Decoding Organelle Interactions: Unveiling Molecular Mechanisms and Disease Therapies.

Organelles, substructures in the cytoplasm with specific morphological structures and functions, interact with each other via membrane fusion, membrane transport, and protein interactions, collectively termed organelle interaction. Organelle interaction is a complex biological process involving the interaction and regulation of several organelles, including the interaction between mitochondria-endoplasmic reticulum, endoplasmic reticulum-Golgi, mitochondria-lysosomes, and endoplasmic reticulum-peroxisomes. This interaction enables intracellular substance transport, metabolism, and signal transmission, and is closely related to the occurrence, development, and treatment of many diseases, such as cancer, neurodegenerative diseases, and metabolic diseases. Herein, the mechanisms and regulation of organelle interactions are reviewed, which are critical for understanding basic principles of cell biology and disease development mechanisms. The findings will help to facilitate the development of novel strategies for disease prevention, diagnosis, and treatment opportunities.

NEK2 contributes to radioresistance in esophageal squamous cell carcinoma by inducing protective autophagy via regulating TRIM21.

BACKGROUND: Radiotherapy (RT) has been identified as a vital treatment for esophageal squamous cell carcinoma (ESCC), while the development of radioresistance remains a major obstacle in ESCC management. The aim of this study was to investigate the effect of NIMA-related kinase 2 (NEK2) on radioresistance in ESCC cells and to reveal potential molecular mechanisms. METHODS: Human esophageal epithelial cells (HEEC) and human ESCC cell lines were obtained from the Research Center of the Fourth Hospital of Hebei Medical University (Shijiazhuang, China). Cell Counting Kit-8 (CCK-8) and flow cytometry assays were applied to assess the proliferation ability, cell cycle, apoptosis rates, and ROS production of ESCC cells. The colony-forming assay was used to estimate the effect of NEK2 on radiosensitivity. Autophagy was investigated by western blotting analysis, GFP-mRFP-LC3 fluorescence assay, and transmission electron microscopy (TEM). RESULTS: In the present study, our results showed that NEK2 was associated with radioresistance, cell cycle arrest, apoptosis, ROS production, and survival of ESCC. NEK2 knockdown could significantly inhibit growth while enhancing radiosensitivity and ROS production in ESCC cells. Interestingly, NEK2 knockdown inhibited ESCC cell autophagy and reduced autophagic flux, ultimately reversing NEK2-induced radioresistance. Mechanistically, NEK2 bound to and regulated the stability of tripartite motif-containing protein 21 (TRIM21). The accumulation of NEK2-induced light chain 3 beta 2 (LC3B II) can be reversed by the knockdown of TRIM21. CONCLUSION: These results demonstrated that NEK2 activated autophagy through TRIM21, which may provide a promising therapeutic strategy for elucidating NEK2-mediated radioresistance in ESCC.

Preparation and properties of two-dimensional Ti2CTxMXene based on electroetching method.

The continuous advancements in wearable electronics have drawn significant attention toward 2D MXenes materials for energy storage owing to their abundant availability, adaptability, and distinctive physicochemical properties. Two unresolved concerns currently revolve around environmental pollution by F-containing etching and finite kinetics caused because of re-stacking of nanosheets. In this study, Al was electrochemically etched from porous Ti2AlC electrodes without the use of fluorine, through a selective electrochemical etching process in dilute hydrochloric acid. Subsequently, Ti2CTx MXene was vertically grown on carbon fiber (CF) substrates.The resulting Ti2CTx@CF electrodes are lightweight, thin, and flexible, exhibiting a surface capacitance of 330 mF/cm² at a constant current density of 1 mA/cm² after 2000 cycles. They display a surface capacitance retention of 96.16% and a high energy density of 45.3 µWh/cm²at a power density of 0.497 mW/cm². These metrics underscore the Ti2CTx@CF electrode's commendable multifunctionality, electrochemical performance, ion transport efficiency, and charge storage capacity. Moreover, a flexible energy storage electrode material with a high area capacity was developed by combining Ti2CTx MXene nanosheets, possessing a large specific surface area, with a flexible carbon fabric substrate. .

Curcumin simultaneously improves mitochondrial dynamics and myocardial cell bioenergy after sepsis via the SIRT1-DRP1/PGC-1α pathway.

