Molecular and Dissociative Adsorbed Water Concentration and Surface Protonic Conduction in Nanocrystalline TiO2.

Surface protonic conduction in porous nanocrystalline oxides is commonly involved in catalytic processes. The configuration of surface adsorbed water on oxides plays a crucial role in surface protonic conduction. However, studies on the impact of complex surface adsorbed water configuration on the surface water concentration and diffusivity remain limited, and hinder an in-depth understanding of surface proton transport mechanisms, and the design of better surface proton conductors. Here, in situ Raman spectroscopy is utilized to quantitatively identify the contribution of dissociative and molecular adsorbed water components on porous nanocrystalline TiO2 surfaces between 25 and 200 °C. The variations in molecular and dissociative adsorbed water concentration agree with the predominant surface proton conduction mechanisms at three different temperature stages. From 40 to 125 °C, the reduced coverage of molecular adsorbed water layer results in the decreasing proton diffusivity. Water dissociation on the nanocrystalline TiO2 surface is easier in wet N2 than in wet O2, resulting in higher proton conductivity in wet N2; while the surface proton diffusivities in these two atmospheres are similar. The in situ spectroscopy technique enables the improvement of surface proton conducting oxides through quantitative evaluation and modulation of the surface proton concentration and diffusivity.

Hybrid architecture based intelligent diagnosis assistant for GP.

As the first point of contact for patients, General Practitioners (GPs) play a crucial role in the National Health Service (NHS). An accurate primary diagnosis from the GP can alleviate the burden on specialists and reduce the time needed to re-confirm the patient's condition, allowing for more efficient further examinations. However, GPs have broad but less specialized knowledge, which limits the accuracy of their diagnosis. Therefore, it is imperative to introduce an intelligent system to assist GPs in making decisions. This paper introduces two data augmentation methods, the Complaint Symptoms Integration Method and Symptom Dot Separating Method, to integrate essential information into the Integration dataset. Additionally, it proposes a hybrid architecture that fuses the features of words from different representation spaces. Experiments demonstrate that, compared to commonly used pre-trained attention-based models, our hybrid architecture delivers the best classification performance for four common neurological diseases on the enhanced Integration dataset. For example, the classification accuracy of the BERT+CNN hybrid architecture is 0.897, which is a 5.1% improvement over both BERT and CNN with 0.846. Finally, this paper develops an AI diagnosis assistant web application that leverages the superior performance of this architecture to help GPs complete primary diagnosis efficiently and accurately.

Frequency-Stable Robust Wireless Power Transfer Based on High-Order Pseudo-Hermitian Physics.

Nonradiative wireless power transfer (WPT) technology has made considerable progress with the application of the parity-time (PT) symmetry concept. In this Letter, we extend the standard second-order PT-symmetric Hamiltonian to a high-order symmetric tridiagonal pseudo-Hermitian Hamiltonian, relaxing the limitation of multisource/multiload systems based on non-Hermitian physics. We propose a three-mode pseudo-Hermitian dual-transmitter-single-receiver circuit and demonstrate that robust efficiency and stable frequency WPT can be attained despite the absence of PT symmetry. In addition, no active tuning is required when the coupling coefficient between the intermediate transmitter and the receiver is changed. The application of pseudo-Hermitian theory to classical circuit systems opens up an avenue for expanding the application of coupled multicoil systems.

Long-Term Consumption of Nuts (Including Peanuts, Peanut Butter, Walnuts, and Other Nuts) in Relation to Risk of Frailty in Older Women: Evidence from a Cohort Study.

