Enhanced Sampling Molecular Dynamics Simulations Reveal Transport Mechanism of Glycoconjugate Drugs through GLUT1.

Glucose transporters GLUT1 belong to the major facilitator superfamily and are essential to human glucose uptake. The overexpression of GLUT1 in tumor cells designates it as a pivotal target for glycoconjugate anticancer drugs. However, the interaction mechanism of glycoconjugate drugs with GLUT1 remains largely unknown. Here, we employed all-atom molecular dynamics simulations, coupled to steered and umbrella sampling techniques, to examine the thermodynamics governing the transport of glucose and two glycoconjugate drugs (i.e., 6-D-glucose-conjugated methane sulfonate and 6-D-glucose chlorambucil) by GLUT1. We characterized the specific interactions between GLUT1 and substrates at different transport stages, including substrate recognition, transport, and releasing, and identified the key residues involved in these procedures. Importantly, our results described, for the first time, the free energy profiles of GLUT1-transporting glycoconjugate drugs, and demonstrated that H160 and W388 served as important gates to regulate their transport via GLUT1. These findings provide novel atomic-scale insights for understanding the transport mechanism of GLUT1, facilitating the discovery and rational design of GLUT1-targeted anticancer drugs.

Effects of chemically-reductive trace gas contaminants on non-thermal plasma inactivation of an airborne virus.

Transmission of airborne infectious diseases poses great risk for public health and socio-economic stability, thus, there is a need for an effective control method targeting the spread and transmission of pathogenic aerosols. The existence of chemically-reductive trace air contaminants in animal agriculture may affect the oxidation inactivation process of pathogens. In this study, we report how the presence of such gasses impacts the effectiveness of using non-thermal plasma (NTP) within a packed-bed dielectric barrier discharge reactor to inactivate MS2 bacteriophage. Inactivation of the aerosolized bacteriophage is determined by the combination of viability and polymerase chain reaction assays. Using a plasma power source with a voltage of 20 kV and frequency of 350 Hz, after differentiating and excluding the physical removal effects of viral aerosols potentially caused by plasma, the baseline inactivation of MS2 aerosol in air has been determined based on an overall air flow rate of 200 Liters per minute and plasma discharge power of 1.8 W. When either ammonia or hydrogen sulfide gas is introduced into the airstream at a concentration of 1 part per million, the NTP virus inactivation efficiency is reduced to around 0.5-log from the 1-log baseline inactivation in air alone. Higher concentrations of those gasses will not further inhibit the effectiveness of plasma inactivation.

Preoperatively predicting vessels encapsulating tumor clusters in hepatocellular carcinoma: Machine learning model based on contrast-enhanced computed tomography.

BACKGROUND: Recently, vessels encapsulating tumor clusters (VETC) was considered as a distinct pattern of tumor vascularization which can primarily facilitate the entry of the whole tumor cluster into the bloodstream in an invasion independent manner, and was regarded as an independent risk factor for poor prognosis in hepatocellular carcinoma (HCC). AIM: To develop and validate a preoperative nomogram using contrast-enhanced computed tomography (CECT) to predict the presence of VETC+ in HCC. METHODS: We retrospectively evaluated 190 patients with pathologically confirmed HCC who underwent CECT scanning and immunochemical staining for cluster of differentiation 34 at two medical centers. Radiomics analysis was conducted on intratumoral and peritumoral regions in the portal vein phase. Radiomics features, essential for identifying VETC+ HCC, were extracted and utilized to develop a radiomics model using machine learning algorithms in the training set. The model's performance was validated on two separate test sets. Receiver operating characteristic (ROC) analysis was employed to compare the identified performance of three models in predicting the VETC status of HCC on both training and test sets. The most predictive model was then used to constructed a radiomics nomogram that integrated the independent clinical-radiological features. ROC and decision curve analysis were used to assess the performance characteristics of the clinical-radiological features, the radiomics features and the radiomics nomogram. RESULTS: The study included 190 individuals from two independent centers, with the majority being male (81%) and a median age of 57 years (interquartile range: 51-66). The area under the curve (AUC) for the combined radiomics features selected from the intratumoral and peritumoral areas were 0.825, 0.788, and 0.680 in the training set and the two test sets. A total of 13 features were selected to construct the Rad-score. The nomogram, combining clinical-radiological and combined radiomics features could accurately predict VETC+ in all three sets, with AUC values of 0.859, 0.848 and 0.757. Decision curve analysis revealed that the radiomics nomogram was more clinically useful than both the clinical-radiological feature and the combined radiomics models. CONCLUSION: This study demonstrates the potential utility of a CECT-based radiomics nomogram, incorporating clinical-radiological features and combined radiomics features, in the identification of VETC+ HCC.

