NiCo2O4@SnS2nanosheets on carbon cloth as efficient bi-functional material for high performance supercapacitor and sensor applications.

Bi-functional materials provide an opportunity for the development of high-performance devices. Up till now, bi-functional performance of NiCo2O4@SnS2nanosheets is rarely investigated. In this work, NiCo2O4@SnS2nanosheets were synthesized on carbon cloth by utilizing a simple hydrothermal technique. The developed electrode (NiCo2O4@SnS2/CC) was investigated for the detection of L-Cysteine and supercapacitors applications. As a non-enzymatic sensor, the electrode proved to be highly sensitive for the detection of L-cysteine. The electrode exhibits a reproducible sensitivity of 4645.82µA mM-1cm-2in a wide linear range from 0.5 to 5 mM with a low limit of detection (0.005µM). Moreover, the electrode shows an excellent selectivity and long-time stability. The high specific surface area, enhanced kinetics, good synergy and distinct architecture of NiCo2O4@SnS2nanosheets produce a large number of active sites with substantial energy storage potential. As a supercapacitor, the electrode exhibits improve capacitance of 655.7 F g-1at a current density of 2 A g-1as compare to NiCo2O4/CC (560 F g-1). Moreover, the electrode achieves 95.3% of its preliminary capacitance after 10 000 cycles at 2 A g-1. Our results show that NiCo2O4@SnS2/CC nanosheets possess binary features could be attractive electrode material for the development of non-enzymatic biosensors as well as supercapacitors.

Novel, high accuracy models for hepatocellular carcinoma prediction based on longitudinal data and cell-free DNA signatures.

BACKGROUND & AIMS: Current hepatocellular carcinoma (HCC) risk scores do not reflect changes in HCC risk resulting from liver disease progression/regression over time. We aimed to develop and validate two novel prediction models using multivariate longitudinal data, with or without cell-free DNA (cfDNA) signatures. METHODS: A total of 13,728 patients from two nationwide multicenter prospective observational cohorts, the majority of whom had chronic hepatitis B, were enrolled. aMAP score, as one of the most promising HCC prediction models, was evaluated for each patient. Low-pass whole-genome sequencing was used to derive multi-modal cfDNA fragmentomics features. A longitudinal discriminant analysis algorithm was used to model longitudinal profiles of patient biomarkers and estimate the risk of HCC development. RESULTS: We developed and externally validated two novel HCC prediction models with a greater accuracy, termed aMAP-2 and aMAP-2 Plus scores. The aMAP-2 score, calculated with longitudinal data on the aMAP score and alpha-fetoprotein values during an up to 8-year follow-up, performed superbly in the training and external validation cohorts (AUC 0.83-0.84). The aMAP-2 score showed further improvement and accurately divided aMAP-defined high-risk patients into two groups with 5-year cumulative HCC incidences of 23.4% and 4.1%, respectively (p = 0.0065). The aMAP-2 Plus score, which incorporates cfDNA signatures (nucleosome, fragment and motif scores), optimized the prediction of HCC development, especially for patients with cirrhosis (AUC 0.85-0.89). Importantly, the stepwise approach (aMAP -> aMAP-2 -> aMAP-2 Plus) stratified patients with cirrhosis into two groups, comprising 90% and 10% of the cohort, with an annual HCC incidence of 0.8% and 12.5%, respectively (p <0.0001). CONCLUSIONS: aMAP-2 and aMAP-2 Plus scores are highly accurate in predicting HCC. The stepwise application of aMAP scores provides an improved enrichment strategy, identifying patients at a high risk of HCC, which could effectively guide individualized HCC surveillance. IMPACT AND IMPLICATIONS: In this multicenter nationwide cohort study, we developed and externally validated two novel hepatocellular carcinoma (HCC) risk prediction models (called aMAP-2 and aMAP-2 Plus scores), using longitudinal discriminant analysis algorithm and longitudinal data (i.e., aMAP and alpha-fetoprotein) with or without the addition of cell-free DNA signatures, based on 13,728 patients from 61 centers across mainland China. Our findings demonstrated that the performance of aMAP-2 and aMAP-2 Plus scores was markedly better than the original aMAP score, and any other existing HCC risk scores across all subsets, especially for patients with cirrhosis. More importantly, the stepwise application of aMAP scores (aMAP -> aMAP-2 -> aMAP-2 Plus) provides an improved enrichment strategy, identifying patients at high risk of HCC, which could effectively guide individualized HCC surveillance.