BACKGROUND: Adherence to a healthy diet is inversely associated with frailty. However, the relationship between nuts, a key food group of Mediterranean diet, and frailty is unclear. OBJECTIVES: This study aimed to evaluate the association between nut consumption and frailty in an aging female population. METHODS: This population-based observational study included nonfrail women (≥60 y old) in the NHS from 11 states of the United States. Outcome was incident frailty, defined as having ≥3 of the FRAIL components (fatigue, lower strength, reduced aerobic capacity, multiple chronic conditions, and significant weight loss) and assessed every 4 y from 1992 to 2016. From 1990 to 2014, FFQs were used to assess the intakes of peanuts, peanut butter, walnuts (added in 1998), and other nuts at 4-y intervals. Exposure was total nut consumption, calculated as the sum of intakes of peanuts, peanut butter, walnuts, and other nuts and categorized into <1 serving/mo, 1-3 servings/mo, 1 serving/wk, 2-4 servings/wk, and ≥5 servings/wk. The relations of intakes of peanuts, peanut butter, and walnuts with frailty were also investigated separately. Cox proportional hazards models were used to assess the associations between nut consumption and frailty after adjusting for age, smoking, BMI, EI, diet quality, and medication use. RESULTS: Among 71,704 participants, 14,195 incident frailty cases occurred over 1,165,290 person-years. The adjusted HR (95% CI) for consuming ≥5 servings/wk of nuts was 0.80 (0.73, 0.87), as compared with <1 serving/mo. Higher intakes of peanuts and walnuts, but not peanut butter, were also inversely associated with frailty. CONCLUSIONS: This large prospective cohort study showed a strong and consistent inverse association between regular nut consumption and incident frailty. This suggests that nut consumption should be further tested as a convenient public health intervention for the preservation of health and well-being in older adults.

Effect of sandwiched YbCl3layer thickness on exciton dynamics of Yb3+doped CsPbCl3perovskite photodetectors.

Yb3+doped CsPbCl3metal halide perovskite photodetectors (PDs) in the structure of CsPbCl3(50 nm)/YbCl3(xnm)/CsPbCl3(50 nm), in whichxranges from 10 to 40 nm corresponding to the molar ratio from 6.3% to 25.2%, are fabricated by thermal evaporation on Si/SiO2substrate. Photoresponse from 350 to 980 nm have been achieved with the optimal responsivity (R) of 3959, 5425, 955 A W-1for the case of 20 nm YbCl3at the wavelength (λ) of 420, 680 and 980 nm, respectively. A series of photophysical and electrical characterization has been performed and it is found that the remarkably improved photoresponse originates from the combining effects of upconversion and defects passivation from Yb3+. Moreover, the optimal YbCl3thickness of 20 nm can be ascribed to the balance between upconversion and concentration quenching of Yb3+. The influence of the YbCl3doping on the CsPbCl3electronic structure is investigated and downshifting and stabilization of valence band maximum (VBM) can be attributed to the p-type doping and counteracting effect of Yb3+and Cl-, respectively.

A GP130-Targeting Small Molecule, LMT-28, Reduces LPS-Induced Bone Resorption around Implants in Diabetic Models by Inhibiting IL-6/GP130/JAK2/STAT3 Signaling.

In this study, we examined the effect of the GP130-targeting molecule, LMT-28, on lipopolysaccharide- (LPS-) induced bone resorption around implants in diabetic models using in vitro and rat animal experiments. First, LMT-28 was added to osteoblasts stimulated by LPS and advanced glycation end products (AGEs), and nuclear factor-κB receptor-activating factor ligand (RANKL) and associated pathways were evaluated. Then, LMT-28 was administered by gavage at 0.23 mg/kg once every 5 days for 2 weeks to type 2 diabetic rats with peri-implantitis induced by LPS injection and silk ligature. The expression of IL-6 and RANKL was evaluated by immunohistochemistry, and the bone resorption around implants was evaluated by microcomputed tomography. The results showed that LMT-28 downregulated the expression of RANKL through the JAK2/STAT3 signaling pathway in osteoblasts stimulated by LPS and AGEs, reduced bone resorption around implants with peri-implantitis, decreased the expression of IL-6 and RANKL, and decreased osteoclast activity in type 2 diabetic rats. This study confirmed the ability of LMT-28 to reduce LPS-induced bone resorption around implants in diabetic rats.

Complexation of starch and phenolic compounds during food processing and impacts on the release of phenolic compounds.