Septic cardiomyopathy (SCM) is associated with an imbalance in mitochondrial quality and high mortality rates, with no effective treatment developed to date. Curcumin provides antioxidant, anti-inflammatory, cardiovascular, and mitochondrial protection. However, curcumin has not been confirmed to improve cardiac dysfunction in sepsis. We hypothesized that curcumin can reduce abnormal inflammatory responses by improving mitochondrial function as a novel mechanism to improve SCM. To explore this hypothesis, we used an in vivo male C57BL/6 mouse sepsis model and an in vitro model of lipopolysaccharide-stimulated HL-1 cells. The effects of curcumin on sepsis-induced cardiac dysfunction, inflammatory responses, and mitochondrial quality of cardiac cells were observed using quantitative polymerase chain reaction, western blotting, echocardiography, and transmission electron microscopy. Curcumin activated sirtuin 1 (SIRT1); increased expression of the mitochondrial biogenesis-related genes Pgc1α, Tfam, and Nrf2; reduced dynamin-related protein 1 translocation from the cytoplasm to mitochondria; and restored the mitochondrial morphology and function in cardiac cells. Accordingly, curcumin protected heart function after septic shock and alleviated the effects of SCM. SIRT1 knockdown reversed the protective effects of curcumin on mitochondria. Therefore, curcumin promotes mitochondrial biogenesis and inhibits mitochondrial fragmentation by activating SIRT1, thereby improving the mitochondrial quality and reducing oxidative stress in cardiomyocytes and sepsis-induced cardiac dysfunction. These findings provide new evidence supporting the use of curcumin to treat SCM.

Production and prediction of hydroxyl radicals in distinct redox-fluctuation zones of the Yellow River Estuary.

Hydroxyl radicals (·OH) produced in subsurface sediments play an important role in biogeochemical cycles. One of the major sources of·OH in sediments is associated with reduced compounds (e.g., iron and organic matter) oxygenation. Moreover, the properties of iron forms and dissolved organic matter (DOM) components varied significantly across redox-fluctuation zones of estuaries. However, the influence of these variations on mechanisms of·OH production in estuaries remains unexplored. Herein, sediments from riparian zones, wetlands, and rice fields in the Yellow River Estuary were collected to systematically explore the diverse mechanisms of·OH generation. Rhythmic continuous·OH production (82-730 µmol/kg) occurred throughout the estuary, demonstrating notable spatial heterogeneity. The amorphous iron form and humic-like DOM components were the key contributors to·OH accumulation in estuary wetlands and freshwater restoration wetlands, respectively. The crystalline iron form and protein-like DOM components influenced the capabilities of iron reduction and continuous·OH production. Moreover, the orthogonal partial least squares models outperformed various multivariate models in screening crucial factors and predicting the spatiotemporal production of·OH. This study provides novel insights into varied mechanisms of·OH generation within distinct redox-fluctuation zones in estuaries and further elucidates elemental behavior and contaminant fate in estuarine environments. ENVIRONMENTAL IMPLICATION: Given that estuaries serve as sinks for anthropogenic pollutants, various organic pollutants (e.g., emerging contaminants such as antibiotics) have been widely detected in estuarine environments. The production of·OH in sediments has been proven to affect the fate of contaminants. Therefore, the varied mechanisms of·OH in estuarine environments, dominated by diverse iron forms and DOM components, were explored in this study. MLR and OPLS models exhibited good performance in screening crucial factors and predicting·OH production. Our work highlights that in estuarine subsurface environments, the presence of·OH potentially leads to a natural degradation of pollutants.

Advanced detection of cervical cancer biomarkers using engineered filamentous phage nanofibers.

Cervical cancer is a major global health concern, characterized by its high incidence and mortality rates. The detection of tumor markers is crucial for managing cancer, making treatment decisions, and monitoring disease progression. Vascular endothelial growth factor (VEGF) and programmed death-ligand 1 (PDL-1) are key targets in cervical cancer therapy and valuable biomarkers in predicting treatment response and prognosis. In this study, we found that combining the measurement of VEGF and soluble PDL-1 can be used for diagnosing and evaluating the progression of cervical cancer. To explore a more convenient approach for detecting and assessing cervical cancer, we designed and prepared an engineered fd bacteriophage, a human-safe viral nanofiber, equipped with two peptides targeting VEGF and PD-L1. The dual-display phage nanofiber specifically recognizes and binds to both proteins. Utilizing this nanofiber as a novel capture agent, we developed a new enzyme-linked immunosorbent assay (ELISA) method. This method shows significantly enhanced detection sensitivity compared to conventional ELISA methods, which use either anti-VEGF or anti-PD-L1 antibodies as capture agents. Therefore, the phage dual-display nanofiber presents significant potential in detecting cancer markers, evaluating medication efficacy, and advancing immunotherapy drug development. KEY POINTS: • The combined measurement of VEGF and soluble Programmed Death-Ligand 1(sPD-L1) demonstrates an additive effect in the diagnosis of cervical cancer. Fd phage nanofibers have been ingeniously engineered to display peptides that bind to VEGF and PD-L1, enabling the simultaneous detection of both proteins within a single assay • Genetically engineered phage nanofibers, adorned with two distinct peptides, can be utilized for the diagnosis and prognosis of cancer and can be mass-produced cost-effectively through bacterial infections • Employing dual-display fd phage nanofibers as capture probes, the phage ELISA method exhibited significantly enhanced detection sensitivity compared to traditional sandwich ELISA. Furthermore, phage ELISA facilitates the detection of a single protein or the simultaneous detection of multiple proteins, rendering them powerful tools for protein analysis and diagnosis across various fields, including cancer research.

