Cation Triggered Self-Assembly of α-Lactalbumin Nanotubes.

Metal ions play a dual role in biological systems. Although they actively participate in vital life processes, they may contribute to protein aggregation and misfolding and thus contribute to development of diseases and other pathologies. In nanofabrication, metal ions mediate the formation of nanostructures with diverse properties. Here, we investigated the self-assembly of α-lactalbumin into nanotubes induced by coordination with metal ions, screened among the series Mn2+, Co2+, Ni2+, Zn2+, Cd2+, and Au3+. Our results revealed that the affinity of metal ions toward hydrolyzed α-lactalbumin peptides not only impacts the kinetics of nanotube formation but also influences their length and rigidity. These findings expand our understanding of supramolecular assembly processes in protein-based materials and pave the way for designing novel materials such as metallogels in biochip and biosensor applications.

Ion-Induced Reassembly between Protein Nanotubes and Nanospheres.

Proteins used as building blocks to template nanostructures with manifold morphologies have been widely reported. Understanding their self-assembly and reassembly mechanism is important for designing functional biomaterials. Herein, we show that enzyme-hydrolyzed α-lactalbumin (α-lac) can self-assemble into either nanotubes in the presence of Ca2+ ions or nanospheres in the absence of Ca2+ in solution. Remarkably, such assembled α-lac nanotubes can be elongated by adding preassembled α-lac nanospheres and Ca2+ solution, which suggests that the self-assembled α-lac nanospheres undergo disassembly and reassembly processes into existing nanotube nuclei. By performing atomic force microscopy (AFM), transmission electron microscopy (TEM), and confocal laser scanning microscopy (CLSM), it indicates that there is an equilibrium among nanotubes, nanospheres, hydrolyzed α-lac, and Ca2+ in solution. The structural transition between nanotubes and nanospheres is driven from a less stable structure into a more stable structure determined by the conditions. During the transition from nanospheres into nanotubes, the hydrolyzed α-lac in nanospheres transfers into helical ribbon form at both nanotube extremities. Then helical ribbons close into mature nanotubes, extending the length of the initial nuclei. Besides, by dilution or adding ethylene glycol bis(2-aminoethyl ether) tetraacetic acid (EGTA), the decreased Ca2+ concentration in solution drives the Ca2+ dissociating from nanotubes into solution, leading to the transitions from nanotubes into nanospheres. The reversible transformation between nanotubes and nanospheres is achieved by adjusting the pH value from 7.5 to 5.0 and back to 7.5. This is because the stability of nanotubes decreases from pH 7.5 to 5 but increases from 5 to 7.5. Significantly, this approach can be used for the fabrication of various responsive nanomaterials from the same starting material.

Pyrazine as a More Efficient Luminophore than Benzene for Producing Red-Shifted and Enhanced Photoluminescence.

The development of organic photoluminescent (PL) materials with red-shifted and enhanced emissions is beneficial to promoting their applications. Luminescent materials based on aromatic heterocycles (e.g., pyrazine) usually have red-shifted and enhanced photoluminescence compared with phenyl-based luminescent materials. In this work, the photoluminescence behaviors of pyrazine and its derivatives (o-dichloro-, o-dicyano-, and dichlorodicyano-substituted) are compared with those of benzene and its derivatives. All compounds exhibit fluorescence emissions ranging from blue to yellow, and the fluorescence emissions of pyrazinyl compounds are more red-shifted than those of phenyl compounds. Except for the o-dicyano-substituted compound, pyrazinyl compounds exhibit stronger fluorescence emissions than corresponding phenyl compounds in both pure substances and ethanol solutions. In addition, both 5,6-dichloro-2,3-dicyanopyrazine (P4) and 4,5-dichloro-1,2-dicyanobenzene (B4) exhibit room temperature phosphorescence, and the maximum delayed emission wavelength is red-shifted from 575 nm of B4 to 637 nm of P4. The energy gaps between the highest occupied molecular orbital and the lowest unoccupied molecular orbital of the monomers of pyrazinyl compounds are reduced by 0.07-1.37 eV compared with the monomers of phenyl compounds, which is the fundamental reason for the red-shifted emissions of the pyrazinyl compounds. Moreover, compared to B4, the smaller molecular spacing in the P4 crystal structure facilitates interlayer electron transfer and hence the formation of more extended through-space conjugation, resulting in the red-shifted emission of P4. This work proves that pyrazine is a more efficient luminophore than benzene for constructing PL compounds with longer emission wavelengths and higher quantum yields, which are important in guiding the design and preparation of organic PL materials.