Phenolic compounds can form complexes with starch during food processing, which can modulate the release of phenolic compounds in the gastrointestinal tract and regulate the bioaccessibility of phenolic compounds. The starch-phenolic complexation is determined by the structure of starch, phenolic compounds, and the food processing conditions. In this review, the complexation between starch and phenolic compounds during (hydro)thermal and nonthermal processing is reviewed. A hypothesis on the complexation kinetics is developed to elucidate the mechanism of complexation between starch and phenolic compounds considering the reaction time and the processing conditions. The subsequent effects of complexation on the physicochemical properties of starch, including gelatinization, retrogradation, and digestion, are critically articulated. Further, the release of phenolic substances and the bioaccessibility of different types of starch-phenolics complexes are discussed. The review emphasizes that the processing-induced structural changes of starch are the major determinant modulating the extent and manner of complexation with phenolic compounds. The controlled release of complexes formed between phenolic compounds and starch in the digestive tracts can modify the functionality of starch-based foods and, thus, can be used for both the modulation of glycemic response and the targeted delivery of phenolic compounds.

Exciton dynamics and photoresponse behavior of thein situannealed CsSnBr3perovskite films synthesized by thermal evaporation.

The CsSnBr3photodetectors are fabricated by thermal evaporation and 75 °Cin situannealing, and the effect ofin situannealing on the morphology, structure, exciton dynamics and photoresponse of thermally evaporated CsSnBr3films are investigated. Especially, temperature dependent steady-state photoluminescence (PL) and transient PL decaying have been analyzed in details for understanding the exciton dynamics. Meanwhile, effect of annealing on the activation energy for trap sites (Ea), exciton binding energy (Eb), activation energy for interfacial trapped carriers (ΔE), trap densities and carriers mobilities are studied and the annealed (A-CsSnBr3) reveals obviously lowerEband trap density together with notably higher carrier mobility than those of the unannealed (UA-CsSnBr3). Temperature dependence of the integrated PL intensity can be ascribed to the combining effect of the exciton dissociation, exciton quenching through trap sites and thermal activation of trapped carriers. The temperature dependent transient PL decaying analysis indicates that the PL decaying mechanism at low and high temperature is totally different from that in intermediate temperature range, in which combing effect of free exciton and localized state exciton decaying prevail. The beneficial effects of thein situannealing on the photoresponse performance of the CsSnBr3films can be demonstrated by the remarkable enhancement of the optimal responsivity (R) afterin situannealing which increases from less than 1 A W-1to 1350 A W-1as well as dramatically improved noise equivalent power, specific detectivityD* and Gain (G).

Evaluation of Factors Associated with Anxiety and Depression in Chinese Visiting Scholars in the United States During the COVID-19 Pandemic Assessed by Online Questionnaires.

BACKGROUND This study aimed to use online questionnaires to evaluate the factors associated with anxiety and depression in Chinese visiting scholars in the United States during the COVID-19 pandemic. MATERIAL AND METHODS Using a cross-sectional design, 311 Chinese scholars visiting 41 states in the United States were interviewed on 20 and 21 April 2020 through WeChat using the Patient Health Questionnaire-9 (PHQ-9) and the Generalized Anxiety Disorder-7 (GAD-7) questionnaire. RESULTS Of these 311 visiting scholars, 69 (22.2%) reported no symptoms of anxiety or depression, whereas 63 (20.3%) reported severe anxiety and 67 (21.5%) reported severe depression. Risk of anxiety was 93% higher in visiting scholars with than without accompanying parents in the US (odds ratio [OR], 1.93; 95% confidence interval [CI], 1.01-3.68) and was 1.72-fold (95% CI, 1.04-2.84) higher in those experiencing stress about family members with COVID-19. Stresses about personal security and return to China on schedule were associated with 1.73-fold (95% CI, 1.03-2.92) and 3.00-fold (95% CI, 1.51-5.95) higher risks of anxiety, respectively. Risks of depression were 1.86-fold (95% CI, 1.14-3.05), 1.84-fold (95% CI, 1.10-3.07), and 3.45-fold (95% CI, 1.72-6.92) higher in visiting Chinese scholars who were than were not experiencing stresses about financial support, personal security and return to China on schedule, respectively. CONCLUSIONS Chinese scholars visiting the United States during the COVID-19 pandemic experienced severe psychological distress. Surveys that include larger numbers of visiting scholars are warranted.

Genome-wide identification and expression profiling of glutathione transferase gene family under multiple stresses and hormone treatments in wheat (Triticum aestivum L.).