Upregulation of Wheat Heat Shock Transcription Factor TaHsfC3-4 by ABA Contributes to Drought Tolerance.

Drought stress can seriously affect the yield and quality of wheat (Triticum aestivum). So far, although few wheat heat shock transcription factors (Hsfs) have been found to be involved in the stress response, the biological functions of them, especially the members of the HsfC (heat shock transcription factor C) subclass, remain largely unknown. Here, we identified a class C encoding gene, TaHsfC3-4, based on our previous omics data and analyzed its biological function in transgenic plants. TaHsfC3-4 encodes a protein containing 274 amino acids and shows the basic characteristics of the HsfC class. Gene expression profiles revealed that TaHsfC3-4 was constitutively expressed in many tissues of wheat and was induced during seed maturation. TaHsfC3-4 could be upregulated by PEG and abscisic acid (ABA), suggesting that this Hsf may be involved in the regulation pathway depending on ABA in drought resistance. Further results represented that TaHsfC3-4 was localized in the nucleus but had no transcriptional activation activity. Notably, overexpression of TaHsfC3-4 in Arabidopsis thaliana pyr1pyl1pyl2pyl4 (pyr1pyl124) quadruple mutant plants complemented the ABA-hyposensitive phenotypes of the quadruple mutant including cotyledon greening, root elongation, seedling growth, and increased tolerance to drought, indicating positive roles of TaHsfC3-4 in the ABA signaling pathway and drought tolerance. Furthermore, we identified TaHsfA2-11 as a TaHsfC3-4-interacting protein by yeast two-hybrid (Y2H) screening. The experimental data show that TaHsfC3-4 can indeed interact with TaHsfA2-11 in vitro and in vivo. Moreover, transgenic Arabidopsis TaHsfA2-11 overexpression lines exhibited enhanced drought tolerance, too. In summary, our study confirmed the role of TaHsfC3-4 in response to drought stress and provided a target locus for marker-assisted selection breeding to improve drought tolerance in wheat.

Identification and validation of PCSK9 as a prognostic and immune-related influencing factor in tumorigenesis: a pan-cancer analysis.

Introduction: Proprotein convertase subtilisin/kexin-9 (PCSK9) has been primarily studied in the cardiovascular field however, its role in cancer pathophysiology remains incompletely defined. Recently, a pivotal role for PCSK9 in cancer immunotherapy was proposed based on the finding that PCSK9 inhibition was associated with enhancing the antigen presentation efficacy of target programmed cell death-1 (PD-1). Herein, we provide results of a comprehensive pan-cancer analysis of PCSK9 that assessed its prognostic and immunological functions in cancer. Methods: Using a variety of available online cancer-related databases including TIMER, cBioPortal, and GEPIA, we identified the abnormal expression of PCSK9 and its potential clinical associations in diverse cancer types including liver, brain and lung. We also validated its role in progression-free survival (PFS) and immune infiltration in neuroblastoma. Results: Overall, the pan-cancer survival analysis revealed an association between dysregulated PCSK9 and poor clinical outcomes in various cancer types. Specifically, PCSK9 was extensively genetically altered across most cancer types and was consistently found in different tumor types and substages when compared with adjacent normal tissues. Thus, aberrant DNA methylation may be responsible for PCSK9 expression in many cancer types. Focusing on liver hepatocellular carcinoma (LIHC), we found that PCSK9 expression correlated with clinicopathological characteristics following stratified prognostic analyses. PCSK9 expression was significantly associated with immune infiltrate since specific markers of CD8+ T cells, macrophage polarization, and exhausted T cells exhibited different PCSK9-related immune infiltration patterns in LIHC and lung squamous cell carcinoma. In addition, PCSK9 was connected with resistance of drugs such as erlotinib and docetaxel. Finally, we validated PCSK9 expression in clinical neuroblastoma samples and concluded that PCSK9 appeared to correlate with a poor PFS and natural killer cell infiltration in neuroblastoma patients. Conclusion: PCSK9 could serve as a robust prognostic pan-cancer biomarker given its correlation with immune infiltrates in different cancer types, thus potentially highlighting a new direction for targeted clinical therapy of cancers.