Mesoporous NiCo2S4nanoflakes as an efficient and durable electrocatalyst for non-enzymatic detection of cholesterol.

The detection of cholesterol is very crucial in clinical diagnosis for rapid and accurate monitoring of multiple disease-biomarkers. There is a great need for construction of a highly reliable and stable electrocatalyst for the efficient detection of cholesterol. In this work, mesoporous NiCo2S4nanoflakes of enhanced electrochemical properties are prepared through a facile hydrothermal approach. The developed nanoflakes modified nickel foam electrode exhibits outstanding electrocatalytic properties for the detection of cholesterol with high selectivity. The electrode displays excellent sensitivity of 8623.6µA mM-1cm-2, in the wide linear range from 0.01 to 0.25 mM with a low detection limit of 0.01µM. In addition, NiCo2S4structure reveals good thermal stability and reproducibility over a period of 8 weeks. Moreover, the nanoflakes show good response for detection of cholesterol in real samples. Our results demonstrate the potential use of NiCo2S4as a catalyst for the development of cost-effective electrochemical sensors for medical and industrial applications.

MiR-29b expression is associated with a dexmedetomidine-mediated protective effect against oxygen-glucose deprivation-induced injury to SK-N-SH cells in vitro.

Ischemic cerebral stroke is a leading cause of death and long-term disability world-wide. Neuronal injury following cerebral ischemia initiates a complex series of signaling cascades that lead to neuronal cell death. MicroRNA 29b (miR-29b) has reported involvement in the pathogenic process of ischemic brain injury. Dexmedetomidine (Dex) is a highly selective α2 adrenergic receptor stimulant that exerts a protective effect on brain tissue. To determine whether Dex might directly influence miR-29b expression after an ischemic injury, human neuroblastoma SK-N-SH cells were subjected to oxygen-glucose deprivation (OGD) for the purpose of creating a neuronal injury model that mimics the effects of brain ischemia in vitro. Next, the association of miR-29b with the protective effect of Dex against ischemic brain injury was studied through the enhancement or inhibition of miR-29b expression by transfection with an miR-29b mimic or inhibitor. We demonstrated that Dex treatment could reduce miR-29b expression, increase cell viability, and inhibit cell apoptosis in the OGD-induced neuronal injury model in vitro. Furthermore, down-regulation of miR-29b expression produced effects on OGD-induced neuronal injuries that were similar to those produced by Dex treatment. Moreover, up-regulation of miR-29b reversed the protective effect of Dex treatment against OGD-induced neuronal injury. Therefore, down-regulation of miR-29b expression might play a role in anti-apoptotic signaling similar to that played by Dex. Elucidation of the role played by miR-29b in ischemia, and identification of a definite association between Dex and miR-29b may lead to the development of new strategies for treating ischemic brain injuries.

Decreasing the pressure of endotracheal tube cuff slowly with a constant speed can decrease coughing incidence during extubation: a randomized clinical trial.

BACKGROUND: To discuss whether decreasing the pressure of endotracheal tube cuff slowly with a constant speed can decrease the incidence of coughing during extubation. METHODS: Ninety patients undergoing elective noncardiac surgery under general anesthesia with endotracheal intubation were randomly divided into two groups: group P, the pilot balloon was connected to a syringe and an aneroid manometer through a three-way stopcock, respectively, and the decrease of cuff pressure was controlled at 3 cmH2O/s during deflating before extubation; group C, the pressure in endotracheal tube cuff was decreased suddenly with a syringe extracting the air from the cuff rapidly at once exactly before extubation. The incidence of coughing during extubation period was recorded. Mean arterial pressure (MAP) and heart rate (HR) were recorded before general anesthesia induction (T0), just before cuff deflation (T1), immediately after deflation (T2), at 1 min (T3), 3 min (T4), and 5 min after extubation (T5). The occurrence of adverse reactions was also recorded. RESULTS: The initiation of coughing during extubation period occurs at immediately the time of balloon deflation. Compared with group C, the incidence of coughing was significantly decreased (P = 0.001), MAP and HR were significantly decreased at T2-T4 and T2-T5, respectively (P < 0.05 for all), and the incidence of pharyngolaryngeal discomfort after extubation was significantly reduced (P = 0.021) in group P. CONCLUSIONS: Decreasing the pressure of endotracheal tube cuff slowly with a constant speed can significantly reduce the incidence of coughing during extubating period, stabilize hemodynamics, and reduce the incidence of adverse reactions.