The association between different types of physical activity and smoking behavior.

BACKGROUND: Smoking is harmful, which has become a major public health burden. Physical activity may be related to smoking. Physical activity is one of the current methods for smoking control and smoking cessation. Different types of physical activity may have different effect on smoking behavior. OBJECTIVE: The purpose of this study was to identify the direction and extent of the impact of different types of physical activity above moderate intensity (including work physical activity, recreational physical activity, commuter physical activity and sedentary behavior) on smoking behavior. MATERIALS AND METHODS: In this study, a total of 2,015 individuals (1,233 males and 782 females, mean age 54.02±17.31 years) was selected from the representative population aged 20 and above in the National Health and Nutrition Survey of the United States from 2017 to 2018. Physical activity was assessed using the Global Physical Activity Questionnaire (GPAQ) ; the tobacco use questionnaire (SMQ) was used to determine whether the sample had smoking behavior at this stage. Binary Logistic regression analysis was performed with various physical activities as independent variables and smoking behavior as dependent variables. All data were analyzed through Statistical Product and Service Solutions (SPSS) 26.0. RESULTS: After adjusted for all confounding variables, physical activity at work was close to significantly associated with smoking behavior (P=0.053), odds ratio (OR) =1.135 (95%Cl: 0.999-1.289). Recreational physical activity was significantly associated with smoking behavior (P < 0.001), OR=0.729 (95%Cl: 0.639-0.832). Commuting physical activity was significantly associated with smoking behavior (P < 0.001), OR=1.214 (95%Cl:1.048-1.405). Sedentary behavior was significantly associated with smoking behavior (P < 0.001), OR=1.363 (95%Cl: 1.154-1.611). CONCLUSIONS: Given that different types of physical activity have different associations with smoking behavior. Therefore, when physical activity is used as a tobacco control measurement, it is necessary to pay attention to the type and environment of physical activity. Recreational physical activities should be appropriately increased, sedentary behavior should be reduced, and smoking prohibit environment should be expanded as far as possible to achieve better clinical intervention effects.

The association of vitamin D deficiency, age and depression in US adults: a cross-sectional analysis.

BACKGROUND: Depression is an important public health burden, its risk of occurrence is associated with vitamin D deficiency and may also increase with age, while serum vitamin D levels are closely related to age. OBJECTIVE: The purpose of this study was to evaluate whether vitamin D and age are associated with depression after adjustment for each other. MATERIALS AND METHODS: We extracted data from NHANES 2013-2018, including demographic characteristics, depression level, vitamin D level, physical activity, and body measures. A total of 15,156 adults aged 20 years or older (mean age 49.81 ± 17.67 years, 7301 males and 7855 females) were included. Depression was screened by PHQ-9. Vitamin D deficiency was defined by a serum vitamin D level < 30nmol/L. We performed binary logistic regression models to analyze the association between vitamin D, age and depression, respectively. RESULTS: Vitamin D levels were negatively associated with depression (P < 0.001). Vitamin D had a significant effect on depression (OR = 0.776, 95%CI: 0.682-0.884, P < 0.001), the effect remained significant after adjusted for confounding variables (OR = 0.761, 95%CI: 0.663-0.874, P < 0.001). Age was positively associated with depression (P < 0.001) and had a significant effect on depression (OR = 1.079, 98%CI: 1.032-1.128, P = 0.001), the effect remained significant after adjusted for confounding variables (OR = 1.092, 95%CI: 1.040-1.146, P < 0.001). Age and vitamin D levels were positively correlated (P < 0.001), and older age had a significant effect on vitamin D level (OR = 1.526, 95%CI: 1.416-1.645, P < 0.001), the effect remained significant after adjusted for confounding variables (OR = 1.371, 95%CI: 1.263-1.487, P < 0.001). In addition, the prevalence of depression was higher in females (2312/7855, 29.43%) than in males (1571/7301, 21.52%), and the difference was statistically significant (P < 0.001). CONCLUSIONS: Vitamin D deficiency and older age are both associated with higher risk of depression, while older age is a protective factor for vitamin D deficiency.

