Tenecteplase versus alteplase in acute ischaemic cerebrovascular events (TRACE-2): a phase 3, multicentre, open-label, randomised controlled, non-inferiority trial.

BACKGROUND: There is increasing interest in replacing alteplase with tenecteplase as the preferred thrombolytic treatment for patients with acute ischaemic stroke. We aimed to establish the non-inferiority of tenecteplase to alteplase for these patients. METHODS: In this multicentre, prospective, open-label, blinded-endpoint, randomised controlled, non-inferiority trial, adults with an acute ischaemic stroke who were eligible for standard intravenous thrombolysis but ineligible for endovascular thrombectomy were enrolled from 53 centres in China and randomly assigned (1:1) to receive intravenous tenecteplase (0·25 mg/kg, maximum dose of 25 mg) or intravenous alteplase (0·9 mg/kg, maximum dose of 90 mg). Participants had to be able to receive treatment within 4·5 h of stroke, have a modified Rankin Scale (mRS) score of no more than 1 before enrolment, and have a National Institutes of Health Stroke Scale score of 5-25. Patients and treating clinicians were not masked to group assignment; clinicians evaluating outcomes were masked to treatment type. The primary efficacy outcome was the proportion of participants who had a mRS score of 0-1 at 90 days, assessed in the modified intention-to-treat population (all randomly assigned participants who received the allocated thrombolytic), with a non-inferiority margin of 0·937 for the risk ratio (RR). The primary safety outcome was symptomatic intracranial haemorrhage within 36 h, assessed in all participants who received study drug and had a safety assessment available. The trial is registered with ClinicalTrials.gov, NCT04797013, and has been completed. FINDINGS: Between June 12, 2021, and May 29, 2022, 1430 participants were enrolled and randomly assigned to tenecteplase (n=716) or alteplase (n=714). Six patients assigned to tenecteplase and seven to alteplase did not receive study product, and five participants in the tenecteplase group and 11 in the alteplase group were lost to follow-up at 90 days. The primary outcome in the modified intention-to-treat population occurred in 439 (62%) of 705 in the tenecteplase group versus 405 (58%) of 696 in the alteplase group (RR 1·07, 95% CI 0·98-1·16). The lower limit of the RR's 95% CI was greater than the non-inferiority margin. Symptomatic intracranial haemorrhage within 36 h was observed in 15 (2%) of 711 in the tenecteplase group and 13 (2%) of 706 in the alteplase group (RR 1·18, 95% CI 0·56-2·50). Mortality within 90 days occurred in 46 (7%) individuals in the tenecteplase group versus 35 (5%) in the alteplase group (RR 1·31, 95% CI 0·86-2·01). INTERPRETATION: Tenecteplase was non-inferior to alteplase in people with ischaemic stroke who were eligible for standard intravenous thrombolytic but ineligible for or refused endovascular thrombectomy. FUNDING: National Science and Technology Major Project, Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, National Natural Science Foundation of China, and China Shijiazhuang Pharmaceutical Company Recomgen Pharmaceutical (Guangzhou).

Association between drug craving and aggression in Chinese male methamphetamine-dependent patients with and without depressive symptoms.

Depressive symptoms and aggression are common in patients with substance use disorder. Drug craving is one of the main drivers of drug-seeking behavior. This study aimed to explore the relationship between drug craving and aggression in methamphetamine use disorder (MAUD) patients with and without depressive symptoms. Totally, 613 male patients with MAUD were recruited in this study. Patients with depressive symptoms were identified by the 13-item Beck Depression Inventory (BDI-13). Drug craving and aggression were assessed by the Desires for Drug Questionnaire (DDQ) and the Buss & Perry Aggression Questionnaire (BPAQ), respectively. 374 patients (61.01%) were confirmed to meet the criteria of depressive symptoms. Patients with depressive symptoms had significantly higher DDQ and BPAQ total scores than those without depressive symptoms. DDQ desire and intention were positively correlated with verbal aggression and hostility in patients with depressive symptoms, whereas they were correlated with self-directed aggression in patients without depressive symptoms. In patients with depressive symptoms, DDQ negative reinforcement and a history of suicide attempts were independently associated with BPAQ total score. Our study suggests that male MAUD patients have a high incidence of depressive symptoms and that patients with depressive symptoms may have greater drug cravings and aggression. Depressive symptoms may play a role in the association between drug craving and aggression in patients with MAUD.

