AUC of 0.9386 and 0.9062 in the internal and external test sets, respectively. The stratification model could predict the immunotherapy-sensitive subtypes (AUC range, 0.8685 to 0.9461), the genetic mutations (AUC range, 0.8283 to 0.9225), and the pathway activity (AUC range, 0.7568 to 0.8612) fairly accurately. In external validation, the prediction performance of Epstein-Barr virus and programmed cell death ligand 1 expression status achieved AUCs of 0.7906 and 0.6384, respectively. The segmentation model identified a relatively high proportion of inflammatory cells and connective cells in some immunotherapy-sensitive subtypes. The deep learning-based models potentially may serve as a valuable tool to screen for the beneficiaries of immunotherapy in gastric cancer patients.

Effect of preoperative oral carbohydrates on insulin resistance in patients undergoing laparoscopic cholecystectomy: a randomized controlled trial.

PURPOSE: The present research seeks to clarify the consequences of two specific preoperative oral carbohydrate (POC) amounts on insulin resistance (IR) and stomach evacuation in laparoscopic cholecystectomy (LC) patients. METHODS: A total of 129 patients set for elective LC procedures were randomly assigned to a control group (C, n = 45), a 200 mL POC group (P1, n = 42), and a 400 mL POC group (P2, n = 42). The C group was fasted from midnight until surgery, whereas the P1 and P2 groups received their respective carbohydrate volumes 2-4 h before anesthesia. Fasting blood glucose, insulin, and glucagon concentrations were measured at three junctures. IR metrics were derived by employing the homeostasis model assessment. Gastric volume was measured before anesthesia using gastric ultrasound. Inter-group comparisons included IR indicators, subjective comfort scores, and hemodynamic data. RESULTS: At T2, the C group exhibited reduced glucose concentrations compared to the P2 group (4.73 ± 0.64 vs. 5.26 ± 1.02 mmol/L, p < 0.05). The Perlas grading indicated that grade 1 was more prevalent in the P2 group than in the P1 and C groups (18 [42.9%] vs. 6 [14.3%] and 1 [2.2%], p < 0.05). Additionally, thirst and hunger metrics for the P2 group were notably reduced compared to the C group at both T2 and T3. CONCLUSION: Administering either 200 mL or 400 mL of carbohydrates 2-4 h pre-surgery had no detectable impact on IR or gastric volume in LC patients. TRIAL REGISTRATION: ChiCTR, ChiCTR2200065648. Registered January 13, 2023, http://www.chictr.org.cn .

Effects of Preoperative Oral Carbohydrates on Recovery After Laparoscopic Cholecystectomy: A Meta-analysis of Randomized Controlled Trials.

PURPOSE: The objective of this meta-analysis was to evaluate the efficacy of administering preoperative oral carbohydrates (CHO) compared to a control treatment in improving postoperative recovery outcomes for patients undergoing laparoscopic cholecystectomy (LC). DESIGN: A meta-analysis of randomized controlled trials. METHODS: Through systematic searches in PubMed, Embase, and the Cochrane Library, randomized controlled trials focusing on preoperative oral carbohydrates for patients undergoing LC were collected. Data analysis was conducted using the Revman 5.3 software. FINDINGS: The meta-analysis incorporated 19 randomized studies, with a total of 1,568 participants. Meta-analysis results indicated that patients receiving CHO reported notably lower postoperative pain compared to those fasting (P = .006) or on placebo (P = .003). Furthermore, a significant reduction in preoperative hunger was observed in the CHO group compared to the controls (P = .002). A notable difference was also identified in the postoperative Homeostasis Model Assessment-IR changes between the CHO and control groups (P = .02). No significant variations were observed in thirst, postoperative nausea and vomiting, insulin level alterations, glucose level changes, duration of hospital stay, or recovery quality. CONCLUSIONS: Preoperative oral carbohydrates may alleviate hunger and pain, and attenuate postoperative insulin resistance more effectively than either overnight fasting or placebo in patients undergoing LC.

