Operando Spectroscopic Elucidation of the Bubble Sunshade Effect in Inorganic-Biological Hybrids for Photosynthetic Hydrogen Production.

Hydrogen production by photosynthetic hybrid systems (PBSs) offers a promising avenue for renewable energy. However, the light-harvesting efficiency of PBSs remains constrained due to unclear intracellular kinetic factors. Here, we present an operando elucidation of the sluggish light-harvesting behavior for existing PBSs and strategies to circumvent them. By quantifying the spectral shift in the structural color scattering of individual PBSs during the photosynthetic process, we observe the accumulation of product hydrogen bubbles on their outer membrane. These bubbles act as a sunshade and inhibit light absorption. This phenomenon elucidates the intrinsic constraints on the light-harvesting efficiency of PBSs. The introduction of a tension eliminator into the PBSs effectively improves the bubble sunshade effect and results in a 4.5-fold increase in the light-harvesting efficiency. This work provides valuable insights into the dynamics of transmembrane transport gas products and holds the potential to inspire innovative designs for improving the light-harvesting efficiency of PBSs.

Activation of the PPARγ/NF-κB pathway by A-MPDA@Fe3O4@PVP via scavenging reactive oxygen species to alleviate hepatic ischemia-reperfusion injury.

Hepatic ischemia-reperfusion injury (IRI) is a common pathological process during hepatectomy and liver transplantation and the two primary reasons for hepatic IRI are reactive oxygen species (ROS)-mediated oxidative stress and excessive inflammatory responses. Herein, a novel antioxidant nanodrug (A-MPDA@Fe3O4@PVP) is prepared by employing L-arginine-doped mesoporous polydopamine (A-MPDA) nanoparticles as the carrier for deposition of ultra-small ferric oxide (Fe3O4) nanoparticles and further surface modification with polyvinylpyrrolidone (PVP). A-MPDA@Fe3O4@PVP not only effectively reduces the aggregation of ultra-small Fe3O4, but also simultaneously replicates the catalytic activity of catalase (CAT) and superoxide dismutase (SOD). A-MPDA@Fe3O4@PVP with good antioxidant activity can rapidly remove various toxic reactive oxygen species (ROS) and effectively regulate macrophage polarization in vitro. In the treatment of hepatic IRI, A-MPDA@Fe3O4@PVP effectively alleviates ROS-induced oxidative stress, reduces the expression of inflammatory factors, and prevents apoptosis of hepatocytes through immune regulation. A-MPDA@Fe3O4@PVP can further protect liver tissue by activating the PPARγ/NF-κB pathway. This multiplex antioxidant enzyme therapy can provide new references for the treatment of IRI in organ transplantation and other ROS-related injuries such as fibrosis, cirrhosis, and bacterial and hepatic viral infection.

Factors Influencing Early Diagnosis and Poor Prognosis of Dysphagia After Senile Ischemic Stroke.

Dysphagia is often a long-term problem after ischemic stroke, which are often accompanied by complications and results in poor outcome. This study aimed to investigate the influencing factors associated with the prognosis of dysphagia after senile ischemic stroke and evaluate the diagnostic performance of crucial factors. A total of 192 elderly ischemic stroke patients (96 patients without dysphagia with average age of 69.81 ± 4.61 years and 96 patients with dysphagia with average of 70.00 ± 6.66 years) were enrolled in the retrospective study. The clinical factors of the patients were collected and recorded for chi-square analysis and logistic analysis. The receiver operating characteristic (ROC) curve was performed to evaluate the diagnostic performance of international normalized ratio (INR) and homocysteine (Hcy) in senile ischemic stroke patients. The age, cough reflex, history of stroke, mechanical ventilation, eating posture, insufficient elevation of the larynx, standard swallowing assessment (SSA) score, Hcy value, and INR were closely related to endpoint events of patients with dysphagia. The joint model (combined INR and Hcy value) can increase the area under the curve (AUC) value (0.948) with higher sensitivity and specificity for predicting patients with dysphagia occurred endpoint events. The influencing factors for older ischemic stroke patients with dysphagia include age, cough reflex, history of stroke, mechanical ventilation, eating posture, insufficient elevation of the larynx, SSA score, Hcy value, and INR. INR and Hcy were independent risk factors for prognosis and diagnostic markers for patients with dysphagia after senile ischemic stroke.