Mesoporous Co3O4@CdS nanorods as anode for high-performance lithium ion batteries with improved lithium storage capacity and cycle life.

Transition metal oxides based anodes are facing crucial problems of capacity fading at long cycles and high rates due to electrode degradations. In this prospective, an effective strategy is employed to develop advanced electrode materials for lithium-ion batteries (LIBs). In the present work, a mesoporous Co3O4@CdS hybrid sructure is developed and investigated as anode for LiBs. The hybrid structure owning porous nature and large specific surface area, provides an opportunity to boost the lithium storage capabilities of Co3O4 nanorods. The Co3O4@CdS electrode delivers an initial discharge capacity of 1292 mA h g-1 at 0.1C and a very stable reversible capacity of 760 mA h g-1 over 200 cycles with a capacity retention rate of 92.7%. In addition, the electrode exhibits excellent cyclic stability even after 800 cycles and good rate performance as compared to previously reported electrodes. Moreover, density functional theory (DFT) and electrochemical impedance spectroscopy (EIS) confirm the enhanced kinetics of the Co3O4@CdS electrode. The efficient performance of the electrode may be due to the increased surface reactivity, abundant active sites/interfaces for rapid Li+ ion diffusion and the synergy between Co3O4 and CdS NPs. This work demonstrates that Co3O4@CdS hybrid structures have great potential for high performance batteries.

Early warning of hepatocellular carcinoma in cirrhotic patients by three-phase CT-based deep learning radiomics model: a retrospective, multicentre, cohort study.

Background: The diagnosis of hepatocellular carcinoma (HCC) often experiences latency, ultimately leading to unfavorable patient outcomes due to delayed therapeutic interventions. Our study is designed to develop and validate a model that employs triple-phase computerized tomography (CT)-based deep learning radiomics and clinical variables for early warning of HCC in patients with cirrhosis. Methods: We studied 1858 patients with cirrhosis primarily from the PreCar cohort (NCT03588442) between June 2018 and January 2020 at 11 centres, and collected triple-phase CT images and laboratory results 3-12 months prior to HCC diagnosis or non-HCC final follow-up. Using radiomics and deep learning techniques, early warning model was developed in the discovery cohort (n = 924), and then validated in an internal validation cohort (n = 231), and an external validation cohort from 10 external centres (n = 703). Findings: We developed a hybrid model, named ALARM model, which integrates deep learning radiomics with clinical variables, enabling early warning of the majority of HCC cases. The ALARM model effectively predicted short-term HCC development in cirrhotic patients with area under the curve (AUC) of 0.929 (95% confidence interval 0.918-0.941) in the discovery cohort, 0.902 (0.818-0.987) in the internal validation cohort, and 0.918 (0.898-0.961) in the external validation cohort. By applying optimal thresholds of 0.21 and 0.65, the high-risk (n = 221, 11.9%) and medium-risk (n = 433, 23.3%) groups, which covered 94.4% (84/89) of the patients who developed HCC, had significantly higher rates of HCC occurrence compared to the low-risk group (n = 1204, 64.8%) (24.3% vs 6.4% vs 0.42%, P < 0.001). Furthermore, ALARM also demonstrated consistent performance in subgroup analysis. Interpretation: The novel ALARM model, based on deep learning radiomics with clinical variables, provides reliable estimates of short-term HCC development for cirrhotic patients, and may have the potential to improve the precision in clinical decision-making and early initiation of HCC treatments. Funding: This work was supported by National Key Research and Development Program of China (2022YFC2303600, 2022YFC2304800), and the National Natural Science Foundation of China (82170610), Guangdong Basic and Applied Basic Research Foundation (2023A1515011211).

Cell-free DNA testing for early hepatocellular carcinoma surveillance.

