Moisturizing and aroma-enhancing effects of low molecular weight fenugreek polysaccharides in cigarettes.

Polysaccharides possess excellent moisturizing effects due to their abundance of hydrophilic groups and film-forming properties. Additionally, they can produce a refreshing aroma during the pyrolysis process. However, there is scarce research on their application in the tobacco field. Herein, we investigated the effects of low molecular weight fenugreek polysaccharide (FP) obtained through ethanol fractionation and DEAE-52 cellulose column chromatography on moisture retention and aroma enhancement in tobacco. The moisture retention test revealed that the addition of FP increased the moisture retention index (MRI) of tobacco by 11.72 %-16.69 %, indicating that the hydrophilic nature of polysaccharides facilitated the migration of free water in tobacco to bound water, resulting in reduced water activity. Moreover, the contact angle between polysaccharide and tobacco was <90°, enabling better infiltration into tobacco and slowing down tobacco shrinkage caused by water loss. Among all the components, EFP-20 and EFP-40 demonstrated superior performance. Furthermore, FP exhibited excellent thermal stability below 200 °C and can decomposed to produce aromatic substances at high temperatures. It also demonstrated the ability to adsorb ethyl heptanoate and thermally decompose to produce a substantial amount of heptanoic acid. Consequently, the incorporation of FP in tobacco demonstrated favorable effects on both moisturization and aroma enhancement.

CD147: an integral and potential molecule to abrogate hallmarks of cancer.

CD147 also known as EMMPRIN, basigin, and HAb18G, is a single-chain type I transmembrane protein shown to be overexpressed in aggressive human cancers of CNS, head and neck, breasts, lungs, gastrointestinal, genitourinary, skin, hematological, and musculoskeletal. In these malignancies, the molecule is integral to the diverse but complimentary hallmarks of cancer: it is pivotal in cancerous proliferative signaling, growth propagation, cellular survival, replicative immortality, angiogenesis, metabolic reprogramming, immune evasion, invasion, and metastasis. CD147 also has regulatory functions in cancer-enabling characteristics such as DNA damage response (DDR) and immune evasion. These neoplastic functions of CD147 are executed through numerous and sometimes overlapping molecular pathways: it transduces signals from upstream molecules or ligands such as cyclophilin A (CyPA), CD98, and S100A9; activates a repertoire of downstream molecules and pathways including matrix metalloproteinases (MMPs)-2,3,9, hypoxia-inducible factors (HIF)-1/2α, PI3K/Akt/mTOR/HIF-1α, and ATM/ATR/p53; and also functions as an indispensable chaperone or regulator to monocarboxylate, fatty acid, and amino acid transporters. Interestingly, induced loss of functions to CD147 prevents and reverses the acquired hallmarks of cancer in neoplastic diseases. Silencing of Cd147 also alleviates known resistance to chemoradiotherapy exhibited by malignant tumors like carcinomas of the breast, lung, pancreas, liver, gastric, colon, ovary, cervix, prostate, urinary bladder, glioblastoma, and melanoma. Targeting CD147 antigen in chimeric and induced-chimeric antigen T cell or antibody therapies is also shown to be safer and more effective. Moreover, incorporating anti-CD147 monoclonal antibodies in chemoradiotherapy, oncolytic viral therapy, and oncolytic virus-based-gene therapies increases effectiveness and reduces on and off-target toxicity. This study advocates the expedition and expansion by further exploiting the evidence acquired from the experimental studies that modulate CD147 functions in hallmarks of cancer and cancer-enabling features and strive to translate them into clinical practice to alleviate the emergency and propagation of cancer, as well as the associated clinical and social consequences.

Enhancing cord blood stem cell-derived NK cell growth and differentiation through hyperosmosis.