Development and validation of prediction models for the prognosis of colon cancer with lung metastases: a population-based cohort study.

Background: Current studies on the establishment of prognostic models for colon cancer with lung metastasis (CCLM) were lacking. This study aimed to construct and validate prediction models of overall survival (OS) and cancer-specific survival (CSS) probability in CCLM patients. Method: Data on 1,284 patients with CCLM were collected from the Surveillance, Epidemiology, and End Results (SEER) database. Patients were randomly assigned with 7:3 (stratified by survival time) to a development set and a validation set on the basis of computer-calculated random numbers. After screening the predictors by the least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression, the suitable predictors were entered into Cox proportional hazard models to build prediction models. Calibration curves, concordance index (C-index), time-dependent receiver operating characteristic (ROC) curves, and decision curve analysis (DCA) were used to perform the validation of models. Based on model-predicted risk scores, patients were divided into low-risk and high-risk groups. The Kaplan-Meier (K-M) plots and log-rank test were applied to perform survival analysis between the two groups. Results: Building upon the LASSO and multivariate Cox regression, six variables were significantly associated with OS and CSS (i.e., tumor grade, AJCC T stage, AJCC N stage, chemotherapy, CEA, liver metastasis). In development, validation, and expanded testing sets, AUCs and C-indexes of the OS and CSS prediction models were all greater than or near 0.7, which indicated excellent predictability of models. On the whole, the calibration curves coincided with the diagonal in two models. DCA indicated that the models had higher clinical benefit than any single risk factor. Survival analysis results showed that the prognosis was worse in the high-risk group than in the low-risk group, which suggested that the models had significant discrimination for patients with different prognoses. Conclusion: After verification, our prediction models of CCLM are reliable and can predict the OS and CSS of CCLM patients in the next 1, 3, and 5 years, providing valuable guidance for clinical prognosis estimation and individualized administration of patients with CCLM.

Time-Series Transcriptome Analysis Reveals the Molecular Mechanism of Ethylene Reducing Cold Sensitivity of Postharvest 'Huangguan' Pear.

'Huangguan' pear (Pyrus bretschneideri Rehd) fruit is susceptible to cold, characterized by developing peel browning spots (PBS) during cold storage. Additionally, ethylene pretreatment reduces chilling injury (CI) and inhibits PBS occurrence, but the mechanism of CI remains unclear. Here, we deciphered the dynamic transcriptional changes during the PBS occurrence with and without ethylene pretreatment via time-series transcriptome. We found that ethylene suppressed the cold-signaling gene expression, thereby decreasing the cold sensitivity of the 'Huangguan' fruit. Moreover, the "Yellow" module closely correlated with PBS occurrence was identified via weighted gene co-expression network analysis (WGCNA), and this module was related to plant defense via Gene Ontology (GO) enrichment analysis. Local motif enrichment analysis suggested that the "Yellow" module genes were regulated by ERF and WRKY transcription factors. Functional studies demonstrated that PbWRKY31 has a conserved WRKY domain, lacks transactivation activity, and localizes in the nucleus. PbWRKY31-overexpressed Arabidopsis were hypersensitive to cold, with higher expression levels of cold signaling and defense genes, suggesting that PbWRKY31 participates in regulating plant cold sensitivity. Collectively, our findings provide a comprehensive transcriptional overview of PBS occurrence and elucidate the molecular mechanism by which ethylene reduces the cold sensitivity of 'Huangguan' fruit as well as the potential role of PbWRKY31 in this process.

Thermal Degradation Characteristics of Styrene-Butadiene-Styrene Copolymer Asphalt Binder Filled with an Inorganic Flame-Retarding Agent.