BACKGROUND: Liver cirrhosis (LC) is the highest risk factor for hepatocellular carcinoma (HCC) development worldwide. The efficacy of the guideline-recommended surveillance methods for patients with LC remains unpromising. METHODS: A total of 4367 LCs not previously known to have HCC and 510 HCCs from 16 hospitals across 11 provinces of China were recruited in this multi-center, large-scale, cross-sectional study. Participants were divided into Stage Ⅰ cohort (510 HCCs and 2074 LCs) and Stage Ⅱ cohort (2293 LCs) according to their enrollment time and underwent Tri-phasic CT/enhanced MRI, US, AFP, and cell-free DNA (cfDNA). A screening model called PreCar Score was established based on five features of cfDNA using Stage Ⅰ cohort. Surveillance performance of PreCar Score alone or in combination with US/AFP was evaluated in Stage Ⅱ cohort. FINDINGS: PreCar Score showed a significantly higher sensitivity for the detection of early/very early HCC (Barcelona stage A/0) in contrast to US (sensitivity of 51.32% [95% CI: 39.66%-62.84%] at 95.53% [95% CI: 94.62%-96.38%] specificity for PreCar Score; sensitivity of 23.68% [95% CI: 14.99%-35.07%] at 99.37% [95% CI: 98.91%-99.64%] specificity for US) (P < 0.01, Fisher's exact test). PreCar Score plus US further achieved a higher sensitivity of 60.53% at 95.08% specificity for early/very early HCC screening. INTERPRETATION: Our study developed and validated a cfDNA-based screening tool (PreCar Score) for HCC in cohorts at high risk. The combination of PreCar Score and US can serve as a promising and practical strategy for routine HCC care. FUNDING: A full list of funding bodies that contributed to this study can be found in Acknowledgments section.

Phosphorus vacancies improve the hydrogen evolution of MoP electrocatalysts.

Although molybdenum phosphide (MoP) has attracted increasing attention as an electrocatalyst in the hydrogen evolution reaction (HER), it is still worth exploring an effective approach to further improve the HER activities of MoP. To date, the generation and effect of P vacancies (Pv) on MoP have been rarely investigated for the HER in both alkaline and acidic media and remain unclear. Here, MoP rich in P vacancies (MoP-Pv) was prepared by hydrogen reduction to improve the HER catalytic performances. As a result, the overpotentials of MoP-Pv were 70 mV and 62 mV lower than those of pristine MoP in 1 M KOH and 0.5 M H2SO4 electrolytes, respectively. What's more, the TOFs of MoP-Pv were 3.14 s-1 and 1.19 s-1 at an overpotential of 200 mV in 1 M KOH and 0.5 M H2SO4, respectively, which are 4.1-fold and 2.5-fold higher than those of pristine MoP. Even when compared with other corresponding catalysts, the TOFs of MoP-Pv still ranked at the top. Due to the surface P vacancies, MoP-Pv possesses more electrochemically active sites and faster charge transfer capability, which all favor higher HER catalytic activities. Overall, our work validates a straightforward and vigorous strategy for improving the intrinsic HER catalytic activities of P vacancies, and also provides guidance for the development of vacancy engineering in electrocatalysts.

Median Effective Dose of Remifentanil for the Prevention of Pain Caused by the Injection of Rocuronium: An Age-Stratified Study.

INTRODUCTION: Rocuronium intravenous pain is common in induction of general anesthesia. The aim of our study was to determine the median effective dose (ED50) of prophylactic intravenous remifentanil for the prevention of rocuronium injection pain and to explore the effect of age on the ED50. METHODS: Eighty-nine adult patients undergoing elective general anesthesia, ASA I or II, regardless of gender or weight, were stratified according to age: group R1 18-44 years, group R2 45-59 years, and group R3 60-80 years. The initial dose of prophylactic remifentanil before rocuronium injection was set at 1 µg/kg lean body weight (LBW). The remifentanil doses were adjusted according to the degree of injection pain using the Dixon sequential method, with a ratio of 1.1 between adjacent doses. Injection pain was graded, and the occurrence of injection pain and adverse reactions were recorded. The ED50 and 95% confidence intervals (CIs) of remifentanil were calculated using the Dixon-Massey formula. Patients were asked whether they recalled feeling any injection pain in the post-anesthesia care unit (PACU). RESULTS: The ED50 (95% CIs) of prophylactic remifentanil for the prevention of rocuronium injection pain were 1.266 µg/kg (1.186-1.351 µg/kg), 1.188 µg/kg (1.065-1.324 µg/kg), and 1.070 µg/kg (1.014-1.129 µg/kg) LBW in group R1, group R2, and group R3, respectively. No adverse reactions to remifentanil occurred in any group. In PACU, 84.6, 86.7, and 85.7% of patients who experienced injection pain had memories of the pain in group R1, group R2, and group R3, respectively. CONCLUSIONS: Prophylactic intravenous remifentanil can prevent rocuronium injection pain, and its ED50 decreases with age, with 1.266 µg/kg (18-44 years), 1.188 µg/kg (45-59 years), and 1.070 µg/kg LBW (60-80 years), respectively. TRIAL REGISTRATION: ClinicalTrials.gov: NCT05217238 (registration date 18 Dec 2021).