Notoginsenoside R1 improves intestinal microvascular functioning in sepsis by targeting Drp1-mediated mitochondrial quality imbalance.

CONTEXT: Sepsis can result in critical organ failure, and notoginsenoside R1 (NGR1) offers mitochondrial protection. OBJECTIVE: To determine whether NGR1 improves organ function and prognosis after sepsis by protecting mitochondrial quality. MATERIALS AND METHODS: A sepsis model was established in C57BL/6 mice using cecum ligation puncture (CLP) and an in vitro model with lipopolysaccharide (LPS, 10 µg/mL)-stimulated primary intestinal microvascular endothelial cells (IMVECs) and then determine NGR1's safe dosage. Groups for each model were: in vivo-a control group, a CLP-induced sepsis group, and a CLP + NGR1 treatment group (30 mg/kg/d for 3 d); in vitro-a control group, a LPS-induced sepsis group, and a LPS + NGR1 treatment group (4 µM for 30 min). NGR1's effects on survival, intestinal function, mitochondrial quality, and mitochondrial dynamic-related protein (Drp1) were evaluated. RESULTS: Sepsis resulted in approximately 60% mortality within 7 days post-CLP, with significant reductions in intestinal microvascular perfusion and increases in vascular leakage. Severe mitochondrial quality imbalance was observed in IMVECs. NGR1 (IC50 is 854.1 µM at 30 min) targeted Drp1, inhibiting mitochondrial translocation, preventing mitochondrial fragmentation and restoring IMVEC morphology and function, thus protecting against intestinal barrier dysfunction, vascular permeability, microcirculatory flow, and improving sepsis prognosis. DISCUSSION AND CONCLUSIONS: Drp1-mediated mitochondrial quality imbalance is a potential therapeutic target for sepsis. Small molecule natural drugs like NGR1 targeting Drp1 may offer new directions for organ protection following sepsis. Future research should focus on clinical trials to evaluate NGR1's efficacy across various patient populations, potentially leading to novel treatments for sepsis.

Substrip-based registration and automatic montaging of adaptive optics retinal images.

Precise registration and montage are critical for high-resolution adaptive optics retinal image analysis but are challenged by rapid eye movement. We present a substrip-based method to improve image registration and facilitate the automatic montaging of adaptive optics scanning laser ophthalmoscopy (AOSLO). The program first batches the consecutive images into groups based on a translation threshold and selects an image with minimal distortion within each group as the reference. Within each group, the software divides each image into multiple strips and calculates the Normalized Cross-Correlation with the reference frame using two substrips at both ends of the whole strip to estimate the strip translation, producing a registered image. Then, the software aligns the registered images of all groups also using a substrip based registration, thereby generating a montage with cell-for-cell precision in the overlapping areas of adjacent frames. The algorithm was evaluated with AOSLO images acquired in human subjects with normal macular health and patients with age-related macular degeneration (AMD). Images with a motion amplitude of up to 448 pixels in the fast scanner direction over a frame of 512 × 512 pixels can be precisely registered. Automatic montage spanning up to 22.6 degrees on the retina was achieved on a cell-to-cell precision with a low misplacement rate of 0.07% (11/16,501 frames) in normal eyes and 0.51% (149/29,051 frames) in eyes with AMD. Substrip based registration significantly improved AOSLO registration accuracy.

Marbofloxacin combined with heavy rare-earth ions makes better candidates for veterinary drugs: crystal structure and bio-activity studies.