Rotation axis calibration of a 3D scanning system based on dual-turntable angle cancellation.

Rotation axis calibration is crucial for high-precision automatic point cloud stitching in turntable-based 3D scanning systems. To achieve a 360° sampling with a 2D calibrator in rotation axis calibration, this paper proposes a dual-turntable angle cancellation (DTAC) method. DTAC introduces an auxiliary turntable to keep a proper relative angle between the 3D sensor and the calibrator during the calibration process. The auxiliary turntable rotates at the same and opposite angle as the main turntable and cancels the increment of the relative angle. By projecting the feature points on the planar calibrator from real-world space to virtual calibration space, the projected points all share the same rotation axis of the main turntable. Further, a layered circle center extraction (LCCE) algorithm is applied to deal with outlier data points. The algorithm uses a two-step robust estimation strategy combining RANSAC circle fitting with a median noise filter for circle center selection. The standard ball reconstruction experiment shows that the 3D system calibrated by the method achieves a mean absolute error of 0.022 mm and root mean square error of 0.025 mm within the measurement distance of 60-70 cm. Point cloud stitching experiments of different types of objects show that our method outperforms other state-of-the-art methods in stitching accuracy. The DTAC method and LCCE algorithm can improve turntable-based 3D scanning systems.

A Portable Three-Layer Compton Camera for Wide-Energy-Range Gamma-ray Imaging: Design, Simulation and Preliminary Testing.

(1) Background: The imaging energy range of a typical Compton camera is limited due to the fact that scattered gamma photons are seldom fully absorbed when the incident energies are above 3 MeV. Further improving the upper energy limit of gamma-ray imaging has important application significance in the active interrogation of special nuclear materials and chemical warfare agents, as well as range verification of proton therapy. (2) Methods: To realize gamma-ray imaging in a wide energy range of 0.3~7 MeV, a principle prototype, named a portable three-layer Compton camera, is developed using the scintillation detector that consists of an silicon photomultiplier array coupled with a Gd3Al2Ga3O12:Ce pixelated scintillator array. Implemented in a list-mode maximum likelihood expectation maximization algorithm, a far-field energy-domain imaging method based on the two interaction events is applied to estimate the initial energy and spatial distribution of gamma-ray sources. The simulation model of the detectors is established based on the Monte Carlo simulation toolkit Geant4. The reconstructed images of a 133Ba, a 137Cs and a 60Co point-like sources have been successfully obtained with our prototype in laboratory tests and compared with simulation studies. (3) Results: The proportion of effective imaging events accounts for about 2%, which allows our prototype to realize the reconstruction of the distribution of a 0.05 µSv/h 137Cs source in 10 s. The angular resolution for resolving two 137Cs point-like sources is 15°. Additional simulated imaging of the 6.13 MeV gamma-rays from 14.1 MeV neutron scattering with water preliminarily demonstrates the imaging capability for high incident energy. (4) Conclusions: We conclude that the prototype has a good imaging performance in a wide energy range (0.3~7 MeV), which shows potential in several MeV gamma-ray imaging applications.

Noninvasive Bioluminescence Imaging of Matrix Metalloproteinase-14 Activity in Lung Cancer Using a Membrane-Bound Biosensor.