Characterisation of a casein-/whey protein concentrate-Antarctic krill oil emulsion system and improvement of its storage stability.

AIMS: To develop Antarctic krill oil emulsions with casein and whey protein concentrate (WPC) and study their physicochemical properties and storage stability. METHODS: Emulsions were prepared by homogenisation and ultrasonication. The properties of the emulsions were investigated via ultraviolet ray spectroscopy, dynamic light scattering, confocal laser scanning microscope, sodium dodecyl sulphate-polyacrylamide gel electrophoresis, Fourier transform infra-red spectrometer, and fluorescence spectrum. Shelf life was predicted by the Arrhenius model. RESULTS: Casein- and WPC-krill oil emulsions were well formed; the mean particle diameters were less than 128.19 ± 0.64 nm and 158 ± 1.56 nm, the polymer dispersity indices were less than 0.26 ± 0.01 and 0.27 ± 0.01, and the zeta potential were around -46.88 ± 5.02 mV and -33.51 ± 2.68 mV, respectively. Shelf life was predicted to be 32.67 ± 1.55 days and 29.62 ± 0.65 days (40 °C), 27.69 ± 1.15 days and 23.58 ± 0.14 days (50 °C), 24.02 ± 0.15 days and 20.1 ± 0.08 days (60 °C). CONCLUSION: The prepared krill oil emulsions have great potential to become a new krill oil supplement.

Prediction differences and implications of acute kidney injury with and without urine output criteria in adult critically ill patients.

BACKGROUND: Due to the convenience of serum creatinine (SCr) monitoring and the relative complexity of urine output (UO) monitoring, most studies have predicted acute kidney injury (AKI) only based on SCr criteria. This study aimed to compare the differences between SCr alone and combined UO criteria in predicting AKI. METHODS: We applied machine learning methods to evaluate the performance of 13 prediction models composed of different feature categories on 16 risk assessment tasks (half used only SCr criteria, half used both SCr and UO criteria). The area under receiver operator characteristic curve (AUROC), the area under precision recall curve (AUPRC) and calibration were used to assess the prediction performance. RESULTS: In the first week after ICU admission, the prevalence of any AKI was 29% under SCr criteria alone and increased to 60% when the UO criteria was combined. Adding UO to SCr criteria can significantly identify more AKI patients. The predictive importance of feature types with and without UO was different. Using only laboratory data maintained similar predictive performance to the full feature model under only SCr criteria [e.g. for AKI within the 48-h time window after 1 day of ICU admission, AUROC (95% confidence interval) 0.83 (0.82, 0.84) vs 0.84 (0.83, 0.85)], but it was not sufficient when the UO was added [corresponding AUROC (95% confidence interval) 0.75 (0.74, 0.76) vs 0.84 (0.83, 0.85)]. CONCLUSIONS: This study found that SCr and UO measures should not be regarded as equivalent criteria for AKI staging, and emphasizes the importance and necessity of UO criteria in AKI risk assessment.

Nanoprecipitates of γ-cyclodextrin/epigallocatechin-3-gallate inclusion complexes as efficient antioxidants for preservation of shrimp surimi products: synthesis, performance and mechanism.

BACKGROUND: Epigallocatechin-3-gallate (EGCG) is well known for excellent chain-breaking antioxidant capability. However, browning by oxidation and aggregation of EGCG is a non-negligible defect that hinders its applications as an antioxidant in various foodstuffs. Therefore, how to eliminate or mitigate browning efficiently, while retaining functionalities as food additive is a challenge in the food industry. RESULTS: Our results demonstrated that EGCG could be anchored within the internal cavity of γ-cyclodextrin (γ-CD) to form an inclusion structure, where hydrophobic interaction, hydrogen bonding, and π-stacking were identified to be the primary drivers. The interplay between two molecules and the steric hindrance from γ-CD could restrict the motion and aggregation of EGCG efficiently, thus alleviating the browning effect. In addition, the conformational adaption of EGCG within the inclusions would result in general decreases in hydrogen-bond dissociation enthalpies for the pyrogallol-type structure on the b ring, thus enhancing the antioxidant capability. In practical application, the nanoscale γ-CD/EGCG inclusion complexes were validated preliminarily as efficient additives in the preservation of shrimp surimi, presenting significant effects on prolonging the shelf-life of products. CONCLUSION: Here, nanoscale γ-CD/EGCG inclusion complexes as alternatives to EGCG were tailored as food antioxidants for the preservation of shrimp surimi products, exerting antioxidant effects while mitigating the browning effects of EGCG on products. Through self-assembly, EGCG would be anchored with the cavity of γ-CD, which could regulate the release modes and restrict the aggregation of EGCG. This facile strategy has great potential in food preservation. © 2023 Society of Chemical Industry.