BACKGROUND: Natural killer (NK) cells hold great promise in treating diverse hematopoietic and solid tumors. Despite their availability from peripheral blood and cord blood, stem cell-derived NK cells offer an 'off-the-shelf' solution. Hematopoietic stem and progenitor cells (HSPCs) derived from cord blood pose no risk to the newborn or mother and are virtually ideal sources for NK cell differentiation. METHODS: We developed a modified protocol to differentiate HSPCs to NK cells under serum-free conditions using defined factors. The HSPC-derived NK (HSC-NK) cells could be expanded in a K562 feeder cell-dependent manner. Furthermore, using lentivirus transduction, chimeric antigen receptor (CAR)-modified HSPCs could be differentiated into NK cells, leading to the establishment of CAR-NK cells. RESULTS: The efficiency of NK cell differentiation from HSPCs was increased through the simple modulation of osmotic pressure by the addition of sodium chloride or glucose. Furthermore, the hyperosmosis-primed HSC-NK cells exhibited enhanced proliferation capacity and maintained normal functional characteristics, including transcriptome and antitumor efficacy. The optimized protocol yielded approximately 1.8 million NK cells from a single CD34-positive cell within a 28-day cycle, which signifies more than a ten-fold increase in efficiency relative to the conventional methods. This optimized protocol was also suitable for generating CAR-NK cells with high yields compared to standard conditions. CONCLUSIONS: The results of this study establish high osmotic pressure as a simple yet powerful adjustment that significantly enhances the efficiency and functionality of HSC-NK cells, including CAR-NK cells. This optimized protocol could lead to cost-effective, high-yield NK cell therapies, potentially revolutionizing cancer immunotherapy strategies.

Psychoneurological symptoms and inflammatory markers in patients with glioma in China: a network analysis.

PURPOSE: Anxiety, depression, sleep disorder, fatigue, and pain develop as common psychoneurological symptoms in patients with glioma, and their occurrence and development are potentially related to inflammatory factors. However, this theory has not been proven within the context of glioma. This study aimed to estimate interconnections among psychoneurological symptoms and inflammatory biomarkers by a network analysis. PATIENTS AND METHODS: We selected 203 patients with stage I-IV glioma from a tertiary hospital in China using convenient sampling method. Patients completed the self-made questionnaires, Hamilton Anxiety Scale-14 (HAMA-14), Hamilton Depression Scale-24 (HAMD-24), Pittsburgh Sleep Quality Index (PSQI), Multidimensional Fatigue Inventory-20 (MFI-20), and pain Numerical Rating Scale (NRS). The plasma inflammatory cytokines were examined. Partial correlation network analysis was performed to illustrate interactions of symptoms and inflammatory biomarkers. RESULTS: Among the 203 included patients, all psychoneurological symptoms, except for depression and pain, exhibited significant connections with each other. Depression, anxiety, fatigue, interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) with higher strength centrality indices were identified as the most central node within the symptom-biomarker network. CONCLUSIONS: Depression, anxiety, fatigue, IL-6, and TNF-α play a significant role in the symptom-biomarker network in patients with glioma. Medical staff should strengthen the dynamic evaluation of the involved symptoms and inflammatory cytokines and take effective measures to alleviate the burden of symptoms and improve the quality of life of patients.

N-acetylcysteine alleviates oxidative stress and apoptosis and prevents skeletal muscle atrophy in type 1 diabetes mellitus through the NRF2/HO-1 pathway.

AIMS: Type 1 diabetes mellitus (T1DM) has been linked to the occurrence of skeletal muscle atrophy. Insulin monotherapy may lead to excessive blood glucose fluctuations. N-acetylcysteine (NAC), a clinically employed antioxidant, possesses cytoprotective, anti-inflammatory, and antioxidant properties. The objective of our study was to evaluate the viability of NAC as a supplementary treatment for T1DM, specifically regarding its therapeutic and preventative impacts on skeletal muscle. MAIN METHODS: Here, we used beagles as T1DM model for 120d to explore the mechanism of NRF2/HO-1-mediated skeletal muscle oxidative stress and apoptosis and the therapeutic effects of NAC. Oxidative stress and apoptosis related factors were analyzed by immunohistochemistry, immunofluorescence, western blotting, and RT-qPCR assay. KEY FINDINGS: The findings indicated that the co-administration of NAC and insulin led to a reduction in creatine kinase levels, preventing weight loss and skeletal muscle atrophy. Improvement in the reduction of muscle fiber cross-sectional area. The expression of Atrogin-1, MuRF-1 and MyoD1 was downregulated, while Myh2 and MyoG were upregulated. In addition, CAT and GSH-Px levels were increased, MDA levels were decreased, and redox was maintained at a steady state. The decreased of key factors in the NRF2/HO-1 pathway, including NRF2, HO-1, NQO1, and SOD1, while KEAP1 increased. In addition, the apoptosis key factors Caspase-3, Bax, and Bak1 were found to be downregulated, while Bcl-2, Bcl-2/Bax, and CytC were upregulated. SIGNIFICANCE: Our findings demonstrated that NAC and insulin mitigate oxidative stress and apoptosis in T1DM skeletal muscle and prevent skeletal muscle atrophy by activating the NRF2/HO-1 pathway.