Matrix metalloproteinase-14 (MMP-14) plays a crucial role in the cancer migration and metastasis by guiding the extracellular matrix remodeling and cell motility. Despite increasing efforts have been taken to develop methodology for measuring MMP-14 expression, there is a lack of tools capable of monitoring the MMP-14 dynamic activity with high temporal and spatial resolution in living cells and animals. Here, we describe the design of Gaussia luciferase (Gluc)-based membrane-bound biosensor for efficient visualization of MMP-14 activity. The epidermal growth factor (EGF) induced significant luciferase changes in the biosensor-transfected lung cancer cells. Deletion of the transmembrane domain in the mutant biosensor or treatment with an MMP-14 inhibitor, tissue inhibitor of metalloproteinase-2 (TIMP-2), relieved the EGF-induced luciferase activation, suggesting that MMP-14 functions at the cell surface to result in luciferase changes. Moreover, utilizing this biosensor, the bioluminescence signals activated by MMP-14 enabled clear visualization of MMP-14-positive lung tumors in animal models. Our results indicated this biosensor is an effective probe for quantitatively monitoring proteolytic activities in live cells and mouse models. These findings offer the general design of biosensors as an adaptable tool for studying various membrane-anchored proteases in biological models.

Beneficial effects of abscisic acid and melatonin in overcoming drought stress in cotton (Gossypium hirsutum L.).

Pot experiments were performed to study the effects of abscisic acid (ABA) and melatonin (MT) on cotton drought tolerance and to explore their combined effects. ABA or MT spraying promoted water status and antioxidant capacity of drought-stressed leaves, which was conducive to scavenge ROS, finally increasing lint yield. However, the mitigation mechanisms of ABA and MT on drought were not identical, which were mainly manifested as: (1) ABA increased the relative water content (RWC) of drought-stressed leaves via, reducing water loss, but MT increased it via, promoting water uptake efficiency; (2) for enzymatic antioxidant system, ABA and MT might modulate different kinds of superoxide dismutase to catalyze the reduction of O2 - under drought; and (3) for ascorbic acid (AsA)-glutathione (GSH) cycle, MT increased the glutathione reductase activity in drought-stressed leaves, but ABA did not. ABA + MT spraying led to higher leaf RWC and total antioxidant capacity than single hormone under drought, leading to a lower H2 O2 level. For the enzymatic antioxidant system, single hormone treatment affected Cu/ZnSOD or MnSOD expression, but ABA + MT upregulated both genes in drought-stressed leaves. Hormones combined application also had higher CAT expression than single hormone. For AsA-GSH cycle, ABA + MT had higher dehydroascorbic acid reductase activity than single hormone, resulting in higher AsA content. Moreover, hormones combined application caused higher ascorbate peroxidase activity than single hormone, suggesting that their combination synergistically improved the ability of AsA to eliminate ROS. All these confirmed that ABA plus MT had synergistic effects on improving crop drought resistance.

Unregulated emissions from diesel engine with particulate filter using Fe-based fuel borne catalyst.

The alteration and formation of toxic compounds and potential changes in the toxicity of emissions when using after-treatment technologies have gained wide attention. Volatile organic compound (VOC), carbonyl compound and particle-phase polycyclic aromatic hydrocarbon (PAH) emissions were tested at European Steady State Cycle (ESC) to study unregulated emissions from a diesel engine with a fuel-borne catalyst and diesel particulate filter (FBC-DPF). An Fe-based fuel-borne catalyst was used for this study. According to the results, brake specific emissions of total VOCs without and with DPF were 4.7 and 4.9mg/kWh, respectively, showing a 4.3% increase. Benzene and n-undecane emissions increased and toluene emission decreased, while other individual VOC emissions basically had no change. When retrofitted with the FBC-DPF, total carbonyl compound emission decreased 15.7%, from 25.8 to 21.8mg/kWh. The two highest carbonyls, formaldehyde and acetaldehyde, were reduced from 20.0 and 3.7 to 16.5 and 3.3mg/kWh respectively. The specific reactivity (SR) with DPF was reduced from 6.68 to 6.64mg/kWh. Total particle-phase PAH emissions decreased 66.4% with DPF compared to that without DPF. However, the Benzo[a]pyrene equivalent (BaPeq) with DPF had increased from 0.016 to 0.030mg/kWh. Fluoranthene and Pyrene had the greatest decrease, 91.1% and 88.4% respectively. The increase of two- and three-ring PAHs with DPF indicates that the fuel-borne catalyst caused some gas-phase PAHs to adsorb on particles. The results of this study expand the knowledge of the effects of using a particulate filter and a Fe-based fuel-borne catalyst on diesel engine unregulated emissions.