The STING pathway: Therapeutic vulnerabilities in ovarian cancer.

Ovarian cancer is the leading cause of mortality due to gynecologic malignancy. The majority of women diagnosed with the most common subtype, high-grade serous ovarian carcinoma (HGSC), develop resistance to conventional therapies despite initial response to treatment. HGSC tumors displaying DNA damage repair (DDR) gene deficiency and high chromosomal instability mainly associate with higher cytotoxic immune cell infiltration and expression of genes associated with these immune pathways. Despite the high level of immune infiltration observed, the majority of patients with HGSC have not benefited from immunomodulatory treatments as the mechanistic basis of this infiltration is unclear. This lack of response can be primarily attributed to heterogeneity at the levels of both cancer cell genetic alterations and the tumour immune microenvironment. Strategies to enhance anti-tumour immunity have been investigated in ovarian cancer, of which interferon activating therapies present as an attractive option. Of the several type I interferon (IFN-1) stimulating therapies, exogenously activating the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway is emerging as a promising avenue. Herein, we highlight our current understanding of how constitutive and induced cGAS-STING pathway activation influences the ovarian tumour microenvironment. We further elaborate on the links between the genomic alterations prevalent in ovarian tumours and how the resultant immune phenotypes can make them more susceptible to exogenous STING pathway activation and potentiate immune-mediated killing of cancer cells. The therapeutic potential of cGAS-STING pathway activation in ovarian cancer and factors implicating treatment outcomes are discussed, providing a rationale for future combinatorial treatment approaches on the backbone of chemotherapy.

Opening the black box: interpretable machine learning for predictor finding of metabolic syndrome.

OBJECTIVE: The internal workings ofmachine learning algorithms are complex and considered as low-interpretation "black box" models, making it difficult for domain experts to understand and trust these complex models. The study uses metabolic syndrome (MetS) as the entry point to analyze and evaluate the application value of model interpretability methods in dealing with difficult interpretation of predictive models. METHODS: The study collects data from a chain of health examination institution in Urumqi from 2017 ~ 2019, and performs 39,134 remaining data after preprocessing such as deletion and filling. RFE is used for feature selection to reduce redundancy; MetS risk prediction models (logistic, random forest, XGBoost) are built based on a feature subset, and accuracy, sensitivity, specificity, Youden index, and AUROC value are used to evaluate the model classification performance; post-hoc model-agnostic interpretation methods (variable importance, LIME) are used to interpret the results of the predictive model. RESULTS: Eighteen physical examination indicators are screened out by RFE, which can effectively solve the problem of physical examination data redundancy. Random forest and XGBoost models have higher accuracy, sensitivity, specificity, Youden index, and AUROC values compared with logistic regression. XGBoost models have higher sensitivity, Youden index, and AUROC values compared with random forest. The study uses variable importance, LIME and PDP for global and local interpretation of the optimal MetS risk prediction model (XGBoost), and different interpretation methods have different insights into the interpretation of model results, which are more flexible in model selection and can visualize the process and reasons for the model to make decisions. The interpretable risk prediction model in this study can help to identify risk factors associated with MetS, and the results showed that in addition to the traditional risk factors such as overweight and obesity, hyperglycemia, hypertension, and dyslipidemia, MetS was also associated with other factors, including age, creatinine, uric acid, and alkaline phosphatase. CONCLUSION: The model interpretability methods are applied to the black box model, which can not only realize the flexibility of model application, but also make up for the uninterpretable defects of the model. Model interpretability methods can be used as a novel means of identifying variables that are more likely to be good predictors.

Construction of Xinjiang metabolic syndrome risk prediction model based on interpretable models.