BACKGROUND: Glutathione transferases (GSTs), the ancient, ubiquitous and multi-functional proteins, play significant roles in development, metabolism as well as abiotic and biotic stress responses in plants. Wheat is one of the most important crops, but the functions of GST genes in wheat were less studied. RESULTS: A total of 330 TaGST genes were identified from the wheat genome and named according to the nomenclature of rice and Arabidopsis GST genes. They were classified into eight classes based on the phylogenetic relationship among wheat, rice, and Arabidopsis, and their gene structure and conserved motif were similar in the same phylogenetic class. The 43 and 171 gene pairs were identified as tandem and segmental duplication genes respectively, and the Ka/Ks ratios of tandem and segmental duplication TaGST genes were less than 1 except segmental duplication gene pair TaGSTU24/TaGSTU154. The 59 TaGST genes were identified to have syntenic relationships with 28 OsGST genes. The expression profiling involved in 15 tissues and biotic and abiotic stresses suggested the different expression and response patterns of the TaGST genes. Furthermore, the qRT-PCR data showed that GST could response to abiotic stresses and hormones extensively in wheat. CONCLUSIONS: In this study, a large GST family with 330 members was identified from the wheat genome. Duplication events containing tandem and segmental duplication contributed to the expansion of TaGST family, and duplication genes might undergo extensive purifying selection. The expression profiling and cis-elements in promoter region of 330 TaGST genes implied their roles in growth and development as well as adaption to stressful environments. The qRT-PCR data of 14 TaGST genes revealed that they could respond to different abiotic stresses and hormones, especially salt stress and abscisic acid. In conclusion, this study contributed to the further functional analysis of GST genes family in wheat.

Evaluation of the Direct MacConkey Method for Identification of Carbapenem-Resistant Gram-Negative Organisms from Rectal Swabs: Reevaluating Zone Diameter Cutoffs.

The optimal method to screen for gastrointestinal colonization with carbapenem-resistant organisms (CRO) has yet to be established. The direct MacConkey (direct MAC) plate method demonstrates high sensitivity for CRO detection, but established zone diameter (ZD) criteria for ertapenem (≤27 mm) and meropenem (≤32 mm) result in high rates of false positives upon confirmatory testing. To increase specificity, we screened for CRO in two high-risk wards using the direct MAC plate method, recorded ZDs for each sample, and generated receiver operating characteristic (ROC) curves to evaluate the optimal ZD cutoff criteria. Of 6,868 swabs obtained over an 18-month period, 4,766 (69%) had growth on MAC plates, and 2,500 (36%) met criteria for further evaluation based on previously established ZDs around the carbapenem disks. A total of 812 (12%) swabs were confirmed positive for at least one CRO and included 213 (3%) carbapenemase-producing organisms (CPO), resulting in a specificity of 78% for the direct MAC plate method. Reducing the ertapenem and meropenem ZDs to ≤25 mm improved specificity to 83%, decreasing the confirmatory testing workload by 32%. The sensitivities with the lower ZD criteria were 89% for CRO and 94% for CPO, respectively. The direct MAC plate method criteria for CRO testing can be modified to balance the sensitivity and specificity of CRO while reducing the burden on clinical microbiology laboratories. These modifications can be particularly helpful in regions with a low CRO prevalence.

Kidney disease risk factors associate with urine biomarkers concentrations in HIV-positive persons; a cross-sectional study.

BACKGROUND: HIV-positive persons bear an excess burden of chronic kidney disease (CKD); however, conventional methods to assess kidney health are insensitive and non-specific for detecting early kidney injury. Urinary biomarkers can detect early kidney injury, and may help mitigate the risk of overt CKD. METHODS: Cross-sectional study of HIV-positive persons in the Multicenter AIDS Cohort Study and the Women's Interagency HIV Study. We measured levels of 14 biomarkers, capturing multiple dimensions of kidney injury. We then evaluated associations of known CKD risk factors with urine biomarkers using separate multivariable adjusted models for each biomarker. RESULTS: Of the 198 participants, one third were on HAART and virally suppressed. The vast majority (95%) had preserved kidney function as assessed by serum creatinine, with a median eGFR of 103 ml/min/1.73 m2 (interquartile range (IQR): 88, 116). In our multivariable analyses, the associations of each CKD risk factor with urinary biomarker levels varied in magnitude. For example, HIV viral load was predominantly associated with elevations in interleukin(IL)-18, and albuminuria, while higher CD4 levels were associated with lower monocyte chemoattractant protein-1 (MCP-1) and ß2-microglobulin. In contrast, older age was significantly associated with elevations in α1-microglobulin, kidney injury marker-1, clusterin, MCP-1, and chitinase-3-like protein-1 levels, as well as lower epidermal growth factor, and uromodulin levels. CONCLUSIONS: Among HIV-positive persons, CKD risk factors are associated with unique and heterogeneous patterns of changes in urine biomarkers levels. Additional work is needed to develop parsimonious algorithms that integrate multiple biomarkers and clinical data to discern the risk of overt CKD and its progression.