Stellate ganglion block alleviates postoperative sleep disturbance in patients undergoing radical surgery for gastrointestinal malignancies.

STUDY OBJECTIVES: We explored the effects of stellate ganglion block on postoperative sleep disturbance in patients scheduled to undergo radical surgery for gastrointestinal malignancies. METHODS: Forty such patients were randomly assigned to the control group (Group C) or the preoperative stellate ganglion block treatment group (Group S). Using actigraphy, sleep quality was evaluated on the first night before the operation and first, second, and third postoperative nights. The Pittsburgh Sleep Quality Index scale was used for sleep state assessment on 1 day preoperatively and the first, second, third, fifth, and seventh days postoperatively. Plasma interleukin (IL)-1, IL-6, and IL-10 and melatonin levels were checked at 1 day preoperatively and the first and third days postoperatively. Mean arterial pressure, heart rate, and pulse oxygen saturation (SpO2) were recorded before general anesthesia induction, immediately after tracheal intubation, at the beginning of the operation, 1 and 2 hours after the beginning of the operation, at the end of the operation, immediately after extubation, and 30 minutes after transfer to the postanesthesia care unit. RESULTS: Compared with Group C, in Group S sleep efficiency, total sleep time, and sleep maintenance were increased and sleep period change index, number of awakenings, wake after sleep onset, and body movements were reduced on the first and second postoperative nights; Pittsburgh Sleep Quality Index scores and occurrence of postoperative sleep disturbance were lower on the first and second nights postoperatively; IL-6 was reduced on the first night postoperatively; IL-1 and IL-10 were reduced on the third night postoperatively; melatonin was increased on the first night postoperatively; and mean arterial pressure and heart rate were decreased before general anesthesia induction, immediately after tracheal intubation, and at the end of the operation (all P < .05). Conclusions: Stellate ganglion block alleviates postoperative sleep disturbance by reducing postoperative inflammatory response, increasing melatonin levels, and stabilizing perioperative hemodynamics in patients undergoing radical surgery for gastrointestinal malignancies. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: The Effect of Stellate Ganglion Block on Postoperative Sleep Disturbance and Cognitive Function in Elderly Surgical Patients; URL: https://clinicaltrials.gov/ct2/show/NCT04800653; Identifier: NCT04800653. CITATION: Yan S, Wang Y, Yu L, et al. Stellate ganglion block alleviates postoperative sleep disturbance in patients undergoing radical surgery for gastrointestinal malignancies. J Clin Sleep Med. 2023;19(9):1633-1642.

Pupillary monitoring decreases remifentanil consumption during laparoscopic uterine surgery and improves postoperative recovery.