A study on the relationship between recreational physical activity and audiovisual difficulty for older adults.

Audiovisual difficulty are especially common in older adults. Audiovisual difficulty seriously affect the quality of life of older adults in their later years. It is a top priority to find out the related factors, and to intervene and prevent them. The purpose of this study was to explore the relationship between recreational physical activities and audiovisual difficulty in older adults. We hope that older adults can reduce the risk of hearing and visual difficulty through scientific physical activity. A total of 4,886 people were sampled from the National Health and Nutrition Examination Survey (NHANES) from 2013 to 2018. Recreational physical activity was assessed through the Global Physical Activity Questionnaire (GPAQ); Hearing and visual difficulty were assessed using the Disability Questionnaire (DLQ). Chi-square test was used for categorical variables and rank sum test was used for measurement variables. P < 0.05 was considered statistically significant (bilateral test). After univariate analysis, binary Logistic regression analysis was performed with recreational physical activity as the independent variable, statistically significant demographic variable as the covariate, and hearing and visual difficulty as the dependent variable, respectively. (1) After excluding all confounding variables, recreational physical activity was significantly associated with hearing difficulty (P < 0.001), odds ratio (OR) 0.657 (95% CI 0.5899-0.733); (2) Recreational physical activity was significantly associated with visual difficulty (P < 0.001), OR 0.731 (95% CI 0.630-0.849). (1) Recreational physical activity is the protective factor of hearing difficulty in older adults; (2) Recreational physical activity is a protective factor for visual difficulty in older adults.

X 2-VLM: All-in-One Pre-Trained Model for Vision-Language Tasks.

Vision language pre-training aims to learn alignments between vision and language from a large amount of data. Most existing methods only learn image-text alignments. Some others utilize pre-trained object detectors to leverage vision language alignments at the object level. In this paper, we propose to learn multi-grained vision language alignments by a unified pre-training framework that learns multi-grained aligning and multi-grained localization simultaneously. Based on it, we present X 2-VLM, an all-in-one model with a flexible modular architecture, in which we further unify image-text pre-training and video-text pre-training in one model. X 2-VLM is able to learn unlimited visual concepts associated with diverse text descriptions. Experiment results show that X 2-VLM performs the best on base and large scale for both image-text and video-text tasks, making a good trade-off between performance and model scale. Moreover, we show that the modular design of X 2-VLM results in high transferability for it to be utilized in any language or domain. For example, by simply replacing the text encoder with XLM-R, X 2-VLM outperforms state-of-the-art multilingual multi-modal pre-trained models without any multilingual pre-training.

Comprehensive analysis of exosome gene LYPD3 and prognosis/immune cell infiltration in lung cancer.

