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.

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.

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.

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.

Adhesive Ergothioneine Hyaluronate Gel Protects against Radiation Gastroenteritis by Alleviating Apoptosis, Inflammation, and Gut Microbiota Dysbiosis.

Radiation gastroenteritis represents one of the most prevalent and hazardous complications of abdominopelvic radiotherapy, which not only severely reduces patients' life quality but also restricts radiotherapy efficacy. However, there is currently no clinically available oral radioprotector for this threatening disease due to its complex pathogenesis and the harsh gastrointestinal environment. To this end, this study developed a facile but effective oral radioprotector, ergothioneine hyaluronate (EGT@HA) gel, protecting against radiation gastroenteritis by synergistically regulating oxidative stress, inflammation, and gut microbiota. In vitro and cellular experiments verified the chemical stability and free radical scavenging ability of EGT and its favorable cellular radioprotective efficacy by inhibiting intracellular reactive oxidative species (ROS) generation, DNA damage, mitochondrial damage, and apoptosis. At the in vivo level, EGT@HA with prolonged gastrointestinal residence mitigated radiation-induced gastrointestinal tissue injury, apoptosis, neutrophil infiltration, and gut flora dysbiosis. For the first time, this work investigated the protective effects of EGT@HA gel on radiation gastroenteritis, which not only hastens the advancement of the novel gastrointestinal radioprotector but also provides a valuable gastrointestinal radioprotection paradigm by synergistically modulating oxidative stress, inflammation, and gut microbiota disturbance.

Ascidian-Inspired Temperature-Switchable Hydrogels with Antioxidant Fullerenols for Protecting Radiation-Induced Oral Mucositis and Maintaining the Homeostasis of Oral Microbiota.

A key characteristic of radiation-induced oral mucositis (RIOM) is oxidative stress mediated by the "reactive oxygen species (ROS) storm" generated from water radiolysis, resulting in severe pathological lesions, accompanied by a disturbance of oral microbiota. Therefore, a sprayable in situ hydrogel loaded with "free radical sponge" fullerenols (FOH) is developed as antioxidant agent for RIOM radioprotection. Inspired by marine organisms, 3,4,5-trihydroxyphenylalanine (TOPA) which is enriched in ascidians is grafted to clinically approved temperature-switchable Pluronic F127 to produce gallic acid (containing the TOPA fragment)-modified Pluronic F127 (MGA) hydrogels to resist the fast loss of FOH via biomimetic adhesion during oral movement and saliva erosion. Based on this, progressive RIOM found in mice is alleviated by treatment of FOH-loaded MGA hydrogels whether pre-irradiation prophylactic administration or post-irradiation therapeutic administration, which contributes to maintaining the homeostasis of oral microbiota. Mechanistically, FOH inhibits cell apoptosis by scavenging radiation-induced excess ROS and up-regulates the inherent enzymatic antioxidants, thereby protecting the proliferation and migration of mucosal epithelial cells. In conclusion, this work not only provides proof-of-principle evidence for the oral radioprotection of FOH by blocking the "ROS storm", but also provides an effective and easy-to-use hydrogel system for mucosal in situ administration.

Modeling the Breakup of Oil-Particle Aggregates in Turbulent Environments for Projectile Penetration.

After an oil spill incident, the spilled oil slicks are observed to migrate to the shoreline area. Under the turbulent conditions, they break into small droplets and are suspended in the water column. The dispersed droplets are expected to interact with the suspended particles and form the oil-particle aggregates (OPAs), which significantly changes the transport of the oil. Instead of an earlier assumption that particles cover the oil surface, thus preventing further breakage or aggregation of OPAs, recent studies demonstrated that particles act like projectiles penetrating the oil droplets, resulting in the breakage of OPAs over a longer period of time. A model looking into the OPA breakup through two breakup mechanisms was proposed for the first time. The first method depicted the breakup of one large OPA into two daughter droplets owing to the turbulent nature, while the second method demonstrated the tear of the OPA surface layer caused by particle uprooting. The model was then calibrated by an experimental study targeting crude oil with varied viscosities, along with previous experimental investigations. Three key factors were identified accounting for the breakage of OPAs, where the increase in particle concentration in the natural environment and the increase in turbulent energy of the surrounding flows benefited the breakage of OPAs, and the increase in oil viscosity suppressed the breakage due to large resistance to shear stress. Besides these elements, the impact of the particle shape on the penetration depth was discussed. The model serves as a fundamental theory to describe the evolution of OPAs for fragmentation behavior.