Biocatalytic Fluoroalkylation Using Fluorinated S-Adenosyl-l-methionine Cofactors.

Modification of organic molecules with fluorine functionalities offers a critical approach to develop new pharmaceuticals. Here, we report a multienzyme strategy for biocatalytic fluoroalkylation using S-adenosyl-l-methionine (SAM)-dependent methyltransferases (MTs) and fluorinated SAM cofactors prepared from ATP and fluorinated l-methionine analogues by an engineered human methionine adenosyltransferase hMAT2AI322A. This work introduces the first example of biocatalytic 3,3-difluoroallylation. Importantly, this strategy can be applied to late-stage site-selective fluoroalkylation of complex molecule vancomycin with conversions up to 99%.

Sequential targeting biomimetic nano platform for enhanced mild photothermal therapy and chemotherapy of tumor.

Tumor targeting drug delivery is of significant importance for the treatment of triple negative breast cancer (TNBC) considering the presence of appreciable amount of tumor matrix and the absence of effective targets on the tumor cells. Hence in this study, a new therapeutic multifunctional nanoplatform with improved TNBC targeting ability and efficacy was constructed and used for therapy of TNBC. Specifically, curcumin loaded mesoporous polydopamine (mPDA/Cur) nanoparticles were synthesized. Thereafter, manganese dioxide (MnO2) and a hybrid of cancer-associated fibroblasts (CAFs) membranes as well as cancer cell membranes were sequentially coated on the surface of mPDA/Cur to obtain mPDA/Cur@M/CM. It was found that two distinct kinds of cell membranes were able to endow the nano platform with homologous targeting ability, thereby achieving accurate delivery of drugs. Nanoparticles gathered in the tumor matrix can loosen the tumor matrix via the photothermal effect mediated by mPDA to rupture the physical barrier of tumor, which is conducive to the penetration and targeting of drugs to tumor cells in the deep tissues. Moreover, the existence of curcumin, MnO2 and mPDA was able to promote the apoptosis of cancer cells by promoting increased cytotoxicity, enhanced Fenton-like reaction, and thermal damage, respectively. Overall, both in vitro and in vivo results showed that the designed biomimetic nanoplatform could significantly inhibit the tumor growth and thus provide an efficient novel therapeutic strategy for TNBC.

N-acetyl-L-cysteine alleviates FUNDC1-mediated mitophagy by regulating mitochondrial dynamics in type 1 diabetic nephropathy canine.

Diabetic nephropathy (DN) is a major complication of type 1 diabetes mellitus, and hyperglycemia and hypertension are the main risk factors for the development of DN. N-Acetyl-Cysteine (NAC) has a variety of effects, interfering with the production and scavenging of free radicals and regulating the metabolic activity of tissue cells. However, the efficacy of NAC on DN treatment is unclear. Thus, this study investigated the protective mechanism of NAC combined with insulin on renal injury in dogs with DN. The forty dogs were selected and divided into control group, DM group, INS group, INS + NAC group and NAC group to establish the model for a trial period of 4 months. The results revealed that INS + NAC was effective in reducing and stabilizing blood glucose levels. Biochemical results showed that INS + NAC treatment significantly regulated the stability of UREA, CREA and fructosamine indicators. Meanwhile, histopathology staining showed significant glomerular wrinkling and fibrosis in the DM group, which could be reversed after INS + NAC treatment. In addition, INS + NAC could restore mitochondria homeostasis by upregulating the levels of mitochondrial fission (MFN1, MFN2 and OPA1) and inhibiting of mitochondrial fusion (DRP1, FIS1 and MFF) related indicators. Further studies revealed that INS + NAC regulated the expression levels of renal BNIP3, NIX and FUNDC1 in the DM group, thereby alleviating mitophagy. Collectively, these results suggested that NAC combined with insulin protects DN by regulating the mitochondrial dynamics and FUNDC1-mediated mitophagy.