BACKGROUND: The aim of this paper was to explore pupillary monitoring for determining remifentanil consumption during general anesthesia and evaluating postoperative recovery quality. METHODS: Eighty patients undergoing elective laparoscopic uterine surgery were randomly divided into pupillary monitoring group (Group P) and control group (Group C). In Group P, remifentanil dosage during general anesthesia was determined according to pupil dilation reflex; in Group C, it was adjusted according to hemodynamic changes. Intraoperative remifentanil consumption and endotracheal tube extraction time were recorded. The Numerical Rating Scale (NRS) Score, hemodynamic changes, and opioid-related adverse reactions in the post-anesthesia care unit were also recorded. The parameters of pupil light reflex from extubation to 30 min after extubation were analyzed in Group P, and the responsiveness of these parameters and hemodynamic changes to NRS was determined by ROC curve analyses. RESULTS: Compared with Group C, in Group P, intraoperative remifentanil consumption, the NRS Score at 20 minutes after extubation, extubation time, and the incidence of nausea, vomiting, and respiratory amnesia were all significantly decreased (all, P<0.05). In Group P, ∆HR and ∆MAP had no value in judging the change of NRS. The ROC values and diagnostic cutoff values of ΔInit, ΔACV, and ΔMCV responding to NRS variation were 0.775 (95% CI: 0.582-0.968), 0.734(95% CI: 0.537-0.930), and 0.822 (95% CI: 0.648-0.997) and 0.21 (sensitivity, 92.3%; specificity, 23.1%), -1.3 (sensitivity, 92.3%; specificity, 18.3%), and -1.0 (sensitivity, 84.6%; specificity, 17.7%), respectively. CONCLUSIONS: Intraoperative pupil dilation reflex monitoring can reduce remifentanil consumption and improve postoperative recovery quality. Furthermore, postoperative pupil light reflex monitoring can help evaluate pain degree with high sensitivity.

Extract of Ginkgo biloba leaves attenuates neurotoxic damages in rats and SH-SY5Y cells exposed to a high level of fluoride.

BACKGROUND: Potential protection against the neurotoxic damages of high levels of fluoride on rats and SH-SY5Y cells by extract of Ginkgo biloba leaves, as well as underlying mechanisms, were examined. METHODS: The rats were divided randomly into 4 groups, i.e., control, treatment with the extract (100 mg/kg body weight, gavage once daily), treatment with fluoride (50 ppm F- in drinking water) and combined treatment with both; SH-SY5Y cells exposed to fluoride and fluoride in combination with the extract or 4-Amino-1,8-naphthalimide (4-ANI), an inhibitor of poly (ADP-ribose) polymerase-1 (PARP-1). Spatial learning and memory in the rats were assessed employing Morris water maze test; the contents of fluoride in brains and urine by fluoride ion-selective electrode; cytotoxicity of fluoride was by CCK-8 kit; the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and the content of malondialdehyde (MDA) by appropriate kits; the level of 8-hydroxydeoxyguanosine (8-OHdG) was by ELISA; the content of ROS and frequency of apoptosis by flow cytometry; the expressions of phospho-histone H2A.X(Ser139), PARP-1, poly (ADP-ribose) (PAR) and Sirtuin-1 (SIRT1) by Western blotting or immunofluorescence. RESULTS: The rats with prolong treatment of fluoride exhibited dental fluorosis, the increased contents of fluoride in brains and urine and the declined ability of learning and memory. In the hippocampus of the rats and SH-SY5Y cells exposed to fluoride, the levels of ROS, MDA, apoptosis, 8-OHdG and the protein expressions of histone H2A.X(Ser139), PARP-1 and PAR were all elevated; the activities of SOD and GSH-Px and the protein expression of SIRT1 reduced. Interestingly, the treatment of Ginkgo biloba extract attenuated these neurotoxic effects on rats and SH-SY5Y cells exposed to fluoride and the treatment of 4-ANI produced a neuroprotective effect against fluoride exposure. CONCLUSION: Ginkgo biloba extract attenuated neurotoxic damages induced by fluoride exposure to rats and SH-SY5Y cells and the underlying mechanism might involve the inhibition of PARP-1 and the promotion of SIRT1.

The development of a cSMART-based integrated model for hepatocellular carcinoma diagnosis.

BACKGROUND: Hepatocellular carcinoma (HCC) generally arises from a background of liver cirrhosis (LC). Patients with cirrhosis and suspected HCC are recommended to undergo serum biomarker tests and imaging diagnostic evaluation. However, the performance of routine diagnostic methods in detecting early HCC remains unpromising. METHODS: Here, we conducted a large-scale, multicenter study of 1675 participants including 490 healthy controls, 577 LC patients, and 608 HCC patients from nine clinical centers across nine provinces of China, profiled gene mutation signatures of cell-free DNA (cfDNA) using Circulating Single-Molecule Amplification and Resequencing Technology (cSMART) through detecting 931 mutation sites across 21 genes. RESULTS: An integrated diagnostic model called "Combined method" was developed by combining three mutation sites and three serum biomarkers. Combined method outperformed AFP in the diagnosis of HCC, especially early HCC, with sensitivities of 81.25% for all stages and 66.67% for early HCC, respectively. Importantly, the integrated model exhibited high accuracy in differentiating AFP-negative, AFP-L3-negative, and PIVKA-II-negative HCCs from LCs.