Mussel-Inspired Tantalum Nanocomposite Hydrogels for In Situ Oral Cancer Treatment.

Oral squamous cell carcinoma (OSCC) is one of the most common oral malignancies. Radiotherapy is the primary noninvasive treatment of OSCC for avoiding surgery-induced facial deformities and impaired oral function. However, the specificity of in situ OSCC limits radiotherapeutic effects because of the hypoxia-induced low radiosensitivity of tumors and the low radiation tolerance of surrounding normal tissues. Here, we design a highly efficient and low-toxic radiosensitization strategy. On the one hand, biocompatible poly(vinyl pyrrolidone)-modified tantalum nanoparticles (Ta@PVP NPs) not only have strong X-ray deposition capability to upregulate oxidative stress but also have photothermal conversion efficiency to improve hypoxia for tumor radiosensitivity. On the other hand, to optimize the spatial distribution of Ta@PVP NPs within tumors, mussel-inspired catechol with bioadhesive properties is grafted on tumor microenvironment-responsive sodium alginate (DAA) to form in situ hydrogels for precision radiotherapy. On this basis, we find that Ta@PVP-DAA hydrogels effectively inhibit OSCC development in mice under photothermal-assisted radiotherapy without facial deformities and damage to surrounding normal tissues. Overall, our work not only promotes the exploration of Ta@PVP NPs as new radiosensitizers for OSCC but also develops a nanocomposite hydrogel system strategy as a promising paradigm for the precision treatment of orthotopic tumors.

Oil Transport Following the Deepwater Horizon Blowout.

The Deepwater Horizon oil spill in the Gulf of Mexico in 2010 was the largest in US history, covering more than 1,000 km of shorelines and causing losses that exceeded $50 billion. While oil transformation processes are understood at the laboratory scale, the extent of the Deepwater Horizon spill made it challenging to integrate these processes in the field. This review tracks the Deepwater Horizon oil during its journey from the Mississippi Canyon block 252 (MC252) wellhead, first discussing the formation of the oil and gas plume and the ensuing oil droplet size distribution, then focusing on the behavior of the oil on the water surface with and without waves. It then reports on massive drifter experiments in the Gulf of Mexico and the impact of the Mississippi River on the oil transport. Finally, it concludes by addressing the formation of oil-particle aggregates. Although physical processes lend themselves to numerical modeling, we attempted to elucidate them without using advanced modeling, as our goal is to enhance communication among scientists, engineers, and other entities interested in oil spills.

Mechanism of astragalus injection to relieve symptoms of preeclampsia rat model by inhibiting MMP-9/sFlt-1/TNF-α.

Objective: The aim of this study was to observe the effect of astragalus injection on rats with preeclampsia. Methods: A total of 30 pregnant Sprague Dawley (SD) rats were randomly assigned to the model group (MG), the astragalus group (AG) or the control group (CG), with 10 rats in each group. The rat model of preeclampsia was established by subcutaneous injection of 50 mg/(kg∙d) of N-nitro-L-arginine methyl ester (L-NAME), and 0.024 ml/(g∙d) astragalus injection was administered intraperitoneally. The arterial pressure, urinary protein, placental mass, fetal weight, inflammatory factors in peripheral blood of pregnant rats, protein and mRNA levels of nuclear factor- κB (NF-κB), matrix metalloproteinase-9 (MMP-9), nuclear transcription factor 5 (NFAT-5), placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1), and reactive oxygen species (ROS) activity, malondialdehyde (MDA) and nitric oxide (NO) levels in placental tissues were compared in the 3 groups. Results: After treatment, the arterial pressure and urinary protein levels in pregnant rats in the MG group were significantly higher than in the CG and AG groups (P < .05). The placental mass in the MG group was lower than in the CG and AG groups (P < .05). The messenger RNA (mRNA) and protein levels of sFlt-1, NFAT-5 and NF-κB, as well as ROS activity, MDA, inerleukin (IL)-6, tumor necrosis factor alpha (TNF-α) and interferon gamma (INF-γ) in the AG group were significantly lower than in the MG group, and mRNA and protein expression of MMP-9 and PlGF, as well as the NO level in the AG group, were significantly higher than in the MG (P < .05). Conclusions: Astragalus injection can effectively inhibit the expression of sFlt-1, NFAT-5, NF-κB and enhance the expression of PlGF and MMP-9 in the placental tissue of rats with preeclampsia, which may be the mechanism of preeclampsia treatment.