Relationship Between T-Cell Responses to CMV, Markers of Inflammation, and Frailty in HIV-uninfected and HIV-infected Men in the Multicenter AIDS Cohort Study.

Background: Both aging and treated human immunodeficiency virus (HIV)-infected populations exhibit low-level chronic immune activation of unknown etiology, which correlates with morbidity and mortality. Cytomegalovirus (CMV) infection is common in both populations, but its relation to immune activation is unknown. Methods: T cells from men who have sex with men (22 virologically suppressed HIV+, 20 HIV-) were stimulated with peptides spanning 19 CMV open reading frames, and intracellular cytokine responses were assessed. Soluble and cellular inflammatory markers were assessed by multiplex electrochemiluminescence and flow cytometry, respectively. Frailty was assessed by the Fried criteria. Results: All men had responses to CMV. Proportions of CMV-responsive T cells correlated strongly (r ≥ 0.6 or ≤ -0.6; P < .05) with immunologic markers, depending on donor HIV and frailty status. Markers significantly correlated in some groups after adjustment for multiple comparisons included interferon-γ, tumor necrosis factor-α, interleukin-6, and several chemokines in serum, and the proportion of activated T cells. The magnitude of the CD4 IL-2 response significantly predicted onset of frailty in HIV- nonfrail men, but not in HIV+ nonfrail men. Conclusions: T-cell responses to CMV may strongly influence chronic immune activation in HIV-uninfected and virologically suppressed HIV-infected men, and may predict frailty in HIV-uninfected men.

Chiral Organic Cages with a Triple-Stranded Helical Structure Derived from Helicene.

We report the use of helicene with an intrinsic helical molecular structure to prepare covalent organic cages via imine condensation. The organic cages revealed a [3+2]-type architecture containing a triple-stranded helical structure with three helicene units arranged in a propeller-like fashion with the framework integrally twisted. Such structural chirality was retained upon dissolution in organic solvents, as indicated by a strong diastereotopy effect in proton NMR and unique Cotton effects in circular dichroism spectra. Further study on chiral adsorption showed that the chiral organic cages possess considerable enantioselectivity toward a series of aromatic racemates.

Ectopic expression of BdCIPK31 confers enhanced low-temperature tolerance in transgenic tobacco plants.

Calcineurin B-like protein (CBL), the Ca2+ sensor, and its interacting protein kinases (CIPKs) play essential roles in plants' response to stress. However, few studies have focused on the functions of CIPKs in low-temperature response. In the present study, BdCIPK31, a cold-responsive CIPK in Brachypodium distachyon, was found to participate in low-temperature response. Ectopic expression of BdCIPK31 conferred cold tolerance in transgenic tobaccos. Further analyses indicated that expression of BdCIPK31 improved ROS detoxication and omsoprotectant biosynthesis in transgenic plants under low-temperature treatment, suggesting that the BdCIPK31 functions positively in plant adaption to the cold-induced oxidative and osmotic stresses. Moreover, BdCIPK31 could upregulate the expressions of some representative stress-related genes under cold stress. In conclusion, these findings suggest that BdCIPK31 functions positively in plant cold response.

A Molecular Recognition Approach To Synthesize Nucleoside Analogue Based Multifunctional Nanoparticles for Targeted Cancer Therapy.