Overexpression of NtLHT1 affects the development of leaf morphology and abiotic tolerance in tobacco.

LYSINE HISTIDINE TRANSPORTER1 (LHT1) is a crucial broad-specificity and high-affinity amino acid transporter affecting the uptake of nitrogen and probably the tolerance to abiotic stress in plants. However, little is known about the phenotypic functions of LHT1 in plant growth and development and abiotic stress tolerance. In this study, we identified the NtLHT1 gene from the tobacco variety Honghuadajinyuan (HD) and determined its important roles in leaf morphological development and plant resistance to abiotic stress. Comprehensive functional analyses using knockout and overexpression transgenic lines (ntlht1 and OE) revealed overexpression of NtLHT1 accelerated leave senescence and increased plant height, leaf number and plant tolerance under cold, salt and drought stresses. In addition, NtLHT1 overexpression significantly decreased the leaf elongation of HD, causing the leaves to change from a long-elliptical shape to an elliptical shape. However silencing NtLHT1 decreased the seed germination rate under NaCl and PEG stresses. Moreover, NtLHT1 significantly affected the contents of various amino acids, such as the neutral, acidic, non-polar and aromatic amino acids, ethylene precursor (ACC), GA3 and IAA in tobacco. These results suggested that the amino acid and ethylene precursor ACC transport activities of NtLHT1 provide fine regulatory function for plant growth and development and plant tolerance to abiotic stress.

Enrollment Success, Factors, and Prediction Models in Cancer Trials (2008-2019).

PURPOSE: To investigate the enrollment success rate of cancer clinical trials conducted in 2008-2019 and various factors lowering the enrollment success rate. METHODS: This is a cross-sectional study with clinical trial information from the largest registration database ClinicalTrials.gov. Enrollment success rate was defined as actual enrollment greater or equal to 85% of the estimated enrollment goal. The association between trial characteristics and enrollment success was evaluated using the multivariable logistic regression. RESULTS: A total of 4,004 trials in breast, lung, and colorectal cancers were included. The overall enrollment success rate was 49.1%. Compared with 2008-2010 (51.5%) and 2011-2013 (52.1%), the enrollment success rate is lower in 2014-2016 (46.5%) and 2017-2019 (36.4%). Regression analyses found trial activation year, phase I, phase I/phase II, and phase II (v phase III), sponsor agency of government (v industry), not requiring healthy volunteers, and estimated enrollment of 50-100, 100-200, 200, and >500 (v 0-50) were associated with a lower enrollment success rate (P < .05). However, trials with placebo comparator, ≥5 locations (v 1 location), and a higher number of secondary end points (eg, ≥5 v 0) were associated with a higher enrollment success rate (P < .05). The AUC for prediction of the final logistic regression models for all trials and specific trial groups ranged from 0.69 to 0.76. CONCLUSION: This large-scale study supports a lower enrollment success rate over years in cancer clinical trials. Identified factors for enrollment success can be used to develop and improve recruitment strategies for future cancer trials.

The colonic metabolism differences of main alkaloids in normal and colitis mice treated with Coptis chinensis Franch. and Sophora flavescens Ait. herbal pair using liquid chromatography-high resolution mass spectrometry method combined with chemometrics.