Research Progress on the Biological Activities of Metal Complexes Bearing Polycyclic Aromatic Hydrazones.

Due to the abundant and promising biological activities of aromatic hydrazones, it is of great significance to study the biological activities of their metal complexes for the research and development of metal-based drugs. In this review, we focus on the metal complexes of polycyclic aromatic hydrazones, which still do not receive much attention, and summarize the studies related to their biological activities. Although the large number of metal complexes in phenylhydrazone prevent them all from being summarized, the significant value of polycyclic aromatic hydrocarbons themselves (such as naphthalene and anthracene) as pharmacophores are also considered. Therefore, the bioactivities of the metal complexes of naphthylhydrazone and anthrahydrazone are focused on, and the recent research progress on the metal complexes of anthrahydrazone by the authors is also included. In terms of biological activities, these complexes mainly show antibacterial and anticancer activities, along with less bioactivities. The present review demonstrates that the structural design and bioactivities of these complexes are fundamental, which also indicates a certain structure-activity relationship (SAR) in some substructural areas. However, a systematic and comprehensive conclusion of the SAR is still not available, which suggests that more attention should be paid to the bioactivities of the metal complexes of polycyclic aromatic hydrazones since their potential in structural design and biological activity remains to be explored. We hope that this review will attract more researchers to devote their interest and energy into this promising area.

The diagnostic significance of blood-derived circRNAs in NSCLC: Systematic review and meta-analysis.

Background: Using blood-derived circular RNAs (circRNAs) may be an efficient tool for noninvasive fluid biopsy in diagnosing non-small cell lung cancer (NSCLC). However, no relevant systemic meta-analysis has been conducted so far to support the diagnostic value of using blood-derived circRNAs in NSCLC clinically. The aim of this study is to clarify the issue through a meta-analysis. Methods: A systematic search strategy was used to search relevant literature in the databases of PubMed, Web of Science, and Cochrane Library from 2017 to 2022. The relationship between the diagnostic accuracy of circRNAs and NSCLC was analyzed. For the purpose of evaluating the quality of the literature, Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) was used. Statistical analyses were assessed using Stata software (version 17.0) and META-DISC (version 1.4). Results: The meta-analysis included 1,093 patients with NSCLC and 959 controls. Results are as follows: pooled sensitivity, 0.78 (95% CI = 0.71-0.83, I2 = 71.86); pooled specificity, 0.76 (95% CI = 0.70-0.82, I2 = 70.12); pooled positive likelihood ratio (PLR), 3.3 (95% CI = 2.6-4.2, I2 = 37.56); pooled negative likelihood ratio (NLR), 0.29 (95% CI = 0.23-0.37, I2 = 64.67); diagnostic odds ratio (DOR), 11.42 (95% CI = 7.88-16.56, I2 = 99.05); area under the receiver operating characteristic curve (AUC), 0.84 (95% CI = 0.80-0.87). Based on the subgroup analysis, it appears that the heterogeneity is primarily caused by the NSCLC subgroup. Conclusion: circRNAs are highly useful diagnostic biomarkers for NSCLC in China. Further prospective studies on the diagnostic value of circRNAs should be conducted in multiple countries. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022323804.

Engineering Single-Atom Iron Nanozymes with Radiation-Enhanced Self-Cascade Catalysis and Self-Supplied H2O2 for Radio-enzymatic Therapy.