Background: Lung cancer (LC) is a leading cause of cancer-associated mortality worldwide, with high incidence and mortality rates. Ly6/PLAUR domain containing 3 (LYPD3) is a tumorigenic and highly glycosylated cell surface protein that has been rarely reported in LC. This study aimed to explore the prognostic role and immune cell infiltration of LYPD3 in LC. Methods: We used ExoCarta, a database of exosomal proteins and RNA, to select exosomes in LC. The Tumor Immune Estimation Resource (TIMER) and Human Protein Atlas (HPA) databases were utilized to compare the expression of LYPD3 in LC. We applied Gene Expression Profiling Interactive Analysis 2 (GEPIA2) and Kaplan-Meier (KM) plotter to evaluate the prognostic prediction performance of LYPD3. Biological processes (BPs), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, and gene set enrichment analysis (GSEA) analyses were performed to illustrate the possible role of LYPD3 in LC. The correlations between LYPD3 and immune cell infiltration were explored using Tumor and Immune System Interaction Database (TISIDB), GEPIA2, and TIMER. R software was used for statistical analysis and mapping. Results: A total of 904 exosome molecules were screened in LC. Further analysis showed that the up-regulation of LYPD3 in these 904 exosome molecules was associated with poor prognosis in LC. Pan-cancer analyses revealed that the expression of LYPD3 varied in many cancers, particularly in LC. Clinical correlation analysis indicated that LYPD3 was associated with stage and T classification in LC. We observed that LYPD3 co-expression genes were associated with cell cycle, DNA replication, proteasome, and regulation of the actin cytoskeleton by GSEA. Moreover, LYPD3 was associated with immune modulators. Immunophenoscores (IPS) and IPS-CTLA4 were significantly different between the high LYPD3 group and low LYPD3 group. Additionally, the median half maximal inhibitory concentration (IC50) of bexarotene, cyclopamine, etoposide, and paclitaxel in LYPD3 high group was significantly lower than that in LYPD3 low group. Conclusions: LYPD3 is involved in many BPs of LC, such as regulating immune cell infiltration and affecting prognosis. Therefore, LYPD3 may have potential value as a biomarker for prognosis and immunotherapy in LC.

Single-cell profiling of response to neoadjuvant chemo-immunotherapy in surgically resectable esophageal squamous cell carcinoma.

BACKGROUND: The efficacy of neoadjuvant chemo-immunotherapy (NAT) in esophageal squamous cell carcinoma (ESCC) is challenged by the intricate interplay within the tumor microenvironment (TME). Unveiling the immune landscape of ESCC in the context of NAT could shed light on heterogeneity and optimize therapeutic strategies for patients. METHODS: We analyzed single cells from 22 baseline and 24 post-NAT treatment samples of stage II/III ESCC patients to explore the association between the immune landscape and pathological response to neoadjuvant anti-PD-1 combination therapy, including pathological complete response (pCR), major pathological response (MPR), and incomplete pathological response (IPR). RESULTS: Single-cell profiling identified 14 major cell subsets of cancer, immune, and stromal cells. Trajectory analysis unveiled an interesting link between cancer cell differentiation and pathological response to NAT. ESCC tumors enriched with less differentiated cancer cells exhibited a potentially favorable pathological response to NAT, while tumors enriched with clusters of more differentiated cancer cells may resist treatment. Deconvolution of transcriptomes in pre-treatment tumors identified gene signatures in response to NAT contributed by specific immune cell populations. Upregulated genes associated with better pathological responses in CD8 + effector T cells primarily involved interferon-gamma (IFNγ) signaling, neutrophil degranulation, and negative regulation of the T cell apoptotic process, whereas downregulated genes were dominated by those in the immune response-activating cell surface receptor signaling pathway. Natural killer cells in pre-treatment tumors from pCR patients showed a similar upregulation of gene expression in response to IFNγ but a downregulation of genes in the neutrophil-mediated immunity pathways. A decreased cellular contexture of regulatory T cells in ESCC TME indicated a potentially favorable pathological response to NAT. Cell-cell communication analysis revealed extensive interactions between CCL5 and its receptor CCR5 in various immune cells of baseline pCR tumors. Immune checkpoint interaction pairs, including CTLA4-CD86, TIGIT-PVR, LGALS9-HAVCR2, and TNFSF4-TNFRSF4, might serve as additional therapeutic targets for ICI therapy in ESCC. CONCLUSIONS: This pioneering study unveiled an intriguing association between cancer cell differentiation and pathological response in esophageal cancer patients, revealing distinct subgroups of tumors for which neoadjuvant chemo-immunotherapy might be effective. We also delineated the immune landscape of ESCC tumors in the context of clinical response to NAT, which provides clinical insights for better understanding how patients respond to the treatment and further identifying novel therapeutic targets for ESCC patients in the future.