Coptis chinensis Franch. and Sophora flavescens Ait. is a herbal pair frequently used in treating ulcerative colitis. However, the bio-disposition profile of the major components in the inflamed gut remains unclear, which is essential to understand the pharmacological material basis of this herb pair. Here we established an integral quantitative and chemometric method to deduce the colonic metabolism differences of this herbal pair in normal and colitis mice. With this LC-MS method, a total of 41 components have been found in the Coptis chinensis Franch. and Sophora flavescens Ait. extract, and 28 metabolites were found in the colon after oral administration. Alkaloid and its phase I metabolites were the main components in the colon of normal and colitis mice. The results of principal component analysis at 6 h after oral administration showed significant colonic metabolism differences between normal and colitis mice. Heamap results showed that colitis induced significant changes in the colonic bio-disposition of this herbal pair extract. In particular, in the context of colitis, the phase I metabolism of berberine, coptisine, jatrorrhizine, palmatine,and epiberberine has been inhibited. These results may provide a basis for understanding the pharmacological material basis of Coptis chinensis Franch. and Sophora flavescens Ait. in treating ulcerative colitis.

Reversible Regulation of Long-Distance Charge Transport in DNA Nanowires by Dynamically Controlling Steric Conformation.

Understanding of DNA-mediated charge transport (CT) is significant for exploring circuits at the molecular scale. However, the fabrication of robust DNA wires remains challenging due to the persistence length and natural flexibility of DNA molecules. Moreover, CT regulation in DNA wires often relies on predesigned sequences, which limit their application and scalability. Here, we addressed these issues by preparing self-assembled DNA nanowires with lengths of 30-120 nm using structural DNA nanotechnology. We employed these nanowires to plug individual gold nanoparticles into a circuit and measured the transport current in nanowires with an optical imaging technique. Contrary to the reported cases with shallow or no length dependence, a fair current attenuation was observed with increasing nanowire length, which experimentally confirmed the prediction of the incoherent hopping model. We also reported a mechanism for the reversible CT regulation in DNA nanowires, which involves dynamic transitions in the steric conformation.

Global trends in the burden of esophageal cancer, 1990-2019: results from the Global Burden of Disease Study 2019.

Background: Esophageal cancer is one of the leading causes of cancer death worldwide. A deeper understanding of the trends in annual incidence, mortality, and disability-adjusted life-years (DALYs) of esophageal cancer is critical for management and prevention. In this study, we report on the disease burden of esophageal cancer in 204 countries and territories between 1990 and 2019 by age, sex, and sociodemographic index (SDI). Methods: Data on incidence, mortality, and DALYs were extracted from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. The estimated numbers and age-standardized rates for esophageal cancer in 2019 are presented in this paper, as well as trends from 1990 to 2019. All estimates are presented as counts and age-standardized rates per 100,000 population, with 95% uncertainty intervals (UIs) for each estimate. Results: In 2019, nearly 535,000 (95% UI: 467,000-595,000) new cases of esophageal cancer occurred globally. Esophageal cancer was responsible for more than 498,000 (95% UI: 438,000-551,000) deaths and 11.7 million (95% UI: 10.4-12.9 million) DALYs. Worldwide age-standardized rates of esophageal cancer, including incidence, deaths, and DALYs, have declined since 1990. However, the trends differ across countries and territories. Notably, there was a nonlinear but generally inverse correlation between age-standardized DALY rates and SDI. Higher age-standardized incidence and death rates were observed in males compared to females, and both increased with age. Regarding risk factors, smoking, alcohol use, and high body-mass index were 3 predominant contributors to esophageal cancer DALYs in 2019 for both sexes worldwide. Conclusions: This study found a global reduction in the esophageal cancer burden, but substantial heterogeneity remains across regions and countries. Hence, the identification of high-risk groups and the exploration of specific local strategies and primary prevention efforts are required.

Advances in self-assembled Au-DNA nanomachines.