Single-atom nanozymes (SAzymes), with individually isolated metal atom as active sites, have shown tremendous potential as enzyme-based drugs for enzymatic therapy. However, using SAzymes in tumor theranostics remains challenging because of deficient enzymatic activity and insufficient endogenous H2O2. We develop an external-field-enhanced catalysis by an atom-level engineered FeN4-centered nanozyme (FeN4-SAzyme) for radio-enzymatic therapy. This FeN4-SAzyme exhibits peroxidase-like activity capable of catalyzing H2O2 into hydroxyl radicals and converting single-site FeII species to FeIII for subsequent glutathione oxidase-like activity. Density functional theory calculations are used to rationalize the origin of the single-site self-cascade enzymatic activity. Importantly, using X-rays can improve the overall single-site cascade enzymatic reaction process via promoting the conversion frequency of FeII/FeIII. As a H2O2 producer, natural glucose oxidase is further decorated onto the surface of FeN4-SAzyme to yield the final construct GOD@FeN4-SAzyme. The resulting GOD@FeN4-SAzyme not only supplies in situ H2O2 to continuously produce highly toxic hydroxyl radicals but also induces the localized deposition of radiation dose, subsequently inducing intensive apoptosis and ferroptosis in vitro. Such a synergistic effect of radiotherapy and self-cascade enzymatic therapy allows for improved tumor growth inhibition with minimal side effects in vivo. Collectively, this work demonstrates the introduction of external fields to enhance enzyme-like performance of nanozymes without changing their properties and highlights a robust therapeutic capable of self-supplying H2O2 and amplifying self-cascade reactions to address the limitations of enzymatic treatment.

Identification of MMP9 as a Novel Biomarker to Mitochondrial Metabolism Disorder and Oxidative Stress in Calcific Aortic Valve Stenosis.

Calcific aortic valve stenosis (CAVS) is the most common heart valve disorder among humans. To date, no effective method has been identified to prevent this disease. Herein, we aimed to identify novel diagnostic and mitochondria-related biomarkers of CAVS, based on two machine learning algorithms. We further explored their association with infiltrating immune cells and studied their potential function in CAVS. The GSE12644, GSE51472, and GSE83453 expression profiles were downloaded from the Gene Expression Omnibus (GEO) repository. The GSE12644 and GSE51472 datasets were integrated to identify differentially expressed genes (DEGs). GSE12644 contains 10 normal and 10 CAVS samples, whereas GSE51472 contains 5 normal and 10 CAVS samples. GO and KEGG assays of DEGs were conducted, and the correlation between matrix metalloproteinase 9 (MMP9) expression and immune cell infiltration was explored, using CIBERSORT. The LASSO regression model and SVM-RFE analysis were used to identify diagnostic genes. The expression of MMP9 in CAVS and non-CAVS samples was measured using RT-PCR, western blotting and immunohistochemistry. A series of functional experiments were performed to explore the potential role of MMP9 in mitochondrial metabolism and oxidative stress during CAVS progression. Twenty-two DEGs were identified, of which six genes (SCG2, PPBP, TREM1, CCL19, WIF1, and MMP9) were ultimately distinguished as diagnostic genes in CAVS. Of these, MMP9 was indicated as a mitochondria-related gene, the expression and diagnostic value of which were further confirmed in the GSE83453 dataset. Correlation analysis revealed a positive correlation between MMP9 and infiltrating immune cells. In our cohort, MMP9 expression was distinctly increased in CAVS samples, and its inhibition attenuated the calcification of valve interstitial cells (VICs) by suppressing mitochondrial damage and oxidative stress. Taken together, our findings suggest MMP9 as a novel mitochondrial dysfunction biomarker and therapeutic target for CAVS.

Development of an offshore response guidance tool for determining the impact of SSDI on released gas and benzene from artificial subsea oil well blowout simulations.

We present an analysis of 2225 simulations of artificial oil well blowouts in nearshore and offshore waters of Newfoundland, Canada. In the simulations, we coupled the VDROP-J and TAMOC models to simulate the fate and transport of oil and gas from the release to the sea surface. Simulations were conducted with and without subsea dispersant injection. We analyzed the simulation database to quantify the mass fraction of oil and gas that surfaces, the mass fraction of released benzene that surfaces, and the horizontal offset to the surfacing zone. These data are also synthesized to yield empirical correlations to predict these output metrics from key input parameters. These correlations are summarized in an excel spreadsheet that allows rapid evaluation of spill dynamics with minimal initial knowledge of spill details. We call this tool an offshore response guidance table, which allows exploration of spill dynamics under diverse spill and response options.

Biocompatible Tantalum Nanoparticles as Radiosensitizers for Enhancing Therapy Efficacy in Primary Tumor and Metastatic Sentinel Lymph Nodes.