RAP Vol: Robust Adversary Populations With Volume Diversity Measure.

Deep reinforcement learning (DRL) algorithms have made remarkable achievements in various fields, but they are vulnerable to changes in environment dynamics. This vulnerability easily leads to poor generalization, low performance, and catastrophic failures in unseen environments, which severely hinders the application of DRL in real-world scenarios. The robustness via adversary populations (RAP) algorithm addresses this issue by introducing a population of adversaries that perturb the protagonist. However, the low data utilization efficiency and lack of population diversity greatly limit the generalization performance. This article proposes robust adversary populations with volume diversity measure (RAP Vol) to address these drawbacks. In the proposed joint adversarial training framework, we use the training data to update all adversaries rather than only a single adversary, leading to a higher data utilization efficiency and a fast convergence speed. In the proposed population diversity iterative improvement mechanism, the vectors representing adversaries span a high-dimensional region. The volume of this region is utilized to measure and enhance population diversity via its square. The ablation experiments have verified the effectiveness of our proposed method in improving the robustness against variations in environment dynamics. Also, the influence of various factors (such as adversary population size and diversity weight) on the robustness has been investigated.

Predicting late-stage age-related macular degeneration by integrating marginally weak SNPs in GWA studies.

Introduction: Age-related macular degeneration (AMD) is a progressive neurodegenerative disease and the leading cause of blindness in developed countries. Current genome-wide association studies (GWAS) for late-stage age-related macular degeneration are mainly single-marker-based approaches, which investigate one Single-Nucleotide Polymorphism (SNP) at a time and postpone the integration of inter-marker Linkage-disequilibrium (LD) information in the downstream fine mappings. Recent studies showed that directly incorporating inter-marker connection/correlation into variants detection can help discover novel marginally weak single-nucleotide polymorphisms, which are often missed in conventional genome-wide association studies, and can also help improve disease prediction accuracy. Methods: Single-marker analysis is performed first to detect marginally strong single-nucleotide polymorphisms. Then the whole-genome linkage-disequilibrium spectrum is explored and used to search for high-linkage-disequilibrium connected single-nucleotide polymorphism clusters for each strong single-nucleotide polymorphism detected. Marginally weak single-nucleotide polymorphisms are selected via a joint linear discriminant model with the detected single-nucleotide polymorphism clusters. Prediction is made based on the selected strong and weak single-nucleotide polymorphisms. Results: Several previously identified late-stage age-related macular degeneration susceptibility genes, for example, BTBD16, C3, CFH, CFHR3, HTARA1, are confirmed. Novel genes DENND1B, PLK5, ARHGAP45, and BAG6 are discovered as marginally weak signals. Overall prediction accuracy of 76.8% and 73.2% was achieved with and without the inclusion of the identified marginally weak signals, respectively. Conclusion: Marginally weak single-nucleotide polymorphisms, detected from integrating inter-marker linkage-disequilibrium information, may have strong predictive effects on age-related macular degeneration. Detecting and integrating such marginally weak signals can help with a better understanding of the underlying disease-development mechanisms for age-related macular degeneration and more accurate prognostics.

High strength and biodegradable dielectric film with synergistic alignment of chitosan nanofibrous networks and BNNSs.

The development of biodegradable and robust dielectric capacitors with high breakdown strength and energy density are indispensable. Herein, the high strength chitosan/edge hydroxylated boron nitride nanosheets (BNNSs-OH) dielectric film was fabricated via combining the dual chemically-physically crosslinking and the drafting orientation strategy, which could induced BNNSs-OH and chitosan crosslinked network alignment within the film via covalent and hydrogen bonding interaction, leading to the comprehensive reinforcement of tensile strength from 126 to 240 MPa, the Eb from 448 to 584 MV m-1, the in-plane thermal conductivity from 1.46 to 5.95 W m-1 K-1 and energy storage density from 7.22 to 13.71 J cm-1, superior than the comprehensive evaluation of the reported polymer dielectrics. The dielectric film could be completely degraded in soil in 90 days, which opened a new path for the development of next-generation environment-friendly dielectrics with excellent mechanical and dielectric properties.