Asphalt binder is a complex mixture of dark brown polymers composed of hydrocarbons with generally poor fire resistance. To improve its flame retardancy when used in tunnel asphalt pavements, a new inorganic flame-retardant filler (FR) containing magnesium hydroxide, aluminum hydroxide, inorganic phosphate, and melamine salt was explored. Thereafter, limiting oxygen index (LOI) and smoke suppression tests for the flame-retarded asphalt binder (FRA) mastics mixed with FR and styrene-butadiene-styrene (SBS) copolymer asphalt binder were conducted. Thermogravimetric (TG) and differential scanning calorimetry (DSC) curves for the FRA were correspondingly generated. Based on the TG data, the reaction function g(α), apparent activation energy Ea, and pre-exponential factor A were quantitatively evaluated using kinetic analysis. In addition, a Fourier transform infrared spectrometry (FTIR) test was utilized to assess the effects of the presence of FR on the chemical composition of the asphalt binder. Dynamic shear rheometer (DSR) tests were also performed to evaluate the rheological behavior of FRA. Results show that the presence of the FR significantly reduced the LOI and improved the smoke suppression during combustion of the asphalt binder mastics. The presence of FR was found to increase the Ea and the complexity of the combustion reaction, thereby improving the flame retardancy of the asphalt binder. FTIR analysis indicated that the presence of FR did not induce any strong chemical reactions to significantly impact or alter the functional groups of the asphalt binder. Furthermore, it was also observed that the rutting parameter and critical failure temperature of FRA increased with the addition of FR due to the stiffening effect of the solid FR particles.

Integrated multi-omics analysis identifies ENY2 as a predictor of recurrence and a regulator of telomere maintenance in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and has a high recurrence rate. Accurate prediction of recurrence risk is urgently required for tailoring personalized treatment programs for individual HCC patients in advance. In this study, we analyzed a gene expression dataset from an HCC cohort with 247 samples and identified five genes including ENY2, GPAA1, NDUFA4L2, NEDD9, and NRP1 as the variables for the prediction of HCC recurrence, especially the early recurrence. The Cox model and risks score were validated in two public HCC cohorts (GSE76427 and The Cancer Genome Atlas (TCGA)) and one cohort from Huashan Hospital, which included a total of 641 samples. Moreover, the multivariate Cox regression analysis revealed that the risk score could serve as an independent prognostic factor in the prediction of HCC recurrence. In addition, we found that ENY2, GPAA1, and NDUFA4L2 were significantly upregulated in HCC of the two validation cohorts, and ENY2 had significantly higher expression levels than another four genes in malignant cells, suggesting that ENY2 might play key roles in malignant cells. The cell line analysis revealed that ENY2 could promote cell cycle progression, cell proliferation, migration, and invasion. The functional analysis of the genes correlated with ENY2 revealed that ENY2 might be involved in telomere maintenance, one of the fundamental hallmarks of cancer. In conclusion, our data indicate that ENY2 may regulate the malignant phenotypes of HCC via activating telomere maintenance.

Effects of Tumor-Derived DNA on CXCL12-CXCR4 and CCL21-CCR7 Axes of Hepatocellular Carcinoma Cells and the Regulation of Sinomenine Hydrochloride.

Currently, chemokines and their receptors, CXCL12-CXCR4 and CCL21-CCR7 axes, are deemed vital factors in the modulation of angiogenesis and are crucial for the growth and development of liver cancer. Tumor-derived DNA can be recognized by immune cells to induce an autoimmune response. In this study, we demonstrated the mechanism of tumor-derived DNA on the CXCL12-CXCR4 and CCL21-CCR7 axes of hepatocellular carcinoma (HCC) cells and the regulatory effect of sinomenine hydrochloride. Tumor-derived DNA was separated from HCCLM cell lines. Tumor-derived DNA was transfected into SK-Hep1 cells by Lipofectamine 2000. We found that sinomenine hydrochloride reduced the expression of CXCR4, CXCR12, CCR7, and CCL21 in HCC cells, suppressed the growth and invasion of HCC cells, and increased apoptosis. In contrast to the controls, the protein expressions of CXCR4, CXCL12, CCR7, CCL21, P-ERK1/2, MMP-9, and MMP-2 in SK-Hep1 cells were significantly increased after transfection of tumor-derived DNA, while the increase was reversed by sinobine hydrochloride. Acid sinomenine interferes with tumor-derived DNA and affects ERK/MMP signaling via the CXCL12/CXCR4 axis in HCC cells. CXCR4 siRNA and CCR7 siRNA attenuated tumor-derived DNA activation of ERK1/2/MMP2/9 signaling pathways in HCC cells. CXCR4-oe and CCR7-OE enhance the stimulation of erK1/2/MMP2/9 signaling pathway by tumor-derived DNA in HCC cells. Tumor-derived DNA reduced apoptosis and increased invasion of SK-Hep1 cells by CXCL12-CXCR4 axis and CCL21-CCR7 axis, and sinobine hydrochloride reversed this regulation. These results strongly suggest that tumor-derived DNA can increase the growth and invasion of oncocytes via the upregulation of the expression of CXCL12-CXCR4 and CCL21-CCR7 axis and through ERK1/2/MMP2/9 signaling pathway in HCC cells, and sinobine hydrochloride can inhibit this signaling pathway, thus inhibiting HCC cells. These results provide new potential therapeutic targets for blocking the progression of HCC induced by CXCL12-CXCR4 axis and CCL21-CCR7.