Au-DNA self-assembled nanomachines can perform intelligent tasks such as sensing biomarkers and delivery of drug molecules through rational customization and programming. By virtue of their efficient signal amplification and flexible scalability, Au-DNA nanomachines have developed into one of the most promising nanodevices. In this review, we summarize the latest progress in Au-DNA self-assembled nanomachines for biosensing applications. First, the functional modules for building Au-DNA nanomachines are introduced. Subsequently, we summarize the biosensing applications of Au-DNA nanomachines with electrochemical or fluorescent signals as the output, respectively. Finally, we discuss the challenges and potential opportunities for Au-DNA nanomachines in biomedical applications.

Miniaturized Microfluidic Electrochemical Biosensors Powered by Enzymatic Biofuel Cell.

Electrochemical biosensors, in which enzymatic biofuel cells simultaneously work as energy power and signal generators, have become a research hotspot. They display the merits of power self-support, a simplified structure, in vivo operational feasibility, online and timely monitoring, etc. Since the concept of enzymatic biofuel cell-powered biosensors (EBFC-SPBs) was first proposed, its applications in health monitoring have scored tremendous achievements. However, the creation and practical application of portable EBFC-SPBs are still impeded by the difficulty in their miniaturization. In recent years, the booming microfluidic technology has powerfully pushed forward the progress made in miniaturized and portable EBFC-SPBs. This brief review recalls and summarizes the achievements and progress made in miniaturized EBFC-SPBs. In addition, we also discuss the advantages and challenges that microfluidic and screen-printing technologies provide to wearable and disposable EBFC-SPBs.

Antibacterial Carbon Dots-Based Composites.

The emergence and global spread of bacterial resistance to conventionally used antibiotics have highlighted the urgent need for new antimicrobial agents that might replace antibiotics. Currently, nanomaterials hold considerable promise as antimicrobial agents in anti-inflammatory therapy. Due to their distinctive functional physicochemical characteristics and exceptional biocompatibility, carbon dots (CDs)-based composites have attracted a lot of attention in the context of these antimicrobial nanomaterials. Here, a thorough assessment of current developments in the field of antimicrobial CDs-based composites is provided, starting with a brief explanation of the general synthesis procedures, categorization, and physicochemical characteristics of CDs-based composites. The many processes driving the antibacterial action of these composites are then thoroughly described, including physical destruction, oxidative stress, and the incorporation of antimicrobial agents. Finally, the obstacles that CDs-based composites now suffer in combating infectious diseases are outlined and investigated, along with the potential applications of antimicrobial CDs-based composites.

Surface passivation of intensely luminescent all-inorganic nanocrystals and their direct optical patterning.

All-inorganic nanocrystals (NCs) are of great importance in a range of electronic devices. However, current all-inorganic NCs suffer from limitations in their optical properties, such as low fluorescence efficiencies. Here, we develop a general surface treatment strategy to obtain intensely luminescent all-inorganic NCs (ILANs) by using designed metal salts with noncoordinating anions that play a dual role in the surface treatment process: (i) removing the original organic ligands and (ii) binding to unpassivated Lewis basic sites to preserve the photoluminescent (PL) properties of the NCs. The absolute photoluminescence quantum yields (PLQYs) of red-emitting CdSe/ZnS NCs, green-emitting CdSe/CdZnSeS/ZnS NCs and blue-emitting CdZnS/ZnS NCs in polar solvents are 97%, 80% and 72%, respectively. Further study reveals that the passivated Lewis basic sites of ILANs by metal cations boost the efficiency of radiative recombination of electron-hole pairs. While the passivation of Lewis basic sites leads to a high PLQY of ILANs, the exposed Lewis acidic sites provide the possibility for in situ tuning of the functions of NCs, creating opportunities for direct optical patterning of functional NCs with high resolution.

Effectiveness and implementation of models of cancer survivorship care: an overview of systematic reviews.