Tumor-targeted drug delivery with simultaneous cancer imaging is highly desirable for personalized medicine. Herein, we report a supramolecular approach to design a promising class of multifunctional nanoparticles based on molecular recognition of nucleobases, which combine excellent tumor-targeting capability via aptamer, controlled drug release, and efficient fluorescent imaging for cancer-specific therapy. First, an amphiphilic prodrug dioleoyl clofarabine was self-assembled into micellar nanoparticles with hydrophilic nucleoside analogue clofarabine on their surface. Thereafter, two types of single-stranded DNAs that contain the aptamer motif and fluorescent probe Cy5.5, respectively, were introduced onto the surface of the nanoparticles via molecular recognition between the clofarabine and the thymine on DNA. These drug-containing multifunctional nanoparticles exhibit good capabilities of targeted clofarabine delivery to the tumor site and intracellular controlled drug release, leading to a robust and effective antitumor effect in vivo.

Sustained impact of a rapid microarray-based assay with antimicrobial stewardship interventions on optimizing therapy in patients with Gram-positive bacteraemia.

OBJECTIVES: To compare antibiotic optimization and outcomes of patients before implementation of the Verigene Gram-Positive Blood Culture (Verigene BC-GP) nucleic acid microarray assay to after implementation with antimicrobial stewardship (AS) interventions and after discontinuation of AS interventions. METHODS: A retrospective pre-post-post quasi-experimental study was conducted to compare the three periods. AS interventions consisted of real-time guidance to clinicians on antibiotic selection. The primary outcome was median time from Gram stain to optimal therapy. Secondary outcomes included median time to effective therapy, median duration of therapy for contaminant organisms, median length of stay after blood cultures were collected, and all-cause in-hospital mortality. RESULTS: Out of a total of 923 patients, 390 (125 baseline, 134 intervention, 131 post-intervention) who were not on optimal therapy at the time of Gram stain or had contaminated blood cultures were assessed. Compared with baseline, only the median time to optimal therapy for MSSA bacteraemia was reduced in both the intervention and post-intervention periods (17 versus 17 versus 50 h; P < 0.001), respectively. In an analysis adjusted for baseline differences among the groups using quantile regression models, use of the Verigene BC-GP assay in both periods significantly reduced time to optimal therapy by 14-22 h in patients who would achieve optimal therapy at ≥ 26 h without the assay. There were no differences in in-hospital mortality or hospital length of stay between study periods. CONCLUSIONS: A real-time AS intervention implemented alongside introduction of the Verigene BC-GP assay led to improvements in antibiotic therapy for patients with bacteraemia due to Gram-positive cocci, even after the AS intervention was discontinued.

Assessing the Eventual Publication of Clinical Trial Abstracts Submitted to a Large Annual Oncology Meeting.

BACKGROUND: Despite the ethical imperative to publish clinical trials when human subjects are involved, such data frequently remain unpublished. The objectives were to tabulate the rate and ascertain factors associated with eventual publication of clinical trial results reported as abstracts in the Proceedings of the American Society of Clinical Oncology (American Society of Clinical Oncology). MATERIALS AND METHODS: Abstracts describing clinical trials for patients with breast, lung, colorectal, ovarian, and prostate cancer from 2009 to 2011 were identified by using a comprehensive online database (http://meetinglibrary.asco.org/abstracts). Abstracts included reported results of a treatment or intervention assessed in a discrete, prospective clinical trial. Publication status at 4-6 years was determined by using a standardized search of PubMed. Primary outcomes were the rate of publication for abstracts of randomized and nonrandomized clinical trials. Secondary outcomes included factors influencing the publication of results. RESULTS: A total of 1,075 abstracts describing 378 randomized and 697 nonrandomized clinical trials were evaluated. Across all years, 75% of randomized and 54% of nonrandomized trials were published, with an overall publication rate of 61%. Sample size was a statistically significant predictor of publication for both randomized and nonrandomized trials (odds ratio [OR] per increase of 100 participants = 1.23 [1.11-1.36], p < .001; and 1.64 [1.15-2.34], p = .006, respectively). Among randomized studies, an industry coauthor or involvement of a cooperative group increased the likelihood of publication (OR 2.37, p = .013; and 2.21, p = .01, respectively). Among nonrandomized studies, phase II trials were more likely to be published than phase I (p < .001). Use of an experimental agent was not a predictor of publication in randomized (OR 0.76 [0.38-1.52]; p = .441) or nonrandomized trials (OR 0.89 [0.61-1.29]; p = .532). CONCLUSION: This is the largest reported study examining why oncology trials are not published. The data show that 4-6 years after appearing as abstracts, 39% of oncology clinical trials remain unpublished. Larger sample size and advanced trial phase were associated with eventual publication; among randomized trials, an industry-affiliated author or a cooperative group increased likelihood of publication. Unfortunately, we found that, despite widespread recognition of the problem and the creation of central data repositories, timely publishing of oncology clinical trials results remains unsatisfactory.