MRI-based radiomics analysis for preoperative evaluation of lymph node metastasis in hypopharyngeal squamous cell carcinoma.

Objective: To investigate the role of pre-treatment magnetic resonance imaging (MRI) radiomics for the preoperative prediction of lymph node (LN) metastasis in patients with hypopharyngeal squamous cell carcinoma (HPSCC). Methods: A total of 155 patients with HPSCC were eligibly enrolled from single institution. Radiomics features were extracted from contrast-enhanced axial T-1 weighted (CE-T1WI) sequence. The most relevant features of LN metastasis were selected by the least absolute shrinkage and selection operator (LASSO) method. Univariate and multivariate logistic regression analysis was adopted to determine the independent clinical risk factors. Three models were constructed to predict the LN metastasis status: one using radiomics only, one using clinical factors only, and the other one combined radiomics and clinical factors. Receiver operating characteristic (ROC) curves and calibration curve were used to evaluate the discrimination and the accuracy of the models, respectively. The performances were tested by an internal validation cohort (n=47). The clinical utility of the models was assessed by decision curve analysis. Results: The nomogram consisted of radiomics scores and the MRI-reported LN status showed satisfactory discrimination in the training and validation cohorts with AUCs of 0.906 (95% CI, 0.840 to 0.972) and 0.853 (95% CI, 0.739 to 0.966), respectively. The nomogram, i.e., the combined model, outperformed the radiomics and MRI-reported LN status in both discrimination and clinical usefulness. Conclusions: The MRI-based radiomics nomogram holds promise for individual and non-invasive prediction of LN metastasis in patients with HPSCC.

Palbociclib Induces the Apoptosis of Lung Squamous Cell Carcinoma Cells via RB-Independent STAT3 Phosphorylation.

Lung squamous cell carcinoma (LUSC) treatment response is poor and treatment alternatives are limited. Palbociclib, a cyclin-dependent kinase (CDK) 4/6 inhibitor, has recently been approved for hormone receptor-positive breast cancer patients and applied in multiple preclinical models, but its use for LUSC therapy remains elusive. Here, we investigated whether palbociclib induced cell apoptosis and dissected the underlying mechanism in LUSC. We found that palbociclib induced LUSC cell apoptosis through inhibition of Src tyrosine kinase/signal transducers and activators of transcription 3 (STAT3). Interestingly, palbociclib reduced STAT3 signaling in LUSC cells interfered by retinoblastoma tumor-suppressor gene (RB), suggesting that pro-apoptosis effect of palbociclib was independent of classic CDK4/6-RB signaling. Furthermore, palbociclib could suppress IL-1ß and IL-6 expression, and therefore blocked Src/STAT3 signaling, which were rescued by either recombinant human IL-1ß or IL-6. Moreover, Myc mediated the sensitivity of LUSC cells to palbociclib. Our discoveries demonstrated that palbociclib induces apoptosis of LUSC cells through the Src/STAT3 axis in an RB-independent manner, and provided a reliable experimental basis of clinical studies in LUSC patients.

Characterization of stem cell landscape and identification of stemness-relevant prognostic gene signature to aid immunotherapy in colorectal cancer.