Progress in the study of intragastric occupancy device for weight reduction. / èƒƒå† å å®¹è£ ç½®å‡é‡çš„ç ”ç©¶è¿›å±•.

Obesity is a global public health problem that imposes a heavy economic burden on society. The current main strategies for treating obesity include lifestyle interventions, pharmacological treatments, endoscopic treatments and metabolic surgery. With the development of medical technology, weight reduction by intragastric occupancy devices represented by intragastric balloons and intragastric capsules are gradually emerging. Intragastric balloons are used to reduce weight by occupying the volume of the stomach with balloons filled with different volumes of gas or liquid, among which ReShape, Orbera, Obalon, Elipse and Spatz balloons are gradually used in patients with mild to moderate obesity due to their non-invasive, high safety and reusable advantages. Intragastric capsules are recommended in overweight and obese patients for weight loss through hydrogels with transient superabsorbent swelling properties and completely noninvasive. Both approaches achieve weight loss by limiting gastric volume, increasing satiety and reducing food intake. Despite the presence of adverse gastrointestinal events associated with nausea, vomiting, and abdominal distention, they offer new ideas for the non-invasive clinical treatment of obesity.

A Dynamic RCS and Noise Prediction and Reduction Method of Coaxial Tilt-Rotor Aircraft Based on Phase Modulation.

For tilt-rotor aircraft with coaxial rotors (coaxial rotor aircraft), reduction of radar cross section as well as acoustic noise can be essential for stealth design, and the rotation of the coaxial rotors can have an influence on noise and dynamic radar cross section (RCS) characteristics. In this paper, an approach to the prediction of both the sound pressure level (SPL) of noise and the dynamic RCS of coaxial-tilt aircraft is carried out, based on the theories of the FW-H equation, the physics optics method (PO) and the physical theory of diffraction (PTD) method. In order to deal with the rotating parts (mainly including coaxial rotors), a generated rotation matrix (GRM) is raised, aiming at giving a universal formula for the time-domain grid coordinate transformation of all kinds of rotation parts with arbitrary rotation centers and rotation axis directions. Moreover, a compass-scissors model (CSM) reflecting the phase characteristics of coaxial rotors is established, and a method of noise reduction and RCS reduction based on the phase modulation method is put forward in this paper. The simulation results show that with proper CSM parameter combinations, the reduction of noise SPL can reach approximately 3~15 dB and the reduction of dynamic RCS can reach 1.6 dBsm at most. The dynamic RCS and noise prediction and reduction method can be meaningful for the radar-acoustic stealth design of coaxial tilt-rotor aircrafts.

Study on Quantum Radar Detection Probability Based on Flying-Wing Stealth Aircraft.

The development of quantum radar technology presents a challenge to stealth targets, so it is necessary to study the quantum detection probability. In this study, an analytical expression of the quantum radar cross section (QRCS) for complex targets is presented. Based on this QRCS expression, a calculation method for the detection probability for quantum radar is creatively proposed. Moreover, a self-designed flying-wing stealth aircraft is adopted to obtain the detection probability distributions of the conventional radar and the quantum radar in different directions. As revealed by the result of this study, the detection probabilities of the quantum radar and the conventional radar are significantly different, and the detection probability of the quantum radar has obvious advantages in most regions with a certain distance.

Identification of differential proteomics in Epstein-Barr virus-associated gastric cancer and related functional analysis.