Corrigendum: The Visual Acuity Outcome and Relevant Factors Affecting Visual Improvement in Pediatric Sporadic Chiasmatic-Hypothalamic Glioma Patients Who Received Surgery.

[This corrects the article DOI: 10.3389/fneur.2020.00766.].

Epidemiological characteristics of central nervous system tumors in children: a 5-year review of 3180 cases from Beijing Tiantan Hospital.

BACKGROUND: To describe the epidemiological characteristics of central nervous system (CNS) tumors in children, based on the neurosurgery department of Beijing Tiantan Hospital. METHODS: From January 2015 to December 2019, 3180 children were histopathologically diagnosed with CNS tumors based on the 2016 World Health Organization (WHO) classification of tumors. Patients were 0 to 15 years old. We analyzed age-related gender preferences, tumor locations, and the histological grades of the tumors. In addition, the epidemiological characteristics of the five most common intracranial tumors were compared to the previous studies. RESULTS: In this study, intracranial and spinal tumors account for 96.4% (3066) and 3.6% (114) of all tumors, with a preponderance of supratentorial tumors (57.9%). Among all pediatric patients, low-grade tumors comprise 67.1% (2 135). The integral gender ratio of males to females is 1.47: 1 and the average age of patients is 7.59 years old. The five most common intracranial tumors are craniopharyngioma (15.4%), medulloblastoma (14.3%), pilocytic astrocytoma (11.8%), diffuse astrocytoma (9.8%), and anaplastic ependymoma (4.8%). CONCLUSIONS: Due to the lack of national data on childhood brain tumors, we used a large nationally representative population sample based on the largest pediatric neurosurgery center in China. We analyzed the data of the past 5 years, reflecting the incidence of CNS tumors in Chinese children to a certain extent, and laying a data foundation for subsequent clinical studies.

The role of imaging features and resection status in the survival outcome of sporadic optic pathway glioma children receiving different adjuvant treatments.

Optic pathway glioma (OPG) is a rare brain tumor affecting children, with no standard treatment strategy. This study described the sporadic OPG survival outcomes after surgical treatment and analyzed the role of imaging features and resection status in children receiving different adjuvant treatments. This retrospective study included 165 OPG patients whose clinical information were obtained from the hospital record system. Tumor volume and residual tumor volume were calculated by delineating the lesion area. Kaplan-Meier method and Cox proportional hazards model were conducted to analyze the independent prognosis factor. A total of 165 patients were included in this study. Respectively, the 5-year overall survival (OS) and progression-free survival (PFS) were 87.58% and 77.87%. Residual tumor size and first adjuvant treatment (AT) after surgery were both associated with PFS. In patients with small-size residual tumors, there was no significant difference in PFS between the AT treatment groups. Moreover, age, exophytic cystic components, leptomeningeal metastases, and AT were associated with OS. In patients with exophytic cystic components and those with leptomeningeal metastases, there was no significant difference in OS. Our results revealed that OPG patients could avoid or defer AT by maximized resection. Age ≤ 2 years was a disadvantageous factor for OS. Patients with exophytic cystic components were more likely to benefit from primary surgery, and CT or RT was not beneficial for these patients. Patients with leptomeningeal metastases had a poor prognosis regardless of the treatment they received. Future prospective clinical studies are needed to develop more effective treatment regimens.

Resveratrol Alleviates Hepatic Fibrosis in Associated with Decreased Endoplasmic Reticulum Stress-Mediated Apoptosis and Inflammation.