BACKGROUND: It is generally accepted that colorectal cancer (CRC) originates from cancer stem cells (CSCs), which are responsible for CRC progression, metastasis and therapy resistance. The high heterogeneity of CSCs has precluded clinical application of CSC-targeting therapy. Here, we aimed to characterize the stemness landscapes and screen for certain patients more responsive to immunotherapy. METHODS: Twenty-six stem cell gene sets were acquired from StemChecker database. Consensus clustering algorithm was applied for stemness subtypes identification on 1,467 CRC samples from TCGA and GEO databases. The differences in prognosis, tumor microenvironment (TME) components, therapy responses were evaluated among subtypes. Then, the stemness-risk model was constructed by weighted gene correlation network analysis (WGCNA), Cox regression and random survival forest analyses, and the most important marker was experimentally verified. RESULTS: Based on single-sample gene set enrichment analysis (ssGSEA) enrichments scores, CRC patients were classified into three subtypes (C1, C2 and C3). C3 subtype exhibited the worst prognosis, highest macrophages M0 and M2 infiltrations, immune and stromal scores, and minimum sensitivity to immunotherapies, but was more sensitive to drugs like Bosutinib, Docetaxel, Elesclomol, Gefitinib, Lenalidomide, Methotrexate and Sunitinib. The turquoise module was identified by WGCNA that it was most positively correlated with C3 but most negatively with C2, and five hub genes in turquoise module were identified for stemness model construction. CRC patients with higher stemness scores exhibited worse prognosis, more immunosuppressive components in TME and lower immunotherapeutic responses. Additionally, the model's immunotherapeutic prediction efficacy was further confirmed from two immunotherapy cohorts (anti-PD-L1 in IMvigor210 cohort and anti-PD-1 in GSE78220 cohort). Mechanistically, Gene Set Enrichment Analysis (GSEA) results revealed high stemness score group was enriched in interferon gamma response, interferon alpha response, P53 pathway, coagulation, apoptosis, KRAS signaling upregulation, complement, epithelial-mesenchymal transition (EMT) and IL6-mediated JAK-STAT signaling gene sets. CONCLUSIONS: Our study characterized three stemness-related subtypes with distinct prognosis and TME patterns in CRC patients, and a 5-gene stemness-risk model was constructed by comprehensive bioinformatic analyses. We suggest our stemness model has prospective clinical implications for prognosis evaluation and might facilitate physicians selecting prospective responders for preferential use of current immune checkpoint inhibitors.

Blood Inflammatory Cytokines as Predictors of Depression in Patients With Glioma.

Background: Depression commonly develops as a comorbid disorder related to glioma, which affects the patients' physical function and prognosis. Circulating inflammatory cytokines are potential predictors of depression in disparate cancers. However, less research has specifically investigated this aspect within the context of glioma. Study objectives: The objective of this study was to investigate the occurrence of depression in patients with glioma and draw a comparison of the ability to predict it through diverse inflammatory cytokines. Methods: A total of 203 patients with stage I-IV glioma were enrolled in this study. Depression was evaluated according to the Hamilton Depression Scale, and the plasma inflammatory cytokines levels were simultaneously measured. We performed the receiver operating characteristic (ROC) analysis to confirm the abilities of identified inflammatory cytokines to predict depression. Results: Among the 203 patients with glioma, 135 (66.5%) showed obvious depressive symptoms. Proinflammatory cytokines, including interleukin (IL)-6 (area under the curve (AUC) = 0.76) and tumor necrosis factor (TNF)-α (AUC = 0.75), showed good performance in accurately predicting depression in patients with glioma. These inflammatory cytokines indicated great potential to be depression biomarkers regardless of the patients' disparate treatment experience. Conclusion: With their relatively simple and time-saving measurement procedures, inflammatory cytokines should be seriously considered effective clinical screening and diagnostic tools, as well as potential biomarkers for depression in patients with glioma.

The prognostic value of the preoperative inflammatory index on the survival of glioblastoma patients.

OBJECTIVES: The growth and development of tumors are closely related to the initiation and amplification of the inflammatory response. Various inflammatory biomarkers had attained growing attention for nearly two decades and were discovered strongly associated with cancer patients' prognosis, indicating that systemic inflammatory response is possibly essential to cancer progression. However, little was known about the sensitive biomarkers associated with the detection, persistence, treatment, and prognosis of GBM. Hence, the retrospective research endeavored to evaluate the prognostic value of preoperative inflammatory biomarkers in patients with GBM who initially received standardized treatment. METHODS: The 232 glioblastoma patients eligible who were admitted to Qilu Hospitals in Shandong Province from January 2014 to January 2018 were collected for this analysis. Inflammatory markers, including the systemic immune-inflammation index (SII), systemic immune response index (SIRI), neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), monocyte-lymphocyte ratio (MLR), and albumin/globulin ratio (AGR), were designed. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method, and we calculated the area under the ROC curve to determine the AUC value. Besides, we used the Cox proportional hazard model to estimate the relationship between variables and PFS and OS. The statistical differences between variables and PFS and OS were tested through the log-rank test. What is more, the LR method was used to perform Cox multiple regression analysis. The results were represented by hazard ratio (HR), 95% CI, any 2-tailed P < 0.01 was accepted as statistically different. RESULTS: The multivariate Cox proportional hazard model presented that SII ≥ 659.1 was an independent risk factor affecting OS (HR = 2.238, 95% CI = 1.471-3.406, P < 0.001) and postoperative PFS (HR = 2.000, 95% CI = 1.472-2.716, P < 0.001) in GBM patients. The 1-, 3-, and 5-year OS of the SII < 659.1 group was 70.8%, 26.9%, and 14.1%, respectively, while the 1- and 3-year OS of the SII ≥ 659.1 group was 37.5% and 11.5% (P < 0.001). The 1-, 3-, and 5-year PFS of the SII < 659.1 group was 36.3%, 19.6%, and 13%, respectively, while the 1-year PFS of the SII ≥ 659.1 group was 11.3% (P < 0.001). Results of patients' clinical and pathological characteristics paraded that in comparison to the lower SII group, the higher SII group had significantly inferior Karnofsky Performance Scale (KPS) scores (P < 0.001) and more frequent cystic changes of the tumors (P < 0.001), whereas the values of SIRI, NLR, PLR, MLR, and AGR were low. CONCLUSIONS: SII is an independent inflammatory indicator for predicting the prognosis of GBM patients after receiving initially standardized treatments.

