Impact of Imine Bond Orientations and Acceptor Groups on Photocatalytic Hydrogen Generation of Donor-Acceptor Covalent Organic Frameworks.

Covalent organic frameworks (COFs) have emerged as one of the most studied photocatalysts owing to their adjustable structure and bandgaps. However, there is limited research on regulating the light-harvesting capabilities of acceptor building blocks in donor-acceptor (D-A) isomer COFs with different bond orientations. This investigation is crucial for elucidating the structure-property-performance relationship of COF photocatalysts. Herein, a series of D-A isostructural COFs are synthesized with different imine bond orientations using benzothiadiazole and its derivatives-based organic building units. Extended light absorption is achieved in COFs with acceptor groups that have strong electron-withdrawing capacities, although this resulted a decreased hydrogen generation efficiency. Photocatalytic experiments indicated that dialdehyde benzothiadiazole-based COFs, HIAM-0015, exhibit the highest hydrogen generation rate (17.99 mmol g-1 h-1), which is 15 times higher than its isomer. The excellent photocatalytic performance of HIAM-0015 can be attributed to its fast charge separation and migration. This work provides insights into the rational design and synthesis of D-A COFs to achieve efficient photocatalytic activity.

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.

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.

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 .

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.

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.

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.

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.

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.

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.

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.

3D-Printed Template-Guided 125I Seed Brachytherapy: A Salvage Approach for Locoregional Refractory Recurrence of Papillary Thyroid Cancer.

BACKGROUND: Papillary thyroid carcinoma (PTC) is typically treated with surgical resection, even in recurrent cases. However, some cases of recurrent PTC are refractory to the conventionally used locoregional radiotherapy and resection methods. 125I seed permanent brachytherapy has emerged as a promising alternative for such PTCs, but no effective brachytherapy protocol has been reported for tumors with a huge volume, liquefaction, necrosis, and skin invasion. CASE PRESENTATION: A 47-year-old man presented with recurrence 8 years after 2 thyroidectomy procedures for PTC and recurrent PTC. The tumor measured 6 × 7 × 8 cm3 and exhibited liquefaction, necrosis, and skin invasion. The patient was treated at our hospital from December 2017 to November 2018. He received one round of 125I seed temporary brachytherapy and 4 rounds of 125I seed permanent implantation. The activity of the seeds was 0.3-3.0 mCi, and the total dose delivered to the tumor was 145 Gy. The recurrent tumor was successfully removed by 125I seed brachytherapy guided with a 3D-printed template and ultrasound and CT scanning. The refractory tumor healed uneventfully after 125I seed brachytherapy without recurrence over the 25-month follow-up. CONCLUSIONS: To the best of our knowledge, this is the first reported case of a large thyroid carcinoma that was effectively treated by 3D-printed template-guided 125I seed brachytherapy.

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.

Robust and Swiftly Reversible Thermochromic Behavior of a 2D Perovskite of (C6H4(CH2NH3)2)(CH3NH3)[Pb2I7] for Smart Window and Photovoltaic Smart Window Applications.

Highly robust, swiftly reversible thermochromic nature of a two-dimensional (2D) perovskite of (PDMA)(CH3NH3)n-1PbnI3n+1, nominally prepared as n = 2 is found, where PDMA = C6H4(CH2NH3)2. A wide band gap variation from 700 to 430 nm is observed between room temperature and >60 °C under ambient conditions, resulting from moisture absorption and desorption. X-ray diffraction and Fourier-transform infrared spectroscopy are performed to analyze the hydrated and dehydrated states. Furthermore, the (PDMA)(CH3NH3)n-1PbnI3n+1 film is demonstrated as an active material for smart windows and thermochromic solar cells, which could lower the inside air temperature in an enclosed space and supply a power conversion efficiency of more than 0.5% at a high ambient temperature, respectively. Overall, we may pave a pathway for exploring the novel phenomena and applications of Dion-Jacobson 2D perovskites.

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.

125I brachytherapy seeds implantation for an inoperable large retroperitoneal leiomyosarcoma.