Production of gas-releasing electrolyte-replenishing Ah-scale zinc metal pouch cells with aqueous gel electrolyte.

Aqueous zinc batteries are ideal candidates for grid-scale energy storage because of their safety and low-cost aspects. However, the production of large-format aqueous Zn batteries is hindered by electrolyte consumption, hydrogen gas evolution and accumulation, and Zn dendrites growth. To circumvent these issues, here we propose an "open" pouch cell design for large-format production of aqueous Zn batteries, which can release hydrogen gas and allow the refilling of the electrolyte components consumed during cell cycling. The cell uses a gel electrolyte containing crosslinked kappa (k)-carrageenan and chitosan. It bonds water molecules and hinders their side reaction with Zn, preventing electrolyte leakage and fast evaporation. As a proof-of-concept, we report the assembly and testing of a Zn | |ZnxV2O5·nH2O multi-layer "open" pouch cell using the carrageenan/chitosan gel electrolyte, which delivers an initial discharge capacity of 0.9 Ah and 84% capacity retention after 200 cycles at 200 mA g‒1, 370 kPa and 25 °C.

Boosting with an aerosolized Ad5-nCoV elicited robust immune responses in inactivated COVID-19 vaccines recipients.

Introduction: The SARS-CoV-2 Omicron variant has become the dominant SARS-CoV-2 variant and exhibits immune escape to current COVID-19 vaccines, the further boosting strategies are required. Methods: We have conducted a non-randomized, open-label and parallel-controlled phase 4 trial to evaluate the magnitude and longevity of immune responses to booster vaccination with intramuscular adenovirus vectored vaccine (Ad5-nCoV), aerosolized Ad5-nCoV, a recombinant protein subunit vaccine (ZF2001) or homologous inactivated vaccine (CoronaVac) in those who received two doses of inactivated COVID-19 vaccines. Results: The aerosolized Ad5-nCoV induced the most robust and long-lasting neutralizing activity against Omicron variant and IFNg T-cell response among all the boosters, with a distinct mucosal immune response. SARS-CoV-2-specific mucosal IgA response was substantially generated in subjects boosted with the aerosolized Ad5-nCoV at day 14 post-vaccination. At month 6, participants boosted with the aerosolized Ad5-nCoV had remarkably higher median titer and seroconversion of the Omicron BA.4/5-specific neutralizing antibody than those who received other boosters. Discussion: Our findings suggest that aerosolized Ad5-nCoV may provide an efficient alternative in response to the spread of the Omicron BA.4/5 variant. Clinical trial registration: https://www.chictr.org.cn/showproj.html?proj=152729, identifier ChiCTR2200057278.

Cellulose ionic conductor with tunable Seebeck coefficient for low-grade heat harvesting.

Natural polymer-based thermoelectric materials are significant for sustainable development because they can be used to directly harvest heat into electricity while avoiding the utilization of petroleum-based resources. Herein, cellulose ionic conductors were fabricated by using cellulose as the hydrogel matrix and cellulose solvents as the electrolytes. p-type and n-type thermoelectric generators (TEG) based on cellulose ionic conductor were obtained, with Seebeck coefficient of 2.61 and -1.33 mV/K, due to the different interactions between quaternary ammonium cations and cellulose. The cellulose TEG-based supercapacitor showed a high specific capacitance and the ability of charging with thermal energy and powering electronic devices with a maximum power density of 0.42 mW/m2. Moreover, a flexible module-type TE harvester with 10 pairs of p-n legs was assembled for body heat harvesting, delivering a thermovoltage of 0.42 V for a temperature gradient of 13 K, enabling waste/biological heat conversion, temperature monitoring and temperature control.