BACKGROUND: Epstein-Barr virus-associated gastric cancer (EBVaGC) is the most common EBV-related malignancy. A comprehensive research for the protein expression patterns in EBVaGC established by high-throughput assay remains lacking. In the present study, the protein profile in EBVaGC tissue was explored and related functional analysis was performed. METHODS: Epstein-Barr virus-encoded RNA (EBER) in situ hybridization (ISH) was applied to EBV detection in GC cases. Data-independent acquisition (DIA) mass spectrometry (MS) was performed for proteomics assay of EBVaGC. Functional analysis of identified proteins was conducted with bioinformatics methods. Immunohistochemistry (IHC) staining was employed to detect protein expression in tissue. RESULTS: The proteomics study for EBVaGC was conducted with 7 pairs of GC cases. A total of 137 differentially expressed proteins in EBV-positive GC group were identified compared with EBV-negative GC group. A PPI network was constructed for all of them, and several proteins with relatively high interaction degrees could be the hub genes in EBVaGC. Gene enrichment analysis showed they might be involved in the biological pathways related to energy and biochemical metabolism. Combined with GEO datasets, a highly associated protein (GBP5) with EBVaGC was screened out and validated with IHC staining. Further analyses demonstrated that GBP5 protein might be associated with clinicopathological parameters and EBV infection in GC. CONCLUSIONS: The newly identified proteins with significant differences and potential central roles could be applied as diagnostic markers of EBVaGC. Our study would provide research clues for EBVaGC pathogenesis as well as novel targets for the molecular-targeted therapy of EBVaGC.

Pre-marked chromatin and transcription factor co-binding shape the pioneering activity of Foxa2.

Pioneer transcription factors (PTF) can recognize their binding sites on nucleosomal DNA and trigger chromatin opening for recruitment of other non-pioneer transcription factors. However, critical properties of PTFs are still poorly understood, such as how these transcription factors selectively recognize cell type-specific binding sites and under which conditions they can initiate chromatin remodelling. Here we show that early endoderm binding sites of the paradigm PTF Foxa2 are epigenetically primed by low levels of active chromatin modifications in embryonic stem cells (ESC). Priming of these binding sites is supported by preferential recruitment of Foxa2 to endoderm binding sites compared to lineage-inappropriate binding sites, when ectopically expressed in ESCs. We further show that binding of Foxa2 is required for chromatin opening during endoderm differentiation. However, increased chromatin accessibility was only detected on binding sites which are synergistically bound with other endoderm transcription factors. Thus, our data suggest that binding site selection of PTFs is directed by the chromatin environment and that chromatin opening requires collaboration of PTFs with additional transcription factors.

Clinical characteristics of 116 hospitalized patients with COVID-19 in Wuhan, China: a single-centered, retrospective, observational study.

BACKGROUND: A cluster of acute respiratory illness, now known as Corona Virus Disease 2019 (COVID-19) caused by 2019 novel coronavirus (SARS-CoV-2), has become a global pandemic. Aged population with cardiovascular diseases are more likely be to infected with SARS-CoV-2 and result in more severe outcomes and elevated case-fatality rate. Meanwhile, cardiovascular diseases have a high prevalence in the middle-aged and elderly population. However, despite of several researches in COVID-19, cardiovascular implications related to it still remains largely unclear. Therefore, a specific analysis in regard to cardiovascular implications of COVID-19 patients is in great need. METHODS: In this single-centered, retrospective, observational study, 116 patients with laboratory-confirmed COVID-19 were enrolled, who admitted to the General Hospital of Central Theater Command (Wuhan, China) from January 20 to March 8, 2020. The demographic data, underlying comorbidities, clinical symptoms and signs, laboratory findings, chest computed tomography, treatment measures, and outcome data were collected from electronic medical records. Data were compared between non-severe and severe cases. RESULTS: Of 116 hospitalized patients with COVID-19, the median age was 58.5 years (IQR, 47.0-69.0), and 36 (31.0%) were female. Hypertension (45 [38.8%]), diabetes (19 [16.4%]), and coronary heart disease (17 [14.7%]) were the most common coexisting conditions. Common symptoms included fever [99 (85.3%)], dry cough (61 [52.6%]), fatigue (60 [51.7%]), dyspnea (52 [44.8%]), anorexia (50 [43.1%]), and chest discomfort (50 [43.1%]). Local and/or bilateral patchy shadowing were the typical radiological findings on chest computed tomography. Lymphopenia (lymphocyte count, 1.0 × 109/L [IQR, 0.7-1.3]) was observed in 66 patients (56.9%), and elevated lactate dehydrogenase (245.5 U/L [IQR, 194.3-319.8]) in 69 patients (59.5%). Hypokalemia occurred in 24 (20.7%) patients. Compared with non-severe cases, severe cases were older (64.0 years [IQR, 53.0-76.0] vs 56.0 years [IQR, 37.0-64.0]), more likely to have comorbidities (35 [63.6%] vs 24 [39.3%]), and more likely to develop acute cardiac injury (19 [34.5%] vs 4 [6.6%]), acute heart failure (18 [32.7%] vs 3 [4.9%]), and ARDS (20 [36.4%] vs 0 [0%]). During hospitalization, the prevalence of new onset hypertension was significantly higher in severe patients (55.2% vs 19.0%) than in non-severe ones. CONCLUSIONS: In this single-centered, retrospective, observational study, we found that the infection of SARS-CoV-2 was more likely to occur in middle and aged population with cardiovascular comorbidities. Cardiovascular complications, including new onset hypertension and heart injury were common in severe patients with COVID-19. More detailed researches in cardiovascular involvement in COVID-19 are urgently needed to further understand the disease.