Fluoride Exposure Suppresses Proliferation and Enhances Endoplasmic Reticulum Stress and Apoptosis Pathways in Hepatocytes by Downregulating Sirtuin-1.

Objective: To explore the function and mechanism of Sirt-1 in fluorine-induced liver injury. Method: Fluorosis rats were first established. The fluorine content, pathological structure, collagen fibers, and fibrosis in liver tissues were tested through the fluoride ion selective electrode method, H&E, Masson, and Sirius red staining; alanine aminotransferase (ALT), aspartate aminotransferase (AST), interleukin 18 (IL-18), and tumor necrosis factor-α (TNF-α) levels in rat serum were also analyzed using ELISA kits. Then, the fluorosis cell model was built, which was also alleviated with NaF, Sirt-1 siRNAs, or endoplasmic reticulum stress (ERS) alleviator (4-PBA). CCK-8 also assessed cell proliferation; RT-qPCR or Western blots detect sirtuin-1 (Sirt-1), protein kinase R- (PKR-) like endoplasmic reticulum kinase (PERK), and endoplasmic reticulum stress (ERS) and apoptosis-related protein levels in liver tissue. Results: Our results uncovered that fluorine exposure could aggravate the pathological damage and fibrosis of rat liver tissues and increase indicators related to liver injury. And fluoride exposure also could downregulate Sirt-1 and upregulate ERS-related proteins (PERK, 78-kD glucose-regulated protein (GRP-78), and activating transcription factor 6 (ATF6)) and apoptosis-related protein (caspase-3 and C/EBP-homologous protein (CHOP)) in rat liver tissues. Besides, we proved that fluoride exposure could suppress proliferation and enhances ERS and apoptotic pathways in AML12 cells by downregulating Sirt-1. Moreover, we revealed that ERS alleviator (4-PBA) could induce proliferation and prevent ERS and apoptosis in fluorine-exposed AML12 cells. Conclusions: We suggested that fluorine exposure can induce hepatocyte ERS and apoptosis through downregulation of Sirt-1.

Multi-Effect Enhanced Raman Scattering Based on Au/ZnO Nanorods Structures.

Surface-enhanced Raman scattering (SERS) was considered a potential spectroscopic technique for applications of molecular detection and has drawn great research interest during the past decade. So far, fabrications of cost-effective SERS substrates with high sensitivity and stability and the corresponding enhanced mechanisms are always among the list of research topics, although great progress has been made. In this work, Au particles were decorated on Si, ZnO film and ZnO nanorod arrays simultaneously by an economical method of ion sputtering, generating three kinds of SERS substrates for R6G detection. The morphology difference of Au particles on different samples and the consequent influence on Raman scattering were studied. The experiment results exhibited that substrates with Au particles decorated on ZnO nanorods had the highest Raman enhancement factor. Furthermore, multi-effect enhanced mechanisms summarized as localized surface plasmon resonance (LSPR) filed coupling, electron transferring induced by LSPR of Au particles and whispering gallery mode (WGM) effect of the ZnO cavity were presented. This work provides a convenient and efficient method of fabricating SERS substrates and indicates that such proper metal/semiconductor composite structures are promising candidates for SERS applications.

Ubiquitin­specific peptidase 53 promotes chronic constriction injury­induced neuropathic pain through the RhoA/ROCK pathway.

Neuropathic pain is associated with nervous system injury and the production of pro­inflammatory factors. Critical functions for ubiquitin­specific peptidase 53 (USP53) have been demonstrated in various diseases. However, the role and mechanism of USP53 in chronic constriction injury (CCI)­induced neuropathic remains unclear. In our current study, a model of neuropathic pain was induced by CCI in rats. Quantitative reverse transcription­polymerase chain reaction (qRT­PCR) and western blotting results demonstrated that USP53 was significantly up­regulated in CCI rats. In addition, silencing of USP53 alleviated neuropathic pain and reduced the production of pro­inflammatory factors in CCI rats according to paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) tests and enzyme­linked immunosorbent assay (ELISA), respectively. Moreover, knockdown of USP53 inhibited the activation of FK506­binding protein 51 (FKBP51)/RhoA/ROCK signaling in CCI rats. In summary, this study revealed that USP53 exacerbated CCI­induced neuropathic pain, potentially via regulation of the FKBP51/RhoA/ROCK pathway.