Weighted Gene Co-expression Network Analysis Identifies a Cancer-Associated Fibroblast Signature for Predicting Prognosis and Therapeutic Responses in Gastric Cancer.

Background: Cancer-associated fibroblasts (CAFs) are the most prominent cellular components in gastric cancer (GC) stroma that contribute to GC progression, treatment resistance, and immunosuppression. This study aimed at exploring stromal CAF-related factors and developing a CAF-related classifier for predicting prognosis and therapeutic effects in GC. Methods: We downloaded mRNA expression and clinical information of 431 GC samples from Gene Expression Omnibus (GEO) and 330 GC samples from The Cancer Genome Atlas (TCGA) databases. CAF infiltrations were quantified by the estimate the proportion of immune and cancer cells (EPIC) method, and stromal scores were calculated via the Estimation of STromal and Immune cells in MAlignant Tumors using Expression data (ESTIMATE) algorithm. Stromal CAF-related genes were identified by weighted gene co-expression network analysis (WGCNA). A CAF risk signature was then developed using the univariate and least absolute shrinkage and selection operator method (LASSO) Cox regression model. We applied the Spearman test to determine the correlation among CAF risk score, CAF markers, and CAF infiltrations (estimated via EPIC, xCell, microenvironment cell populations-counter (MCP-counter), and Tumor Immune Dysfunction and Exclusion (TIDE) algorithms). The TIDE algorithm was further used to assess immunotherapy response. Gene set enrichment analysis (GSEA) was applied to clarify the molecular mechanisms. Results: The 4-gene (COL8A1, SPOCK1, AEBP1, and TIMP2) prognostic CAF model was constructed. GC patients were classified into high- and low-CAF-risk groups in accordance with their median CAF risk score, and patients in the high-CAF-risk group had significant worse prognosis. Spearman correlation analyses revealed the CAF risk score was strongly and positively correlated with stromal and CAF infiltrations, and the four model genes also exhibited positive correlations with CAF markers. Furthermore, TIDE analysis revealed high-CAF-risk patients were less likely to respond to immunotherapy. GSEA revealed that epithelial-mesenchymal transition (EMT), TGF-ß signaling, hypoxia, and angiogenesis gene sets were significantly enriched in high-CAF-risk group patients. Conclusion: The present four-gene prognostic CAF signature was not only reliable for predicting prognosis but also competent to estimate clinical immunotherapy response for GC patients, which might provide significant clinical implications for guiding tailored anti-CAF therapy in combination with immunotherapy for GC patients.

Biocatalyst and colorimetric biosensor of carcinoembryonic antigen constructed via chicken egg white-copper phosphate organic/inorganic hybrid nanoflowers.