Aberrantly methylated-differentially expressed genes and pathways in Epstein-Barr virus-associated gastric cancer.

Aim: To identify the methylated-differentially expressed genes (MDEGs) that may serve as diagnostic markers and therapeutic targets in Epstein-Barr virus-associated gastric cancer (EBVaGC) and to explore the methylation-based pathways for elucidating biological mechanisms of EBVaGC. Materials & methods: Gene expression and methylation profiles were downloaded from GEO database. MDEGs were identified by GEO2R. Pathway enrichment analyses were conducted based on DAVID database. Hub genes were identified by Cytoscape, which were further verified by The Cancer Genome Atlas database. Results: A total of 367 hypermethylated, lowly expressed genes were enriched in specific patterns of cell differentiation. 31 hypomethylated, highly expressed genes demonstrated enrichment in regulation of immune system process. After validation using The Cancer Genome Atlas database, seven genes were confirmed to be significantly different hub genes in EBVaGC. Conclusion: EBVaGC-specific MDEGs and pathways can be served as potential biomarkers for precise diagnosis and treatment of EBVaGC and provide novel insights into the mechanisms involved.

Activation of the STAT3/microRNA-21 pathway participates in angiotensin II-induced angiogenesis.

Angiotensin II (AngII) facilitates angiogenesis that is associated with the continuous progression of atherosclerotic plaques, but the underlying mechanisms are still not fully understood. Several microRNAs (miRNAs) have been shown to promote angiogenesis; however, whether miRNAs play a crucial role in AngII-induced angiogenesis remains unclear. This study evaluated the functional involvement of miRNA-21 (miR-21) in the AngII-mediated proangiogenic response in human microvascular endothelial cells (HMECs). We found that AngII exerted a proangiogenic role, indicated by the promotion of proliferation, migration, and tube formation in HMECs. Next, miR-21 was found to be upregulated in AngII-treated HMECs, and its specific inhibitor potently blocked the proangiogenic effects of AngII. Subsequently, we focused on the constitutive activation of STAT3 in the AngII-mediated proangiogenic process. Bioinformatic analysis indicated that STAT3 acted as a transcription factor initiating miR-21 expression, which was verified by ChIP-PCR. A reporter assay further identified three functional binding sites of STAT3 in the miR-21 promoter region. Moreover, phosphatase and tensin homolog (PTEN) was recognized as a target of miR-21, and STAT3 inhibition restored AngII-induced reduction in PTEN. Similarly, the STAT3/miR-21 axis was shown to mediate AngII-provoked angiogenesis in vivo, which was demonstrated by using the appropriate inhibitors. Our data suggest that AngII was involved in proangiogenic responses through miR-21 upregulation and reduced PTEN expression, which was, at least in part, linked to STAT3 signaling. The present study provides novel insights into AngII-induced angiogenesis and suggests potential treatment strategies for attenuating the progression of atherosclerotic lesions and preventing atherosclerosis complications.