BACKGROUND: We aimed to construct simple and practical metabolic syndrome (MetS) risk prediction models based on the data of inhabitants of Urumqi and to provide a methodological reference for the prevention and control of MetS. METHODS: This is a cross-sectional study conducted in the Xinjiang Uygur Autonomous Region of China. We collected data from inhabitants of Urumqi from 2018 to 2019, including demographic characteristics, anthropometric indicators, living habits and family history. Resampling technology was used to preprocess the data imbalance problems, and then MetS risk prediction models were constructed based on logistic regression (LR) and decision tree (DT). In addition, nomograms and tree diagrams of DT were used to explain and visualize the model. RESULTS: Of the 25,542 participants included in the study, 3,267 (12.8%) were diagnosed with MetS, and 22,275 (87.2%) were diagnosed with non-MetS. Both the LR and DT models based on the random undersampling dataset had good AUROC values (0.846 and 0.913, respectively). The accuracy, sensitivity, specificity, and AUROC values of the DT model were higher than those of the LR model. Based on a random undersampling dataset, the LR model showed that exercises such as walking (OR=0.769) and running (OR= 0.736) were protective factors against MetS. Age 60 ~ 74 years (OR=1.388), previous diabetes (OR=8.902), previous hypertension (OR=2.830), fatty liver (OR=3.306), smoking (OR=1.541), high systolic blood pressure (OR=1.044), and high diastolic blood pressure (OR=1.072) were risk factors for MetS; the DT model had 7 depth layers and 18 leaves, with BMI as the root node of the DT being the most important factor affecting MetS, and the other variables in descending order of importance: SBP, previous diabetes, previous hypertension, DBP, fatty liver, smoking, and exercise. CONCLUSIONS: Both DT and LR MetS risk prediction models have good prediction performance and their respective characteristics. Combining these two methods to construct an interpretable risk prediction model of MetS can provide methodological references for the prevention and control of MetS.

Characterization of a synthetic zinc-chelating peptide from sea cucumber (Stichopus japonicus) and its gastrointestinal digestion and absorption in vitro.

BACKGROUND: Zinc absorption in intestinal system could be strongly affected by the gastrointestinal digestion and absorption of zinc-chelating peptides serving as zinc carriers. In this study, a novel zinc-chelating sea cucumber synthetic peptide (SCSP) was synthesized to estimate its gastrointestinal digestion and promotive effect of zinc absorption in vitro. RESULTS: Analysis of isothermal titration calorimetry suggested that the binding of SCSP and zinc (N ≈ 1) was exothermic, with relatively weak binding affinity (K = 1.0 × 10-3  mol L-1 ). The formation of SCSP-Zn complexes brought morphological changes to the peptides confirmed by scanning electron microscopy (SEM), which also indicated 6.88% of the existence of zinc element. In addition, the SCSP-Zn complexes remained stable under simulated human gastrointestinal digestion. In an in vitro study, the SCSP-Zn complex could successfully transport through the intestinal membrane in the model of everted rat gut sacs (nearly 7.5 µM cm-2 ) as well as Caco-2 cells where the zinc transport reached 0.0014 mg mL-1 carried by SCSP. Fluorescence staining experiments revealed free zinc accumulation inside the tissues and cells treated with the SCSP-Zn complex. CONCLUSIONS: The chelation SCSP-Zn had the promotion ability of zinc absorption in vitro and ex vivo experiments, which suggested a theoretical basis for the design and production of effective zinc chelating peptides as zinc carriers to improve zinc bioavailability. © 2022 Society of Chemical Industry.

Differences in oxidative susceptibilities between glycerophosphocholine and glycerophosphoethanolamine in dried scallop (Argopecten irradians) adductor muscle during storage: an oxidation kinetic assessment.

BACKGROUND: Phospholipids, the main lipid component in marine shellfish, mainly comprise glycerophosphocholine (GPC) and glycerophosphoethanolamine (GPE). GPC and GPE in marine shellfish, especially scallop, carry n-3 long-chain polyunsaturated fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), although different types of glycerophospholipids (GP) have different health benefits on human health. Moreover, different GP subclasses such as GPC and GPE have different oxidative susceptibilities in complex food systems. The present study compared the oxidative susceptibilities of GPC and GPE in dried scallop during storage by high-performance liquid chromatography-tandem mass spectrometry and kinetic models, and also investigated the effects of natural phenolic antioxidant on their susceptibilities. RESULTS: The results showed that GPC and GPE molecular species (carrying EPA or DHA) contents in samples continuously reduced during storage at two different temperatures. The first-order kinetic model better reflected the changes of GPC and GPE molecular species (carrying EPA or DHA) in samples than the zero-order kinetic model during storage. According to the oxidation rate (k) obtained from first-order kinetic models, GPE possessed a greater oxidation rate than GPC during storage. Moreover, the results showed that antioxidants of bamboo leaves (AOB, polar polyphenolic antioxidants) significantly decreased the oxidation rates of GPC and GPE molecular species (carrying EPA or DHA) in samples during storage, and GPC could be more effectively protected by AOB compared to GPE. CONCLUSION: The present study provides a practical method for accurately evaluating the oxidative susceptibility of different phospholipid classes in complex food systems. © 2020 Society of Chemical Industry.