Marbofloxacin (MB) is a newly developed fluoroquinolone antibiotic used especially as a veterinary drug. It may be regarded as the improved version of enrofloxacin owing to its antibacterial activity, enhanced bioavailability, and pharmacokinetic-pharmacodynamic (PK-PD) properties. In this study, nine heavy rare-earth ions (Y, Gd, Tb, Dy, Ho, Er, Tm, Yb, and Lu) were selected in light of their potential antibacterial activity and satisfactory biosafety to afford the corresponding rare-earth metal complexes of MB: the MB-Ln series. Their chemical structures and coordination patterns were characterized using IR spectroscopy, HRMS, TGA, and X-ray single-crystal diffraction analysis. Our results confirmed that all the MB-Ln complexes yielded the coincident coordination modes with four MB ligands coordinating to the Ln(III) center. In vitro antibacterial screening on five typical bacteria strains revealed that the MB-Ln complexes exhibited antibacterial activities comparable with MB, as indicated by the MIC/MBC values, in which Escherichia coli and Salmonella typhi were the most sensitive ones to MB-Ln. Furthermore, the MB-Ln complexes were found to be much less toxic in vivo than MB, as suggested by the evaluated LD50 (50% lethal dose) values. All the MB-Ln series complexes fell in the LD50 range of 5000-15 000 mg kg-1, while the LD50 value of MB was only 1294 mg kg-1. Furthermore, MB-Lu, as the selected representative of MB-Ln, could effectively inhibit the activity of DNA gyrase, the same as MB, suggesting the primary antibacterial mechanism of the MB-Ln series. The results demonstrated the good prospects and potential of metal-based veterinary drugs with better drug performance.

A cross-scale framework for evaluating flexibility values of battery and fuel cell electric vehicles.

Flexibility has become increasingly important considering the intermittency of variable renewable energy in low-carbon energy systems. Electrified transportation exhibits great potential to provide flexibility. This article analyzed and compared the flexibility values of battery electric vehicles and fuel cell electric vehicles for planning and operating interdependent electricity and hydrogen supply chains while considering battery degradation costs. A cross-scale framework involving both macro-level and micro-level models was proposed to compute the profits of flexible EV refueling/charging with battery degradation considered. Here we show that the flexibility reduction after considering battery degradation is quantified by at least 4.7% of the minimum system cost and enlarged under fast charging and low-temperature scenarios. Our findings imply that energy policies and relevant management technologies are crucial to shaping the comparative flexibility advantage of the two transportation electrification pathways. The proposed cross-scale methodology has broad implications for the assessment of emerging energy technologies with complex dynamics.

Low-dose Olaparib improves septic cardiac function by reducing ferroptosis via accelerated mitophagy flux.

Sepsis is a dysregulated response to infection that can result in life-threatening organ failure, and septic cardiomyopathy is a serious complication involving ferroptosis. Olaparib, a classic targeted drug used in oncology, has demonstrated potential protective effects against sepsis. However, the exact mechanisms underlying its action remain to be elucidated. In our study, we meticulously screened ferroptosis genes associated with sepsis, and conducted comprehensive functional enrichment analyses to delineate the relationship between ferroptosis and mitochondrial damage. Eight sepsis-characterized ferroptosis genes were identified in sepsis patients, including DPP4, LPIN1, PGD, HP, MAPK14, POR, GCLM, and SLC38A1, which were significantly correlated with mitochondrial quality imbalance. Utilizing DrugBank and molecular docking, we demonstrated a robust interaction of Olaparib with these genes. Lipopolysaccharide (LPS)-stimulated HL-1 cells and monocytes were used to establish an in vitro sepsis model. Additionally, an in vivo model was developed using mice subjected to cecal ligation and perforation (CLP). Intriguingly, low-dose Olaparib (5 mg/kg) effectively targeted and mitigated markers associated with ferroptosis, concurrently improving mitochondrial quality. This led to a marked enhancement in cardiac function and a significant increase in survival rates in septic mice (p < 0.05). The mechanism through which Olaparib ameliorates ferroptosis in cardiac and leukocyte cells post-sepsis is attributed to its facilitation of mitophagy, thus favoring mitochondrial integrity. In conclusion, our findings suggest that low-dose Olaparib can improve mitochondrial quality by accelerating mitophagy flux, consequently inhibiting ferroptosis and preserving cardiac function after sepsis.

Fascin actin-bundling protein 1 regulates non-small cell lung cancer progression by influencing the transcription and splicing of tumorigenesis-related genes.