[Inhibition of SCD1 Activity Blocks Cell Cycle Progression and Impairs Proliferation in Breast Cancer Cells].

OBJECTIVE: To investigate the expression of stearoyl-CoA desaturase-1 (SCD1) in breast cancer cell lines. To analyze the effect of inhibiting SCD1 activity on the proliferation and cell cycle of MCF-7 breast cancer cell and its mechanism. METHODS: The expression of SCD1 protein were detected by Western blot techniques in breast cancer cell lines and humanskin fibroblasts.Cell viability of MCF-7 cells treated with MF-438 was measured using MTS assay and IC50 value was calculated.The distribution of cell cycle was determined by PI staining using flow cytometry.The expression of Cyclin D1 was detected by Western blot. The expression of Akt, pAkt, pAMPK and pACC were also detected by Western blot. RESULTS: The expression level of SCD1 in MCF-7 and MDA-MB-231 cells was significantly higher than that in HSF cells (P < 0.05).MF-438 showed a significant dose-dependent proliferation inhibition effect on MCF-7 cells cultured in low serum at a concentration ranging from 100 nmol/L to 100 µmol/L with an IC50 value of (3.9±0.45) µmol/L. After intervention of 5 µmol/L MF-438 in MCF-7 cells, the proportion of cells in S phase and G2/M phase was significantly decreased (P < 0.01), the proportion of cells in G0/G1 phase increased (P < 0.01), and the expression of Cyclin D1 was significantly decreased (P < 0.05); Meanwhile, the expression of pAkt and pAkt/Akt value were significantly decreased (P < 0.05) and the expression of pAMPK and pACC levels were significantly increased (P < 0.05). CONCLUSIONS: SCD1 plays an important role in the occurrence and development of breast cancer. Inhibition of SCD1 activity can inhibit cell cycle progression and impair cell proliferation by down-regulating the Akt pathway and activating the AMPK pathway. Further research on SCD1 is expected to provide a new target for molecular targeted therapy of breast cancer.

Key elements involved in Epstein-Barr virus-associated gastric cancer and their network regulation.