MIF -173G/C (rs755622) polymorphism modulates coronary artery disease risk: evidence from a systematic meta-analysis.

BACKGROUND: Coronary artery disease (CAD) remains one of the major causes of death in humans. Genetic testing may allow early detection and prevention of this disease. This study aimed to investigate the association between the macrophage migration inhibitory factor (MIF) -173G/C (rs755622) polymorphism and susceptibility to CAD based on a meta-analysis. METHODS: We searched several databases to identify observational case-control studies investigating the association between the MIF -173G > C (rs755622) polymorphism and CAD risk published before July 30, 2019. Data were analyzed using the STATA software. RESULTS: Six studies, comprising a total of 1172 CAD cases and 1564 controls evaluated for MIF polymorphisms, were included. The occurrence of CAD was found to be associated with the C allele of the MIF rs755622 SNP in the total population (C/G, OR = 1.489, 95% CI = 1.223-1.813). Further, MIF -173G/C polymorphism was significantly associated with CAD under the allelic model in the Asian (C/G, OR = 1.775, 95% CI = 1.365-2.309) and Caucasian (C/G, OR = 1.288, 95% CI 1.003-1.654) subgroups. The data showed that the risk of CAD was higher in the population carrying the C allele. CONCLUSIONS: We found evidence of associations between MIF -173C/G and CAD susceptibility in the Asian and Caucasian populations.

Template-Assisted Electrodeposition of Porous Fe-Ni-Co Nanowires with Vigorous Hydrogen Evolution.

A novel method to fabricate porous Fe-Ni-Co nanowires directly by electrodepositing into polycarbonate membranes is reported when the electrolyte pH < 0.5. Hydrogen bubbles are used as a dynamic porous template created by operating in electrolytes with very low pH to drive the proton reduction reaction. The electrolyte pH was adjusted with sulfuric acid, and the added sulfate ions are thought to help reduce bubble coalescence, but not detachment at the electrode surface, to facilitate metal deposition within the nanopores. Porous nanowires were obtained when the electrolyte pH was less than 1.0. The average alloy composition was found to be pH sensitive, which shifted from an Fe-rich porous alloy to a Ni-rich porous alloy as the electrolyte pH decreased.

Impact of different drying processes on the lipid deterioration and color characteristics of Penaeus vannamei.

BACKGROUND: Fresh shrimp (Penaeus vannamei) deteriorates easily and the drying process is an important processing method for prolonging the shelf life of shrimp. The traditional drying method is hot-air-drying (HD), which can cause some problems such as nutrient loss, discoloration and lipid oxidation. In recent years, freeze-drying (FD) has been popular for removing moisture from food at lower temperatures, maintaining the structure of raw materials, and improving storage stability of products. In the present study, the effects of HD and FD on lipid and color of P. vannamei and the mechanisms involved were investigated. RESULTS: FD caused less lipid oxidation compared to HD; consequently, FD-processed shrimps had lower levels of primary and secondary oxidation products, as well as acid value, and higher contents of triacylglycerol, phosphatidylcholine, phosphatidylethanolamine, eicosapentaenoic acid and docosahexaenoic acid compared to HD-processed samples. Lipase and lipoxygenase played a role in the oxidation and hydrolysis of lipids during drying process. FD-processed shrimps had lower yellowness value and chromatic aberrations but a higher whiteness value compared to HD-processed samples. Correlation analysis showed that lipid oxidation, astaxanthin degradation and the Maillard reaction contributed to the changes of color. Principal component analysis indicated that FD caused less deterioration in quality compared to HD. CONCLUSION: In the present study, FD is recommended for preserving shrimp color and lipid nutrition in terms of lipid oxidation control. © 2020 Society of Chemical Industry.

Degradation of Rhodamine B Under Visible-Light by Cu-Doped ZnAl Layered Double Hydroxide.