PURPOSE: To critically assess the effectiveness and implementation of different models of post-treatment cancer survivorship care compared to specialist-led models of survivorship care assessed in published systematic reviews. METHODS: MEDLINE, CINAHL, Embase, and Cochrane CENTRAL databases were searched from January 2005 to May 2021. Systematic reviews that compared at least two models of cancer survivorship care were included. Article selection, data extraction, and critical appraisal were conducted independently by two authors. The models were evaluated according to cancer survivorship care domains, patient and caregiver experience, communication and decision-making, care coordination, quality of life, healthcare utilization, costs, and mortality. Barriers and facilitators to implementation were also synthesized. RESULTS: Twelve systematic reviews were included, capturing 53 primary studies. Effectiveness for managing survivors' physical and psychosocial outcomes was found to be no different across models. Nurse-led and primary care provider-led models may produce cost savings to cancer survivors and healthcare systems. Barriers to the implementation of different models of care included limited resources, communication, and care coordination, while facilitators included survivor engagement, planning, and flexible services. CONCLUSIONS: Despite evidence regarding the equivalent effectiveness of nurse-led, primary care-led, or shared care models, these models are not widely adopted, and evidence-based recommendations to guide implementation are required. Further research is needed to address effectiveness in understudied domains of care and outcomes and across different population groups. IMPLICATIONS FOR CANCER SURVIVORS: Rather than aiming for an optimal "one-size fits all" model of survivorship care, applying the most appropriate model in distinct contexts can improve outcomes and healthcare efficiency.

A Telomerase-Assisted Strategy for Regeneration of DNA Nanomachines in Living Cells.

DNA nanomachines have been engineered into diverse personalized devices for diagnostic imaging of biomarkers; however, the regeneration of DNA nanomachines in living cells remains challenging. Here, we report an ingenious DNA nanomachine that can implement telomerase (TE)-activated regeneration in living cells. Upon apurinic/apyrimidinic endonuclease 1 (APE1)-responsive initiation of the nanomachine, the walker of the nanomachine moves along tracks regenerated by TE, generating multiply amplified signals through which APE1 can be imaged in situ. Additionally, augmentation of the signal due to the regeneration of the nanomachines could reveal differential expression of TE in different cell lines. To the best of our knowledge, this is the first proof-of-concept demonstration of the use of biomarkers to assist in the regeneration of nanomachines in living cells. This study offers a new paradigm for the development of more applicable and efficient DNA nanomachines.

General Synergistic Hybrid Catalyst Synthesis Method Using a Natural Enzyme Scaffold-Confined Metal Nanocluster.

Due to differences in the chemical properties or optimal reaction conditions of the catalysts, the challenge in the design of bio-chemical hybrid catalysts is that the bio-catalysts or chemical catalysts usually cannot maintain the initial catalytic performance. Herein, we report a general bio-chemical hybrid catalyst synthesis method using a natural enzyme scaffold-confined metal nanocluster. A redox-active enzyme is a nanoreactor that allows access to and reduces metal ions into metal nanoclusters in situ, resulting in the enzyme-confined metal nanocluster hybrid catalyst with a synergistic effect to boost catalytic performance. Specifically, bilirubin oxidase-Ir nanoclusters (BOD-Ir NCs) with catalytic properties for the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) are designed. The BOD-Ir NCs exhibit an approximately 2-fold ORR activity compared with pure BOD and a 4-fold OER activity compared with pure Ir NCs. BOD-Ir NCs exhibit stability for over 50,000 s, exceeding that of pure Ir NCs (22,000 s). The synergistic catalytic performance is attributed to the following: the mild preparation condition and matched sizes of BOD and the Ir NCs maintain the natural activity of BOD; the highly conductive Ir NCs improve the ORR activity of BOD; and the confining effect of BOD, which improves the stability and activity of the Ir NCs during the OER. In particular, BOD-Ir NCs exhibit a high half-wave potential of 0.97 V for the ORR and a low overpotential of 319 mV at 10 mA cm-2 for the OER, surpassing most of reported catalysts under neutral conditions. Furthermore, laccase-Ir NCs and glucose oxidase-Pd NCs with synergistic catalytic performances are fabricated, proving the universality of this synthetic method. This facile strategy for designing synergistic hybrid catalysts is expected to be applied to more complex chemical transformations.