BACKGROUND: The molecular mechanism of Epstein-Barr virus (EBV)-associated gastric cancer (EBVaGC) remains elusive. A collection of molecular regulators including transcription factor and noncoding RNA (ncRNAs) may affect the carcinogenesis of EBVaGC by regulating the expression and function of key genes. In this study, integration of multi-level expression data and bioinformatics approach was used to identify key elements and their interactions involved in mechanism of EBVaGC and their network regulation. METHODS: Data of the gene expression profiling data sets (GSE51575) was downloaded from GEO database. Differentially expressed genes between EBVaGC and normal samples were identified by GEO2R. Gene ontology and pathway enrichment analyses were performed using R packages Cluster profiler. STRING database was used to find interacting proteins between different genes. Transcription factors in differentially expressed genes were obtained from TF Checkpoint database. Using Cytoscape, we built transcription factor regulation network. miRNAs involved in the gene-interacting proteins and the miRNA-targeted lncRNA were predicted through miRWalk. Using ViRBase, EBV related miRNA regulation network was built. Overlapping genes and regulators of the above three networks were further identified, and the cross network was constructed using Cytoscape software. Moreover, the differential expressions of the target genes and transcription factors in the cross network were explored in different molecular subtypes of GC using cBioPortal. By histological verification, the expression of two main target genes in the cross network were further analyzed. RESULTS: A total of 104 genes showed differential expressions between EBVaGC and normal tissues, which were associated with digestion, G-protein coupled receptor binding, gastric acid secretion, etc. Pathway analysis showed that the differentially expressed genes were mainly enriched in gastric acid secretion and protein digestion and absorption. Using STRING dataset, a total of 54 proteins interacted with each other. Based on the transcription factor network, the hub transcription factors IRX3, NKX6-2, PTGER3 and SMAD5 were identified to regulate their target genes SST and GDF5, etc. After screening and matching in miRwalk datasets, a ceRNA network was established, in which the top five miRNAs were hsa-miR-4446-3p, hsa-miR-5787, hsa-miR-1915-3p, hsa-miR-335-3p and hsa-miR-6877-3p, and the top two lncRNAs were RP5-1039K5.19 and TP73-AS1. According to the EBV related miRNA regulation network, CXCL10 and SMAD5 were found to be regulated by EBV-miR-BART1-3p and EBV-mir-BART22, respectively. By overlapping the three networks, CXCL10, GDF5, PTGER3, SMAD5, miR-6877-3p, RP5-1039K5.19, TP73-AS1, EBV-miR-BART1-3p and EBV-mir-BART22 were found to be key elements of regulation mechanism of EBVaGC. CXCL10, GDF5, PTGER3 and SMAD5 were also differentially expressed among the four molecular subtypes of GC. The histological verification experiment showed differential expressions of the two main target genes GDF5 and CXCL10 between EBVaGC and non-tumor tissues as well as EBVnGC. CONCLUSION: In the current study, our results revealed key elements and their interactions involved in EBVaGC. Some hub transcription factors, miRNAs, lncRNAs and EBV related miRNAs were observed to regulate their target genes. Overlapping genes and regulators were observed in diverse regulation networks, such as CXCL10, GDF5, PTGER3, SMAD5, miR-6877-3p, RP5-1039K5.19, TP73-AS1, EBV-miR-BART1-3p and EBV-mir-BART22. Moreover, CXCL10, GDF5, PTGER3 and SMAD5 were also differentially expressed among the four molecular subtypes of GC. The histological verification experiment showed differential expressions of the two main target genes GDF5 and CXCL10 between EBVaGC and non-tumor tissues as well as EBVnGC. Therefore, the identified key elements and their network regulation may be specifically involved in EBVaGC mechanisms.

Expression of DDB2 Protein in the Initiation, Progression, and Prognosis of Colorectal Cancer.

BACKGROUND: Damage-specific DNA binding protein 2 (DDB2) is implicated in the recognition of DNA damage and the initiation of nucleotide excision repair process. The aim of this study was to explore the role of DDB2 in the initiation, progression, and prognosis of colorectal cancer (CRC). METHODS: Totally tissues of 300 CRC and 300 adjacent, 267 colorectal adenoma (CRA) and 214 normal (NOR) were collected. The expression of DDB2 protein was detected by immunohistochemical staining. RESULTS: DDB2 protein was highly expressed in CRC and CRA compared with NOR (P < 0.001, respectively) in the dynamic sequence of NOR → CRA → CRC; CRC tissue demonstrated increased DDB2 expression compared with non-tumor adjacent tissues (P < 0.001). DDB2 expression was higher in T1-T2 than that in T3-T4 in CRC (P = 0.023); cloddy/nested CRC demonstrated increased DDB2 expression than infiltrative CRC (P = 0.007). Survival analysis showed that high DDB2 expression was associated with favorable survival in colon cancer (adjusted HR 0.20, 95% CI 0.06-0.72, P = 0.014) and female CRC patients (adjusted HR 0.27, 95% CI 0.08-0.92, P = 0.036). CONCLUSION: DDB2 protein expression was associated with the initiation, progression, and prognosis of CRC, and might function as a tumor biomarker for the diagnosis and prognosis of CRC.

Roles of High Mobility Group Box 1 in Cardiovascular Calcification.