Background: High mortality rates are prevalent among patients with non-small-cell lung cancer (NSCLC), and effective therapeutic targets are key prognostic factors. Fascin actin-bundling protein 1 (FSCN1) promotes NSCLC; however, its role as an RNA-binding protein in NSCLC remains unexplored. Therefore, we aimed to explore FSCN1 expression and function in A549 cells. Method: We screened for alternative-splicing events and differentially expressed genes (DEGs) after FSCN1 silence via RNA-sequencing (RNA-seq). FSCN1 immunoprecipitation followed by RNA-seq were used to identify target genes whose mRNA expression and pre-mRNA alternative-splicing levels might be influenced by FSCN1. Results: Silencing FSCN1 in A549 cells affected malignant phenotypes; it inhibited proliferation, migration, and invasion, and promoted apoptosis. RNA-seq analysis revealed 2,851 DEGs and 3,057 alternatively spliced genes. Gene ontology-based functional enrichment analysis showed that downregulated DEGs and alternatively splicing genes were enriched for the cell-cycle. FSCN1 promoted the alternative splicing of cell-cycle-related mRNAs involved in tumorigenesis (i.e., BCCIP, DLGAP5, PRC1, RECQL5, WTAP, and SGO1). Combined analysis of FSCN1 RNA-binding targets and RNA-seq data suggested that FSCN1 might affect ACTG1, KRT7, and PDE3A expression by modulating the pre-mRNA alternative-splicing levels of NME4, NCOR2, and EEF1D, that were bound to long non-coding RNA transcripts (RNASNHG20, NEAT1, NSD2, and FTH1), which were highly abundant. Overall, extensive transcriptome analysis of gene alternative splicing and expression levels was performed in cells transfected with FSCN1 short-interfering RNA. Our data provide global insights into the regulatory mechanisms associated with the roles of FSCN1 and its target genes in lung cancer.

Activated Drp1 Initiates the Formation of Endoplasmic Reticulum-Mitochondrial Contacts via Shrm4-Mediated Actin Bundling.

Excessive mitochondrial fission following ischemia and hypoxia relies on the formation of contacts between the endoplasmic reticulum and mitochondria (ER-Mito); however, the specific mechanisms behind this process remain unclear. Confocal microscopy and time course recording are used to investigate how ischemia and hypoxia affect the activation of dynamin-related protein 1 (Drp1), a protein central to mitochondrial dynamics, ER-Mito interactions, and the consequences of modifying the expression of Drp1, shroom (Shrm) 4, and inverted formin (INF) 2 on ER-Mito contact establishment. Both Drp1 activation and ER-Mito contact initiation cause excessive mitochondrial fission and dysfunction under ischemic-hypoxic conditions. The activated form of Drp1 aids in ER-Mito contact initiation by recruiting Shrm4 and promoting actin bundling between the ER and mitochondria. This process relies on the structural interplay between INF2 and scattered F-actin on the ER. This study uncovers new roles of cytoplasmic Drp1, providing valuable insights for devising strategies to manage mitochondrial imbalances in the context of ischemic-hypoxic injury.

Origin of thermally activated Er3+ emission in GeGaSe films and waveguides.

The origin of the dead or active emission from Er in various Er-doped films has been unclear. Here we took Er-doped GeGaSe as examples and investigated the correlation between the intensity of the photoluminescence (PL) spectra, the content of the activated Er ions, and the intensity of the absorption spectra in the waveguides. We found the linear correlation between the content of Er ions, photoluminescence, and absorption intensity. This provides clear evidence that thermal annealing can promote the conversion of Er metals into Er ions, and such a conversion is essential for practical applications, in which the number of the activated Er ions rather than the nominal Er contents in the materials plays an important role in achieving emission and thus effective optical amplification and lasing.

On-chip Er-doped Ta2O5 waveguide amplifiers with a high internal net gain.

We designed and fabricated a double-layered structure Er3+:Ta2O5 waveguide and investigated its optical amplification performance in C band. The pump laser threshold for zero gain at 1533 nm was 2.5 mW, and the internal net gain was ∼4.63 dB/cm for a lunched pump power of 36.1 mW at 980 nm and signal input power of -30.0 dBm (1 µW). The relationship between the internal gain and the signal input power was also investigated, and a large internal net gain of 10.58 dB/cm was achieved at a signal input power of ∼-47.1 dBm. The results confirm the potentials of the use of Ta2O5 as a host material for optical waveguide amplification.

Clinical and Genetic Study of Three Inherited Microdeletions of Chromosome 16p11.2.