Hepatic fibrosis (HF) is the typical response to chronic liver disease and is characterized by deposition of abundant extracellular matrix. The aim of the present study was to investigate the protective effect of resveratrol (RSV) in a CCl4-induced rat model of HF. We demonstrate that the administration of RSV effectively improves liver function and ameliorates liver fibrosis by reducing collagen deposition and reversing the expression of COL1A1 and PPAR-γ. Treatment efficacy of RSV could be attributed to reversed epithelial-mesenchymal transition progress with upregulated expression of E-cadherin and downregulated N-cadherin, vimentin, and α-SMA. Moreover, RSV significantly decreased the levels of endoplasmic reticulum stress (ERS)-related proteins CHOP; Bip; cleaved caspase-3, caspase-7, and caspase-12; Bax; and Bak while promotes the expression of anti-apoptosis protein Bcl2. The important role of ERS in HF was confirmed by using 4-PBA, an ERS inhibitor, which markedly ameliorated CCl4-induced HF. Further, mechanistic studies demonstrated that RSV significantly decreased CCl4-induced transforming growth factor-ß synthesis and inflammatory factor (tumor necrosis factor-α and interleukin-6) expression and reduced the inflammation of hepatic stellate cells by inhibiting the NF-κB pathway in vivo and in vitro. In conclusion, the results suggested that RSV ameliorated HF in associated with decreased ERS-induced apoptosis and inflammation in rats.

Contact and Tribological Study of Micro/Nano Groove Texture on the Surface of Gas Bearing Materials Based on Nanoscale.

As a kind of sliding bearing, the gas bearing is widely used in high-speed rotating machinery. It realizes energy cleaning in the field of high-speed rotating machinery. In order to solve the problem of reducing the service life of gas bearings due to friction during startup and shutdown, we use micromachining technology to process groove textures with different groove widths on the surface of 0Cr17Ni7Al, a common material for gas bearings. A ball-disc friction contrast test is conducted under dry friction conditions with and without texture. The experiment shows that the lowest average friction coefficient of 0.8 mm texture is σ = 0.745. When the friction radius is 22.5 mm, the wear rate of 1.0 mm texture is the lowest at ω = 3.118 × 10-4mm3/N·mm. However, the maximum friction coefficient reached is σ = 0.898. Under the nanometer scale, the contact between friction pairs is fully analyzed. The influence mechanism of different groove widths, friction impacts and climbing heights on the friction and wear properties of the micromechanical groove texture on the surface of 0Cr17Ni7Al stainless steel is studied at the nano-fractal scale. The effects of different width grooves on the surface texture and tribological properties of the micromachine are studied.

LncRNA GASAL1 promotes hepatocellular carcinoma progression by up-regulating USP10-stabilized PCNA.

Hepatocellular carcinoma (HCC) is a fatal malignancy which has insufficient treatment options. Long non-coding RNA (lncRNA) GASAL1 was discovered to be conspicuously up-regulated in HCC. However, the study on the role of GASAL1 in HCC reamins limited. Our study aimed at exploring the role and mechanism of GASAL1 in HCC. RT-qPCR or Western blot was conducted to examine the expression of RNAs or proteins. Functional assays were carried out to investigate the impact of GASAL1, USP10, and PCNA on HCC cells. Mechanism assays were performed to fathom out the relationship among GASAL1, miR-193b-5p, USP10, and PCNA. In vivo assays were also employed to determine the role of GASAL1 in HCC tumor growth and metastases. According to the data collected, GASAL1 displayed a high expression in HCC cells and GASAL1 knockdown led to impeded cell proliferation and migration, as well as tumor progression. A series of mechanism analysis demonstrated GASAL1 could sponge miR-193b-5p to raise the expression of USP10. Moreover, USP10 could induce PCNA deubiquitination to promote HCC cell growth. To conclude, GASAL1 plays an oncogenic role in HCC. GASAL1 could up-regulate USP10 via competitively binding to miR-193b-5p. And USP10 could strengthen cell proliferative and migratory abilities through deubiquitinating PCNA.

Temperature-compensated optical fiber sensor for volatile organic compound gas detection based on cholesteric liquid crystal.

External temperature variations inevitably affect the accuracy of a liquid crystal sensor. Therefore, we propose a novel temperature-compensated fiber volatile organic compound (VOC, using acetone as a model compound) gas sensor. The proposed sensor consists of a short segment of hollow-core fiber (HCF), which is spliced on a multimode fiber. Cholesteric liquid crystal (CLC) is sealed into HCF to sense the temperature, and another type of CLC is coated on the end face of HCF for VOC gas detection. The VOC gas concentration and ambient temperature can be simultaneously measured by monitoring the wavelength shifts of two Bragg reflection peaks caused by two types of CLCs. The effects of the CLC thickness on the sensitivities of temperature and acetone concentration are investigated, and optimal parameters are chosen. An optimal sensor can reach a temperature sensitivity of 2.53 nm/°C and acetone concentration sensitivity of 48.46 nm·L/mmol at 8-44°C. In addition, temperature compensation capability, repeatability, response time, and stability are also researched. The experimental results prove this sensor has great application potential in high-precision real-time VOC gas monitoring and detection.