Calcific disease of the cardiovascular system, including atherosclerotic calcification, medial calcification in diabetes and calcific aortic valve disease, is an important risk factor for many adverse cardiovascular events such as ischemic cardiac events and subsequent mortality. Although cardiovascular calcification has long been considered to be a passive degenerative occurrence, it is now recognized as an active and highly regulated process that involves osteochondrogenic differentiation, apoptosis and extracellular vesicle release. Nonetheless, despite numerous studies on the pathogenesis of cardiovascular calcification, the underlying mechanisms remain poorly understood. High mobility group box 1 (HMGB1), a nuclear protein bound to chromatin in almost all eukaryotic cells, acts as a damage-associated molecular pattern (DAMP) when released into the extracellular space upon cell activation, injury or death. Moreover, HMGB1 also functions as a bone-active cytokine participating in bone remodeling and ectopic calcification pathogenesis. However, studies on the roles of HMGB1 in promoting cardiovascular calcification are limited to date, and the mechanisms involved are still unclear. In this review, we summarize recent studies investigating the mechanism of cardiovascular calcification and discuss multiple roles of HMGB1 in its development.

Quantitative evaluation of acid flow behavior in fractures and optimization of design parameters based on acid wormhole filtration losses.

The technique of matrix acidification or acid fracturing is commonly utilized to establish communication with natural fractures during reservoir reconstruction. However, this process often encounters limitations due to filtration, which restricts the expansion of the primary acid-etching fracture. To address this issue, a computational model has been developed to simulate the expansion of an acid-etching wormhole by considering various factors such as formation process, injection duration, pressure build-up, and time-varying acid percolation rate. By analyzing the pumping displacement of acid-etching wormholes, this model provides valuable insights into the time-dependent quantities of acid percolation. It has been revealed that the filtration rate of acid-etching wormholes is strongly influenced by pumping displacement, viscosity, and concentration of the acid fluid used in stimulation as well as physical properties of the reservoir itself. Notably, viscosity plays a significant role in determining the effectiveness of acid fracturing especially in low-viscosity conditions. Acid concentration within 15% to 20% exhibits maximum impact on successful acid fracturing while concentrations below 15% or above 20% show no obvious effect. Furthermore, it was found that pumping displacement has a major influence on effective fracturing. However, beyond a certain threshold (> 5.0 m3/min), increased pumping displacement leads to slower etching distance for acids used in construction purposes. The simulation also provides real-time distribution analysis for acidity levels within eroded fractures during matrix-acidification processes and quantifies extent of chemical reactions between acids and rocks within these fractures thereby facilitating optimization efforts for design parameters related to matrix-acidification.

A distinct class of pan-cancer susceptibility genes revealed by an alternative polyadenylation transcriptome-wide association study.

Alternative polyadenylation plays an important role in cancer initiation and progression; however, current transcriptome-wide association studies mostly ignore alternative polyadenylation when identifying putative cancer susceptibility genes. Here, we perform a pan-cancer 3' untranslated region alternative polyadenylation transcriptome-wide association analysis by integrating 55 well-powered (n > 50,000) genome-wide association studies datasets across 22 major cancer types with alternative polyadenylation quantification from 23,955 RNA sequencing samples across 7,574 individuals. We find that genetic variants associated with alternative polyadenylation are co-localized with 28.57% of cancer loci and contribute a significant portion of cancer heritability. We further identify 642 significant cancer susceptibility genes predicted to modulate cancer risk via alternative polyadenylation, 62.46% of which have been overlooked by traditional expression- and splicing- studies. As proof of principle validation, we show that alternative alleles facilitate 3' untranslated region lengthening of CRLS1 gene leading to increased protein abundance and promoted proliferation of breast cancer cells. Together, our study highlights the significant role of alternative polyadenylation in discovering new cancer susceptibility genes and provides a strong foundational framework for enhancing our understanding of the etiology underlying human cancers.

N, N-bis (2-hydroxyethyl) malonamide based amidoxime functionalized polymer immobilized in biomembranes for highly selective adsorption of uranium(VI).