Beta-glucan enhanced immune response to Newcastle disease vaccine and changed mRNA expression of spleen in chickens.

The present study was performed to investigate the effect of oral administration of ß-glucan (G70), a product obtained from the cell wall of yeast, on Newcastle disease virus (NDV)-specific hemagglutination inhibition (HI) titers, lymphocyte proliferation, and the role of T lymphocyte subpopulations in chickens treated with live NDV vaccine. In addition, the influence of ß-glucan on splenic gene expression was investigated by transcriptome sequencing. The results revealed that the supplementation of ß-glucan boosted the titer of serum NDV HI increased the NDV stimulation index of lymphocytes in peripheral blood and intestinal tract, and promoted the differentiation of T lymphocytes into CD4+ T cells. The RNA sequencing (RNA-seq) analysis demonstrated that G70 upregulated the mRNA expressions related to G-protein coupled receptor and MHC class I polypeptide, and downregulated the mRNA expressions related to cathelicidin and beta-defensin. The immunomodulatory effect of G70 might function through mitogen-activated protein kinase signaling pathway. To sum up, G70 could boost the immunological efficacy of live NDV vaccine in chickens and could be applied as a potential adjuvant candidate in the poultry industry.

Plasmonic Probing Single-Cell Bio-Current Waves with a Shrinking Magnetite Nanoprobe.

Probing of the single-cell level extracellular electron transfer highlights the maximum output current for microbial fuel cells (MFCs) at hundreds of femtoampere per cell, which is difficult to achieve by existing devices. Past studies focus on the external factors for boosting charge-extraction efficiency from bacteria. Here, we elucidate the intracellular factors that determine this output limit by monitoring the respiratory-driven shrinking kinetics of a single magnetite nanoprobe immobilized on a single Shewanella oneidensis MR-1 cell with plasmonic imaging. Quantified dissolving of nanoprobes unveils a previously undescribed bio-current fluctuation between 0 and 2.7 fA on a ∼40 min cycle. Simultaneously tracing of endogenous oscillations indicates that the bio-current waves are correlated with the periodic cellular electrokinesis. The unsynchronized electron transfer capability in the cell population results in the mean current of 0.24 fA per cell, significantly smaller than in single cells. It explains why the averaged output current of MFCs cannot reach the measured single-cell currents. This work offers a different perspective to improve the power output by extending the active episodes of the bio-current waves.

A self-powered and drug-free diabetic wound healing patch breaking hyperglycemia and low H2O2 limitations and precisely sterilizing driven by electricity.

Accelerating diabetes-related chronic wound healing is a long-sought-after goal in diabetes management. However, therapeutic strategies based on antibiotics or catalysts still face great challenges to break the limitations of antimicrobial resistance, low H2O2 and the blocking effect of bacterial biofilms on antibiotic/catalyst penetration. Herein, we reported a glucose biofuel cell-powered and drug-free antibacterial patch, which consisted of an MAF-7 protected glucose oxidase/horseradish peroxidase anode and a horseradish peroxidase cathode, for treating diabetic wounds. This self-powered patch could take high blood glucose as fuel to generate electricity and abundant reactive oxygen species (ROS) in situ, synergistically regulating local hyperglycemia and breaking the limitations of insufficient ROS caused by low H2O2 levels. In particular, the electric field created by the GBFC could drive the negatively charged bacteria to adhere firmly to the electrode surface. As a result, the ROS produced in situ on the electrodes was localized to the bacteria, realizing precise sterilization. In vivo experiments confirmed that this self-powered patch enabled the wounds on diabetic mice to take a mere 10 days to eliminate inflammation and form mature skin with new hair follicles, demonstrating its great potential in treating bacteria-infected diabetic wounds.