In this article, the dual-functional chicken egg white-copper phosphate organic-inorganic hybrid nanoflowers (Cu-NFs), combining the functions of signal amplification and biological recognition, were prepared through a simple one-pot method. The Cu-NFs exhibit excellent biocatalytic activity of peroxidase and polyphenol oxidase. Besides, a biotin-labeled secondary antibody encapsulated Cu-NFs-2 (Cu-NFs-2@Biotin-NHS-Ab2) capture probe was prepared by using the interaction between avidin in the egg white and biotin. Based upon this superiority, the as-prepared Cu-NFs-2 were used in labeled avidin-biotin enzyme-linked immunosorbent assay (Cu-NFs-2 based-LAB-ELISA) to construct a sensitive colorimetric biosensor for the ultrasensitive detection of carcinoembryonic antigen (CEA). Under weak alkaline (pH = 7.5) conditions, the as-developed colorimetric sensor displayed a wide linear range of 0.05-40 ng/mL with a detection limit of 3.52 pg/mL. Furthermore, this colorimetric sensor has been successfully applied to the detection of CEA in human serum samples. Therefore, the as-developed colorimetric sensor has broad application prospects in the field of medical diagnosis and portable detection.

Immune persistence induced by three doses of 60 µg hepatitis B vaccine in non-responders following standard primary vaccination in Chinese adults.

This study consisted of two rounds of cross-sectional observations designed to evaluate the persistence of immune protection induced high antigen content hepatitis B (HB) vaccine at 60 µg/1.0 ml formulations administered at a three-dose schedule (Days 0, 28, and 56) in non-responders to routine HB vaccination. In the original phase 3 study, we enrolled 1091 healthy participants (16-60 years old) seronegative for antibody against HB surface antigen (anti-HBs) after primary vaccination. Participants were randomized (2:2:1) to receive three booster doses of HB vaccine containing 60 µg, 30 µg, or 10 µg of antigen per dose 28 days apart. In the group receiving the 60 µg HB vaccine, 428 participants' serum samples were available at pre-vaccination and 28 days after each vaccine dose and were included in immunogenicity analysis. With two written informed consents, we collected blood samples from 276 (67.2%) participants in 2014 and 239 (58.2%) in 2019, who had completed the full course of revaccination and reached the seropositive (anti-HBs≥10 mIU/ml) standard in the 60 µg vaccine group of the original phase 3 study. The HBV seropositive rate was found to decrease from 96.0% in 28 days after receiving the third dose of 60 µg HB vaccine, to 48.2% in 2014, and to 40.6% in 2019, with anti-HBs GMC of seropositive individuals was 584.0 mIU/ml, 142.4 mIU/ml, and 169.1 mIU/ml, respectively. Analysis of 181 vaccinees who had serologic test results available both in 2014 and in 2019, and results revealed a dynamic trend in anti-HBs titer similar to that for the whole immune persistence cohort. Of paramount importance, the serologic test results found that 24.9% (45/181) participants had higher anti-HBs concentrations in 2019 than in 2014, this could be interpreted as natural boosters, secondary to HBV exposure without infection because protected. In conclusion, protective antibody persists about 11 years after immunization of Chinese non-responders with 3 doses of 60 µg HB vaccine. Booster doses of vaccine do not seem necessary to ensure long-term protection.

The application of glycine betaine to alleviate the inhibitory effect of salinity on one-stage partial nitritation/anammox process.

One-stage partial nitritation/anammox (PN/A) has been proposed as a sustainable method for removing nitrogen from various wastewater. However, the activities of ammonium-oxidizing bacteria (AOB) and anammox bacteria are often inhibited by the exposure to salinity, thereby hindering their wide application in treating industrial wastewater with high salinity. This study reports that the addition of glycine betaine (GB), which is a compatible solute, could alleviate the inhibitory effects of salinity on both AOB and anammox, thereby improving nitrogen removal performance in a one-stage PN/A system. Short-term tests showed that with an addition of GB higher than 1 mM, the activity of AOB and anammox under salinity of 30 g/L could be increased by at least 45% and 51%, respectively. The half-inhibitory concentration of AOB and anammox rose with increasing GB concentration, with 1 mM GB being the optimal cost-effective dosage. Long-term experiments also demonstrated that 1 mM GB addition could enhance nitrogen removal performance and shorten recovery time by 42.9% under a salinity stress of 30 g/L. Collectively, GB addition was found to be a feasible and effective strategy to the counteract adverse effects of salinity on PN/A process. PRACTITIONER POINTS: Glycine betaine (GB) could improving performance of the PN/A process by alleviating the inhibitory effects of salinity on both AOB and anammox bacteria. A GB concentration of 1 mM was found to be optimum in terms of effectiveness and cost. GB addition was a feasible and effective strategy to remain stabilized in the community structure of PN/A sludge. GB could optimize the nitrogen removal performance and shorten the recovery time of PN/A process under saline stress.