Copy number variations (CNVs) in chromosome 16p11.2 are not rare. 16p11.2 microdeletion is among the most commonly known genetic etiologies of overweightness, autism spectrum disorder (ASD), and related neurodevelopmental disorders. We report the prenatal diagnosis and genetic counseling of three cases with inherited 16p11.2 microdeletions. In these families, mother/father and fetus have the same microdeletion. Following the use of molecular genetic techniques including array-based methods, the number of reported cases has rapidly increased. A combination of prenatal three-dimensional ultrasound, karyotype analysis, chromosomal microarray analysis (CMA), copy number variation sequencing (CNV-seq), whole-exome sequencing (WES), and genetic counseling is helpful for the prenatal diagnosis of chromosomal microdeletions/microduplications.

[Outcomes and measurements of randomized controlled trial for traditional Chinese medicine in treatment of endometriosis].

This study aims to analyze the outcomes and measurements of randomized controlled trial(RCT) for traditional Chinese medicine(TCM) treatment of endometriosis(EM) and provide a basis for the building of the core outcome set(COS) of EM. The RCT for TCM treatment of EM was retrieved from medical literature databases with the time interval from inception to February 3, 2022. The Cochrane risk of bias assessment tool was employed to evaluate the risk of bias of the included RCT, and descriptive analyses of the extracted information were carried out. A total of 519 RCTs were included, with the sample sizes ranging from 28-582 patients and 239 outcome indicators(8 outcome indicators per RCT on average). According to the functional properties, the reported outcome indicators were classified into 7 indicators: clinical efficacy assessment, indicators of clinical symptoms and signs, TCM symptom efficacy indicators, physical and chemical examinations, quality of life, long-term prognosis, and safety events. All the 519 RCTs had problems, such as the lack of differentiation between primary and secondary outcome indicators(1.73% RCTs reported such differen-tiation), poor quality, confused criteria for composite outcome indicators and arbitrary combination of indicators(45 criteria for the single outcome indicator of efficiency), and messy measurements(as many as 18 measurements for TCM symptom score). In addition, as a chronic disease, EM requires long-term management. The outcome indicators vary for the patients in different disease stages, such as EM pain, EM infertility, and post-operative EM, while the specific outcome indicator sets for different EM populations remain to be developed. In addition, the time point of measurement for EM long-term outcomes remains unclear, and the definition of TCM syndromes lacks standards. The RCT for TCM treatment had a variety of problems, such as the lack of differentiation of outcome indicators, confusion in criteria and measurements, lack of specific outcome indicator sets for different EM populations, and unclear time points for long-term outcomes. Therefore, the studies about COS need to be carried out urgently.

Radiotherapy combined with nano-biomaterials for cancer radio-immunotherapy.

Radiotherapy (RT) plays an important role in tumor therapy due to its noninvasiveness and wide adaptation. In recent years, radiation therapy has been discovered to induce an anti-tumor immune response, which arouses widespread concern among scientists and clinicians. In this review, we highlight recent advances in the applications of nano-biomaterials for radiotherapy-activated immunotherapy. We first discuss the combination of different radiosensitizing nano-biomaterials and immune checkpoint inhibitors to enhance tumor immune response and improve radiotherapy efficacy. Subsequently, various nano-biomaterials-enabled tumor oxygenation strategies are introduced to alleviate the hypoxic tumor environment and amplify the immunomodulatory effect. With the aid of nano-vaccines and adjuvants, radiotherapy refreshes the host's immune system. Additionally, ionizing radiation responsive nano-biomaterials raise innate immunity-mediated anti-tumor immunity. At last, we summarize the rapid development of immune modulatable nano-biomaterials and discuss the key challenge in the development of nano-biomaterials for tumor radio-immunotherapy. Understanding the nano-biomaterials-assisted radio-immunotherapy will maximize the benefits of clinical radiotherapy and immunotherapy and facilitate the development of new combinational therapy modality.

High-speed measurement of retinal arterial blood flow in the living human eye with adaptive optics ophthalmoscopy.

We present a technique to measure the rapid blood velocity in large retinal vessels with high spatiotemporal resolution. Red blood cell motion traces in the vessels were non-invasively imaged using an adaptive optics near-confocal scanning ophthalmoscope at a frame rate of 200 fps. We developed software to measure blood velocity automatically. We demonstrated the ability to measure the spatiotemporal profiles of the pulsatile blood flow with a maximum velocity of 95-156 mm/s in retinal arterioles with a diameter >100 µm. High-speed and high-resolution imaging increased the dynamic range, enhanced sensitivity, and improved the accuracy when studying retinal hemodynamics.