Amidoxime compounds have been widely used in metal separation and recovery because of their excellent chelating properties to metal ions, especially to uranium (VI). In this study, N, N-bis (2-hydroxyethyl) malonamide was obtained from ethanolamine and dimethyl malonate, and used to prepare a two-dimensional network polymer, then the obtained polymer was immobilized in an environmentally friendly chitosan biomembrane, which enhanced its stability and hydrophobicity, meanwhile the amidoxime functionalization was achieved by oximation reaction of bromoacetonitrile, the application of the material further extends to uranium (VI) separation in solutions. Due to the synergistic action of amide group and amidoxime group, poly (ethanolamine-malonamide) based amidoxime biomembranes (PEA-AOM) showed extraordinary adsorption effect on uranium (VI), among which the saturation adsorption capacity of PEA-AOM-2 was 748.64 mg/g. PEA-AOM-2 also had good reusability (following five cycles of adsorption-desorption, the recovery rate maintained at 88%) and selectivity for uranium (VI), showing satisfactory results in competitive ion coexistence system and simulated seawater experiments. This study demonstrated that PEA-AOM-2 provided a new option for uranium (VI) separation in complex environment and low-concentration uranium background.

125I Seed Brachytherapy for Refractory Loco-Regional Recurrence of Non-Anaplastic Thyroid Cancer.

PURPOSE: The purpose of this research was to evaluate the feasibility and efficacy of 125I seed brachytherapy as salvage treatment for recurrence from non-anaplastic thyroid cancer refractory to other modalities. METHODS: Between June 2006 and September 2019, fifteen patients with recurrent non-anaplastic thyroid cancer were treated with 125I seed brachytherapy. 125I seeds were implanted into the tumor under the guidance of CT and/or ultrasound images with the median prescription dose of 120 Gy (range, 100-140 Gy). The median seed number was 80 (range 10-214). Clinical efficacy was evaluated with Response Evaluation Criteria in Solid Tumors. FINDINGS: Fifteen patients were selected, eleven of whom had papillary carcinoma, two suffered from follicular carcinoma, and two were diagnosed with medullary carcinoma. These patients had twenty-four nodes in total. After they received salvage surgery and/or radioactive iodine (RAI) therapy, local recurrence was detected in all of them. No less than one node was observed in everyone's cervical or supraclavicular areas, and four patients had lung metastatic. The median follow-up period lasted 48 months (range, 5-93 months). All patients did not develop locoregional recurrence after experiencing 125I seed brachytherapy. Only three of them formed new metastases in nontarget regional nodes after brachytherapy, and additional brachytherapy can solve all regional failure problems. No significant adverse events were observed in any patient. IMPLICATIONS: For the chosen patients, 125I seed brachytherapy is feasible for treating refractory local recurrence from non-anaplastic thyroid cancer. Further studies are required to determine the role of 125I seed brachytherapy in the treatment of thyroid cancer.

Dominant role of DNA methylation over H3K9me3 for IAP silencing in endoderm.

Silencing of endogenous retroviruses (ERVs) is largely mediated by repressive chromatin modifications H3K9me3 and DNA methylation. On ERVs, these modifications are mainly deposited by the histone methyltransferase Setdb1 and by the maintenance DNA methyltransferase Dnmt1. Knock-out of either Setdb1 or Dnmt1 leads to ERV de-repression in various cell types. However, it is currently not known if H3K9me3 and DNA methylation depend on each other for ERV silencing. Here we show that conditional knock-out of Setdb1 in mouse embryonic endoderm results in ERV de-repression in visceral endoderm (VE) descendants and does not occur in definitive endoderm (DE). Deletion of Setdb1 in VE progenitors results in loss of H3K9me3 and reduced DNA methylation of Intracisternal A-particle (IAP) elements, consistent with up-regulation of this ERV family. In DE, loss of Setdb1 does not affect H3K9me3 nor DNA methylation, suggesting Setdb1-independent pathways for maintaining these modifications. Importantly, Dnmt1 knock-out results in IAP de-repression in both visceral and definitive endoderm cells, while H3K9me3 is unaltered. Thus, our data suggest a dominant role of DNA methylation over H3K9me3 for IAP silencing in endoderm cells. Our findings suggest that Setdb1-meditated H3K9me3 is not sufficient for IAP silencing, but rather critical for maintaining high DNA methylation.