Retroperitoneal leiomyosarcoma is relatively uncommon. Leiomyosarcoma has accounted for about 5%-10% of soft-tissue sarcoma, and 1/2-2/3 of the primary lesions were retroperitoneal, with a cumulative 5-year survival rate of only 35%.Leiomyosarcoma is one kind of soft-tissue sarcoma with the lowest survival rates due to the invasive growth, difficult treatment, and poor prognosis.The present study reported a case of a 78-year-old male diagnosed as left retroperitoneal leiomyosarcoma, who had received three operations. Computed tomography (CT) demonstrated a mass of approximately 12.9 cm × 6.9 cm × 6.6 cm in his retroperitoneal region. The Eastern cooperative oncology group and numerical rating scale scores of pain were 1 and 5, respectively. Multiple treatment strategies were administered, including the application of drainage and125I seed implantation. A total of 90125I seeds were implanted into the tumor through repetitious operations, with 30 seeds each time. Treatment planning system was involved to calculate the source distribution.125I seeds with the activity of 0.5 mCi were implanted under the guidance of CT, and dosimetric verification was performed after the operation. D90 (90% minimum prescription dose received by target volume) was 40 Gy. Follow-up was performed after 6 months, and complete response was achieved in the local lesions. However, there was no evidence-based treatment currently and the majority of our knowledge was based on results from case reports, thus further studies would be required.

The failure of DAC to induce OCT2 expression and its remission by hemoglobin-based nanocarriers under hypoxia in renal cell carcinoma.

Background: Human organic cation transporter 2 (OCT2) is the most abundant and important uptake transporter involved in the renal excretion of cationic drugs. Abnormal hypermethylation- mediated silencing of OCT2 results in oxaliplatin resistance in renal cell carcinoma (RCC). The epigenetic activation of OCT2 by decitabine (DAC) reversed this resistance in normoxic conditions. Given the hypoxic characteristic of RCC, it is still unclear whether hypoxia promotes DAC resistance and is involved in the regulation of OCT2. Methods: The mRNA and protein expression of OCT2 was determined by qRT-PCR and Western blotting. MSRE-qPCR and BSP were used to examine methylation modifications at the OCT2 promoter. The ChIP-qPCR analysis was performed to detect the abundance of histone modification and HIF-1α. The accumulation of DAC and 5-mC were detected using LC-MS, and the amount of 5-hmC was determined by dot blot analysis. To understand the role of hypoxia in the regulation of equilibrative nucleoside transporter 1 (ENT1) expression, the HIF-1α KO cell model was constructed. The re-emulsion method was used for the construction of H-NPs, an oxygen nanocarrier based on hemoglobin, to alleviate the drug resistance of DAC under hypoxia. Results: DAC was unable to upregulate OCT2 expression in hypoxic conditions because of the hypermethylation and low H3K4me3 modification in its promoter region. Hypoxia-mediated repression of human ENT1, which was markedly suppressed in RCC, resulted in a decrease in the cellular accumulation of DAC. Besides, hypoxia-induced upregulation of histone deacetylase HDAC9, which impaired the enrichment of H3K27ac modification in the OCT2 promoter, led to the transcriptional repression of OCT2. H-NPs could attenuate the hypoxia-induced loss of DAC activity and sensitize RCC cells to the sequential combination therapy of DAC and oxaliplatin. Conclusions: Hypoxia-mediated repression of ENT1 led to the inability of DAC to upregulate the expression of OCT2 under hypoxia. H-NPs could alleviate resistance to oxaliplatin and DAC in RCC cells under hypoxia and may have potential clinical applications.

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.

p53 protein expression affected by TP53 polymorphism is associated with the biological behavior and prognosis of low rectal cancer.

Low rectal cancer is a subtype of colorectal cancer at a special anatomic site with distinct biological behavior. TP53 is one of the most important cancer suppressor genes, and its structural variation and abnormal expression has been revealed to be associated with multiple cancer types. However, to the best of our knowledge, the association of p53 protein expression with its gene polymorphism, biological behavior and prognosis in low rectal cancer has not been clarified. Therefore, the current study aimed to explore these associations. In the present study, 347 patients with low rectal cancer and 353 controls were enrolled. Kompetitive Allele-Specific Polymerase Chain Reaction was used to detect five polymorphic sites of the TP53 gene (rs1042522, rs12947788, rs1625895, rs2909430 and rs12951053), while immunohistochemistry was used to detect the protein expression of TP53. The associations between p53 protein expression and TP53 polymorphism, biological behavior and prognosis in low rectal cancer were systematically analyzed. In low rectal cancer, p53 protein expression was markedly higher in TP53 rs1042522 mutant carriers compared with that in other genotypes where expression was higher in poorly differentiated, III-IV phase and T3-4 phase tumors, and in III-IV phase female patients. The survival time of patients with low p53 protein expression was evidently longer in females, non-smokers and patients >60 years old. In summary, p53 protein expression was identified to be affected by TP53 rs1042522 polymorphism, and was associated with the biological behavior and prognosis of low rectal cancer. TP53 rs1042522 and the associated protein expression could be used as indicators for biological behavior and prognosis in low rectal cancer.