Modeling of completely autotrophic nitrogen removal process with salt and glycine betaine addition.

The susceptibility of the completely autotrophic nitrogen removal over nitrite (CANON) process to high salinity limits its widespread application. The addition of glycine betaine (GB), a type of compatible solutes that could resist osmotic stress, could be an effective strategy to enhance the salt tolerance ability of aerobic and anaerobic ammonium oxidizing bacteria (AOB and anammox bacteria) involved in the CANON process. This study aims to make use of mathematical modeling to systematically investigate the effects of salt and GB addition on the activities of AOB and anammox bacteria and the treatment performance of the CANON process. To this end, a series of dedicated batch tests and long-term experiments for the CANON process with salt and GB additions were conducted and the data was used to calibrate and validate the model established to consider the relationships between salt and GB concentrations and bacterial growth in the CANON process. The calibrated/validated CANON process model was then applied to simulate the long-term impacts of GB addition concentration and sludge retention time (SRT) on the CANON process. The results showed that 1 mM GB addition and a SRT of 50 days would be sufficient to protect AOB and anammox bacteria under the high salinity (30 g/L NaCl) conditions studied and therefore reduce the time needed to recover the treatment performance of the CANON process from exposure to salt inhibition by 35%-40%.

Effects of different concentrations of desflurane on the index of cardiac electrophysiological balance in gynecologic surgery patients.

The objectives were to observe the effects of different concentrations of desflurane on QT, QTc, Tp-e, Tp-e/QT, and the index of cardiac electrophysiological balance (iCEB). Sixty patients were randomly divided into group D1, group D2, and group D3 by using a random number table, 20 in each group. After entering the operating room, patients received 10 mL/kg hydroxyethyl starch, 0.1 mg/kg midazolam, 0.1 mg/kg vecuronium, 3 µg/kg fentanyl, and 0.3 mg/kg etomidate intravenously and then accepted intubation and mechanical ventilation. The desflurane evaporator was opened. The concentrations of desflurane in the D1, D2, and D3 groups were maintained at 0.6, 1.3, and 2.0 minimum alveolar concentration (MAC), respectively. Twelve-lead ECGs were recorded at time before induction (T1) and at 20 min after desflurane reached the required concentration (T2). HR and MAP were recorded measure and the QT interval, QTc interval, Tp-e interval, Tp-e/QT ratio, and iCEB were calculated. Compared with before inhalation (T1), the QTc interval was prolonged in the D1, D2, and D3 groups after inhalation of different concentrations of desflurane for 20 min (T2) (P < 0.05) and the Tp-e/QT ratio decreased in the D1 and D2 groups at T2 (P < 0.05). Compared with the D1 and D2 groups, the Tp-e/QT ratio of the D3 group increased at T2 (P < 0.05). There was no significant difference in Tp-e interval and iCEB at any time (P > 0.05). The study suggested that inhalation of desflurane at a normal concentration cannot cause arrhythmogenic characteristics and affect the cardiac electrophysiological stability.

[Value of multi-detector row CT and magnetic resonance imaging in the diagnosis of retinal detachment].

OBJECTIVE: To summarize multi-detector row CT (MDCT) and magnetic resonance imaging (MRI) features of retinal detachment and evaluate the diagnostic value of these two imaging modalities. METHODS: The MDCT and MRI manifestations were reviewed in 45 cases (47 eyes) of retinal detachment, among which 16 cases (17 eyes) were examined by MDCT and 29 cases (30 eyes) by MRI. Thirty-two cases (33 eyes) were confirmed by operation, and the other 13 cases (14 eyes) were confirmed based on the clinical findings. RESULTS: MDCT and MRI displayed signs of fluid retention between the detached retina and the posterior wall of the eyeball in the cases. Among all these cases, 21 eyes showed simple retinal detachment and 26 had also other pathologies (hemorrhage in 20 eyes and calcification in 6 eyes). Choroidal osteoma was identified in 3 eyes and melanoma of choroid in 5 eyes. CONCLUSION: MDCT is sensitive in detecting calcification in the eyes and MRI with a minimal risk of radiation, and shows advantages in displaying hemorrhage and confined retinal detachment. Both MDCT and MR have high clinical value in the diagnosis of retinal detachment, and their choice depends on the individual condition of the patients.