The Cu-doped ZnAl layered double hydroxides (LDH) were papered by coprecipitation. The prepared samples were characterized by mutiple techniques including X-ray diffraction (XRD), Brunauer-Emmett-Teller (BET) surface area, scanning electronic microscopy (SEM), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS) and UV-vis diffuse-reflectance spectroscopy (UV-vis DRS). The doping of Cu2+ into the LDH sheets results in formation of the distorted CuO6 octahedrons which contribute for the excitation of electrons under visible light. The doped Cu2+ also serves as photo-generated charges separator and improves the visible-light-driven photocatalytic activity of ZnAl LDH. A degradation mechanism based on the hydroxyl radical as the active species was proposed.

Isolation and identification of zinc-chelating peptides from sea cucumber (Stichopus japonicus) protein hydrolysate.

BACKGROUND: Zinc is known to play an essential role in the biological activities in the human body. In this study, a zinc-chelating peptide (ZCP) produced by Alcalase-assisted hydrolysis of the body wall of sea cucumber was isolated and identified. The ZCP was purified stepwise by ultrafiltration, anion-exchange chromatography, and gel filtration chromatography, in conjunction with ultraviolet-visual (UV-visual) spectrophotometry, which was used to analyze each purified fraction. RESULTS: Analysis of the purified ZCP revealed that its zinc-chelating ability was 33.31%. Analysis of isothermal titration calorimetry suggested that the binding of ZCP and zinc (N ≈ 2) was endothermic, with weak binding affinity. Fourier transform infrared spectroscopy spectra (FTIR) indicated that carboxylic and amide groups in ZCP were the primary binding sites of Zn. Sequencing the result by ultra-performance liquid chromatography-quadrupole/time of flight mass spectrometry (UPLC-Q-TOF-MS/MS) showed that a representative ZCP had the sequence WLTPTYPE with a molecular weight of 1005.5 Da. CONCLUSION: These results provide a promising foundation for the production of zinc supplements from sea-cucumber-derived ZCPs. © 2019 Society of Chemical Industry.

Multi-regional sequencing reveals intratumor heterogeneity and positive selection of somatic mtDNA mutations in hepatocellular carcinoma and colorectal cancer.

Recent studies have revealed significant intratumor heterogeneity (ITH) of nuclear genome mutations and highlighted its function in tumor progression and treatment resistance. However, the ITH of somatic mitochondrial DNA (mtDNA) mutations detected in cancers remains unknown. In this study, we performed multiregional mtDNA sequencing of tumor and paratumor tissue samples from 12 hepatocellular carcinoma (HCC) and 13 colorectal cancer (CRC) patients. A substantial level of mtDNA mutations was found in paired non-HCC inflammatory tissues, suggesting that these tissues might not be mtDNA-genetically "normal." Moreover, our data indicated that the ITH of somatic mtDNA mutations was a common feature in HCC and CRC patients. In addition, we found that shared mutations which were observed in at least 2 samples in each patient exhibited a significantly higher heteroplasmic level than mutations that were private to a specific tumor region from both HCC (p = 0.039) and CRC patients (p = 0.001). The heteroplasmic level of shared mutations was positively correlated with intratumoral recurrence of mtDNA mutations. We also found that shared mutations in tumor tissues with a higher degree of pathogenicity risk exhibited a higher heteroplasmic level and intratumoral recurrence in both HCC and CRC patients. These findings suggest that some mtDNA mutations may undergo positive selection during the clonal expansion. Taken together, our analyses identified various levels of ITH of somatic mtDNA mutations in HCC and CRC patients and provided evidence supporting the positive selection working on some somatic mtDNA mutations in tumor tissues.

CD147-CD98hc complex contributes to poor prognosis of non-small cell lung cancer patients through promoting cell proliferation via the PI3K/Akt signaling pathway.