Cytokine-induced killer cell infusion combined with conventional treatments produced better prognosis for hepatocellular carcinoma patients with barcelona clinic liver cancer B or earlier stage: A systematic review and meta-analysis.

BACKGROUND AIMS: To investigate the clinical benefits of cytokine-induced killer (CIK) cell infusions on hepatocellular carcinoma (HCC) patients, combined with other conventional treatments. METHODS: This was a systematic review and meta-analysis conducted among phase II and III randomized control trials worldwide. Review manager 5.2 version was used to pool the effect size across studies. Sensitivity analyses and risk of bias were estimated among included studies. Egger's test was used to characterize the publication bias. RESULTS: Eight randomized controlled trials and 945 patients with HCC were included in the study. CIK infusion reduced cancer recurrence risk to 0.74 (95% confidence interval [CI] 0.5-0.92), I2 75% (P <0.001), and reduced cancer death risk to 0.76 (95% CI 0.65-0.88), I2 50% (P = 0.09). Among studies blinded for outcome assessment and Barcelona Clinic Liver Cancer stages of 0, A and B, CIK infusion reduced recurrence risk by 18% (relative risk [RR] = 0.82, 95% CI 0.70-0.96) and death risk by 37% (RR = 0.63, 95% CI 0.47-0.85); heterogeneity was 0% and 39%, respectively (P > 0.05). The intercepts of linear regressions for recurrence and death were -2.17 and -2.07, respectively, but the P value was 0.17 and 0.38; no significant publication bias was observed with Egger's test. DISCUSSION: Among hepatocellular carcinoma patients with Barcelona Clinic Liver Cancer score of B or less, CIK cell infusions combined with conventional treatments significantly prolonged recurrence-free and overall survival. This adoptive immunotherapy could be recommended to HCC patients.

Aptamer-Functionalized and Backbone Redox-Responsive Hyperbranched Polymer for Targeted Drug Delivery in Cancer Therapy.

A novel type of backbone redox-responsive hyperbranched poly(2-((2-(acryloyloxy)ethyl)disulfanyl)ethyl 4-cyano-4-(((propylthio)carbonothioyl)-thio)-pentanoate-co-poly(ethylene glycol) methacrylate) (HPAEG) has been designed and prepared successfully via the combination of reversible addition-fragmentation chain-transfer (RAFT) polymerization and self-condensing vinyl polymerization (SCVP). Owing to the existence of surface vinyl groups, HPAEG could be efficiently functionalized by DNA aptamer AS1411 via Michael addition reaction to obtain an active tumor targeting drug delivery carrier (HPAEG-AS1411). The amphiphilic HPAEG-AS1411 could form nanoparticles by macromolecular self-assembly strategy. Cell Counting Kit-8 (CCK-8) assay illustrated that HPAEG-AS1411 nanoparticles had low cytotoxicity to normal cell line. Flow cytometry and confocal laser scanning microscopy (CLSM) results demonstrated that HPAEG-AS1411 nanoparticles could be internalized into tumor cells via aptamer-mediated endocytosis. Compared with pure HPAEG nanoparticles, HPAEG-AS1411 nanoparticles displayed enhanced tumor cell uptake. When the HPAEG-AS1411 nanoparticles loaded with anticancer drug doxorubicin (DOX) were internalized into tumor cells, the disulfide bonds in the backbone of HPAEG-AS1411 were cleaved by glutathione (GSH) in the cytoplasm, so that DOX was released rapidly. Therefore, DOX-loaded HPAEG-AS1411 nanoparticles exhibited a high tumor cellular proliferation inhibition rate and low cytotoxicity to normal cells. This aptamer-functionalized and backbone redox-responsive hyperbranched polymer provides a promising platform for targeted drug delivery in cancer therapy.