Development of a predictive nomogram for early recurrence of hepatocellular carcinoma in patients undergoing liver transplantation.

BACKGROUND: An individual prognostic model that includes inflammation caused by the delayed recovery of liver function after surgery for the early recurrence of hepatocellular carcinoma (HCC) following liver transplantation (LT) has not been well determined. Our aim was to develop a nomogram model for predicting individual survival and early recurrence following LT for patients. METHODS: Retrospective data, including clinical pathology and follow-up data, on HCC patients were collected between October 2016 and October 2019 at Huashan Hospital Affiliated to Fudan University. A nomogram estimating recurrence post-transplantation was constructed using multivariate Cox regression analysis. RESULTS: A total of 210 patients were included in the present study. The multivariate estimators of recurrence consisted of age, maximum tumor diameter, tumor thrombus, microvascular invasion (MVI), alanine aminotransferase and alpha-fetoprotein on postoperative day 7. Nomogram of recurrence-free survival was developed. The calibration and discrimination of the novel model were assessed with the calibration curves and concordance index (C-index). Its reliability and advantages were evaluated by comparing it with the conventional American Joint Committee on Cancer (AJCC) 8th edition staging system using integrated discrimination improvement (IDI) and net reclassification improvement (NRI). In comparison to the AJCC 8th edition staging system, the C-index (development set: 0.796 vs. 0.643, validation set: 0.741 vs. 0.563), the area under the receiver operating characteristic curve (AUC) of the validation set (1-year AUC: 0.732 vs. 0.586, 2-year AUC: 0.705 vs. 0.504), the development set (1-year AUC: 0.799 vs. 0.551, 2-year AUC: 0.801 vs. 0.512), and this model's calibration plots all showed improved performance. In addition, NRI and IDI verified that the nomogram is an accurate prognostic tool. Subsequently, a web calculator was generated to assess the risk of tumor recurrence post-LT. CONCLUSIONS: The nomogram, based on clinical and pathological factors, showed good accuracy in estimating prognostic recurrence and can be used to guide individual patient follow-up and treatment.

Severity of early allograft dysfunction following donation after circulatory death liver transplantation: a multicentre study.

BACKGROUND: Early allograft dysfunction (EAD) is associated with decreased graft and patient survival rates. This study aimed to identify the severity of EAD and develop a predictive model for EAD after donation after circulatory death (DCD) liver transplantation (LT). Furthermore, the influence of operative time on EAD incidence was also evaluated. METHODS: In this retrospective, multicentre cohort study, nomograms were established based on a single-centre training cohort (n=321) and validated in a 3-center validation cohort (n=501). RESULTS: The incidence rate of EAD was 46.4% (149/321) in the training cohort and 40.5% (203/501) in the validation cohort. Of the 149 EAD patients in the training cohort, 77 patients with either elevated alanine aminotransferase (ALT) or aspartate aminotransferase (AST) were classified as having EAD type A, and the rest of the EAD patients were classified as having EAD type B. Recipients with EAD type B had lower graft and patient survival rates than recipients with EAD type A (P=0.043 and 0.044, respectively). We further developed a nomogram to predict EAD (graft weight, cold ischemia time, donor age, model for end-stage liver disease (MELD) score) and another nomogram to predict EAD type B (graft weight, cold ischemia time, MELD score). The nomograms for the prediction of EAD and EAD type B had good discrimination [concordance index (C-index) =0.712 (0.666-0.758), 0.707 (0.641-0.773)] and calibration [Hosmer-Lemeshow (HL) P=0.384, P=0.425] in the validation cohort. An increased operative time (>6 h) was associated with increased EAD and EAD type B incidence in the high-risk group (P=0.005, P=0.020, respectively). CONCLUSIONS: EAD type B was associated with decreased graft and patient survival rates. The novel nomograms effectively predicted the incidence of EAD and EAD type B in DCD LT patients.