BACKGROUND: It has been reported that CD147 and CD98 heavy chain (CD98hc) form a complex on the cell plasma membrane of several cancers; however, whether this complex exists in non-small cell lung cancer (NSCLC) cells and affects the prognosis of patients remains to be elucidated. METHODS: The expression of CD147 and CD98hc was assessed in tissue samples from 241 NSCLC patients and NSCLC cell lines. The correlation between CD147 and CD98hc expression and their association with the prognosis of NSCLC patients were analyzed. We also evaluated the impact of CD147 and CD98hc on the growth of NSCLC cells as well as Akt phosphorylation. RESULTS: Both CD147 and CD98hc were significantly upregulated in NSCLC cells, and their expression levels were significantly correlated (p < 0.001). Immunoflurenece staining and co-immunoprecipitation demonstrated that CD147 and CD98hc could form a complex on NSCLC cells. Compared with NSCLC patients with CD147-/CD98hc-, those with CD147+/CD98hc+ exhibited a significantly poor overall survival (OS) with a hazard ratio (HR) of 1.92 (p = 0.010), and a significantly increased risk of recurrence with a HR of 1.97 (p = 0.004). Also, we demonstrated that the proliferation of lung cancer cell lines was significantly affected by knockdown and force-expression of the CD147-CD98hc complex. Western blot analysis indicated that the phosphorylation of Akt in NSCLC cells was significantly affected by knockdown and overexpression of either or both CD147 and CD98hc. CONCLUSIONS: Our findings indicate that the CD147-CD98hc complex significantly contributes to poor prognosis of NSCLC patients through promoting cell proliferation via the PI3K/Akt pathway.

Association of leukocyte mitochondrial DNA content with glioma risk: evidence from a Chinese case-control study.

BACKGROUND: Increasing evidence suggests that alterations in mitochondrial DNA (mtDNA) content may be implicated in the tumorigenesis of several malignancies. However, the association between mtDNA content in peripheral blood lymphocytes (PBLs) and glioma risk has not been investigated. METHODS: Real-time PCR was used to examine the mtDNA content in PBLs of 414 glioma patients and 414 matched controls in a hospital-based case-control study. The association between mtDNA content and glioma risk was evaluated using an unconditional multivariate logistic regression model. RESULTS: We found that glioma patients exhibited a significantly higher median mtDNA content than healthy controls (0.99 vs. 0.71, P < 0.001). Unconditional multivariate logistic regression analysis adjusting for age, gender, smoking status, and family cancer history showed that there was an S-shaped association between mtDNA content and glioma risk. Higher mtDNA content was significantly associated with an elevated risk of glioma. Compared with the first quartile, the odds ratio (95% confidence interval) for subjects in the second, third, and fourth quartiles of mtDNA content were 0.90 (0.52-1.53), 3.38 (2.15-5.31), and 5.81 (3.74-9.03), respectively (P for nonlinearity = 0.009). Stratified analysis showed that the association between mtDNA content and glioma risk was not modulated by major host characteristics. CONCLUSIONS: Our findings demonstrate for the first time that a higher mtDNA content in PBLs is associated with an elevated risk of glioma, which warrants further investigation in larger populations.

Apak competes with p53 for direct binding to intron 1 of p53AIP1 to regulate apoptosis.

The KRAB-type zinc-finger protein Apak was recently identified as a negative regulator of p53-mediated apoptosis. However, the mechanism of this selective regulation is not fully understood. Here, we show that Apak recognizes the TCTTN2−30TTGT consensus sequence through its zinc-fingers. This sequence is specifically found in intron 1 of the proapoptotic p53 target gene p53AIP1 and largely overlaps with the p53-binding sequence. Apak competes with p53 for binding to this site to inhibit p53AIP1 expression. Upon DNA damage, Apak dissociates from the DNA, which abolishes its inhibitory effect on p53-mediated apoptosis.

Effects of Edible Organic Acid Soaking on Color, Protein Physicochemical, and Digestion Characteristics of Ready-to-Eat Shrimp upon Processing and Sterilization.

Soft-packed ready-to-eat (RTE) shrimp has gradually become popular with consumers due to its portability and deliciousness. However, the browning caused by high-temperature sterilization is a non-negligible disadvantage affecting sensory quality. RTE shrimp is processed through "boiling + vacuum soft packing + high temperature and pressure sterilization". Ultraviolet-visible (UV) spectroscopy with CIELAB color measurement showed that phytic acid (PA) + lactic acid (LA), PA + citric acid (CA), and PA + LA + CA soaking before cooking alleviated browning, as well as UVabsorbance and the browning index (BI). Meanwhile, UV spectroscopy and fluorescence spectroscopy showed that organic acid soaking reduced the content of carbonyl, dityrosine, disulfide bonds, surface hydrophobicity, and protein solubility, but promoted the content of free sulfhydryl and protein aggregation. However, in vitro digestion simulations showed that organic acid soaking unexpectedly inhibited the degree of hydrolysis and protein digestibility. This study provides the basis for the application of organic acids as color protectors for RTE aquatic muscle product.