The Landscape of Cell-Free HBV Integrations and Mutations in Cirrhosis and Hepatocellular Carcinoma Patients.

PURPOSE: Intratumoral hepatitis B virus (HBV) integrations and mutations are related to hepatocellular carcinoma (HCC) progression. Circulating cell-free DNA (cfDNA) has shown itself as a powerful noninvasive biomarker for cancer. However, the HBV integration and mutation landscape on cfDNA remains unclear. EXPERIMENTAL DESIGN: A cSMART (Circulating Single-Molecule Amplification and Resequencing Technology)-based method (SIM) was developed to simultaneously investigate HBV integration and mutation landscapes on cfDNA with HBV-specific primers covering the whole HBV genome. Patients with HCC (n = 481) and liver cirrhosis (LC; n = 517) were recruited in the study. RESULTS: A total of 6,861 integration breakpoints including TERT and KMT2B were discovered in HCC cfDNA, more than in LC. The concentration of circulating tumor DNA (ctDNA) was positively correlated with the detection rate of these integration hotspots and total HBV integration events in cfDNA. To track the origin of HBV integrations in cfDNA, whole-genome sequencing (WGS) was performed on their paired tumor tissues. The paired comparison of WGS data from tumor tissues and SIM data from cfDNA confirmed most recurrent integration events in cfDNA originated from tumor tissue. The mutational landscape across the whole HBV genome was first generated for both HBV genotype C and B. A region from nt1100 to nt1500 containing multiple HCC risk mutation sites (OR > 1) was identified as a potential HCC-related mutational hot zone. CONCLUSIONS: Our study provides an in-depth delineation of HBV integration/mutation landscapes at cfDNA level and did a comparative analysis with their paired tissues. These findings shed light on the possibilities of noninvasive detection of virus insertion/mutation.

Direct Synthesis of Atomically Dispersed Palladium Atoms Supported on Graphitic Carbon Nitride for Efficient Selective Hydrogenation Reactions.

Heterogeneous catalysts with atomically precise metal sites have enabled unique insight into structure-property relationships in materials science. Herein, we report the construction and selective hydrogenation performance of a single-atom palladium catalyst by confining the palladium atoms into the six-fold N-coordinating cavities of graphitic carbon nitride (g-C3N4) through a facile spatial confinement-reduction approach under mild reducing conditions. Spherical aberration correction electron microscopy and extended X-ray absorption fine structure measurements confirm the presence of atomically dispersed palladium atoms stabilized by the g-C3N4 support. Its exceptional catalytic activity was demonstrated by the hydrogenation of styrene (98% conversion, 1.5 h) and furfural (conversion of 64% and selectivity of 99%, 4 h) and hydrodechlorination of 4-chlorophenol (99% conversion and 99% selectivity, 10 min). This palladium catalyst can be reused at least five times with negligible deterioration of its activity. Importantly, the palladium atoms retained their atomic dispersion following the thermal treatment. Moreover, this synthetic method can be scaled up while retaining similar catalytic activity. Fundamental insights are provided to elucidate how the material's structure significantly impacts the catalytic performance at the atomic scale.

Animal heat activated cancer therapy by a traditional catalyst TiO2-Pd/graphene composites.

Cancer therapy is one of the most important challenges in clinical medicine. So far different methods have been developed for cancer therapy, such as radiation therapy, surgery, chemotherapy and photodynamic therapy. Here we propose a new concept for cancer therapy, i.e., killing the cancer cells simply via reactive oxygen species (ROS) generated by TiO2-Pd/graphene composites. Activated by animal heat of 37 °C, the electrons in the valence band can be excited to the conduction band of TiO2 via the energy levels of Pd species and graphene, generating ROS without light irradiation or electric excitation. The tumors in BALB/c mice are successfully regressed at animal heat without any other external conditions, such as radiation, UV, visible and IR irradiation. Our results suggest that the design of animal heat activated cancer therapy is a feasible concept for practical applications of cancer treatments.