Metastasis of breast carcinoma is commonly realized through lymphatic circulation, which seriously threatens the lives of breast cancer patients. Therefore, efficient therapy for both primary tumor and metastatic sentinel lymph nodes (SLNs) is highly desired to inhibit cancer growth and metastasis. During breast cancer treatment, radiotherapy (RT) is a common clinical method. However, the efficacy of RT is decreased by the radioresistance to a hypoxic microenvironment and inevitable side effects for healthy issues at high radiation doses. Considering the above-mentioned, we provide high biocompatible poly(vinylpyrrolidone) coated Ta nanoparticles (Ta@PVP NPs) for photothermal therapy (PTT) assisted RT for primary tumor and metastatic SLNs. On the one hand, for primary tumor treatment, Ta@PVP NPs with a high X-ray mass attenuation coefficient (4.30 cm2/kg at 100 keV) can deposit high radiation doses within tumors. On the other hand, for metastatic SLNs treatment, the effective delivery of Ta@PVP NPs from the primary tumor into SLNs is monitored by computed tomography and photoacoustic imaging, which greatly benefit the prognosis and treatment for metastatic SLNs. Moreover, Ta@PVP NPs-mediated PTT could enhance the RT effect, and immunogenic cell death caused by RT/PTT could induce an immune response to improve the therapeutic effect of metastatic SLNs. This study not only explores the potential of Ta@PVP NPs as effective radiosensitizers and photothermal agents for combined RT and PTT but also offers an efficient strategy to cure both primary tumor and metastatic SLNs in breast carcinoma.

Noninvasive Measurement of Oxygen Saturation in Human Retinal Blood Vessels and Tissues With Multispectral Confocal Imaging.

BACKGROUND AND OBJECTIVE: Proof of concept for the first system of noninvasive human retinal vessel and tissue oxygenation measurement in axial and radial directions. MATERIALS AND METHODS: A confocal imaging system capable of calculating and mapping relative retinal blood oxygenation in radial and axial directions from three eyes of two healthy subjects was built. The relationship between oxygenation and retinal depth in vivo was analyzed to illustrate application of this novel system. RESULTS: The system shows capacity for measuring oxygenation along retinal depth for the first time. (1) Arteriovenous oxygenation difference decreases with blood vessel diameter. (2) Artery-tissue oxygenation difference is greater than vein-tissue oxygenation difference in the same region. (3) Intravascular-extravascular oxygenation difference decreases with blood vessel diameter. (4) Oxygenation data reported with a 95% CI are as follows: A1 91.5% ± 18.2%, V1 32.8% ± 18.6%, A2 97.3% ± 17.8%, V2 64.4% ± 11.2%, A3 73.2% ± 19.1%, V3 52.9% ± 15.3%, and Tissue 56.6% ± 00.4%. CONCLUSION: This article demonstrates proof of concept for retinal oxygenation calculation in radial and axial dimensions for the first time. Initial results provide biological validity to this method. Future aims include further characterization of this system's results in healthy subjects and subsequent comparison of oxygenation between diseased and healthy retinae. [Ophthalmic Surg Lasers Imaging Retina. 2022;53:275-283.].

[Transvertebral space and under the pedicle osteotomy for thoracolumbar kyphosis caused by old osteoporotic vertebral compression fracture].

Objective: To investigate the effectiveness of transvertebral space and under the pedicle osteotomy for thoracolumbar kyphosis caused by old osteoporotic vertebral compression fracture (OVCF). Methods: The clinical data of 11 patients with thoracolumbar kyphosis caused by old OVCF treated by transvertebral space and under the pedicle osteotomy between January 2016 and December 2020 were retrospectively analyzed. There were 2 males and 9 females, with an average age of 61.3 years (range, 50-77 years) and with a median disease duration of 8 years (range, 6 months to 50 years). Fracture reasons: 9 cases had a clear history of trauma, and 2 cases had no obvious incentive. A total of 11 vertebrae was involved in fracture, including T 12 in 3, L 1 in 7, L 2 in 1. The operation time, intraoperative blood loss, postoperative drainage volume, and complications were recorded. Full-length X-ray films of spine and local X-ray films of the operation area were examined before operation, at 7 days after operation, and at last follow-up. The Cobb angle of thoracolumbar kyphosis was measured, and the correction rate was calculated. The visual analogue scale (VAS) score and Oswestry disability index (ODI) were recorded to assess patients' pain and functional improvement before operation, at 1 month after operation, and at last follow-up. Results: All operations were successfully completed. The average operation time was 188.6 minutes (range, 140-215 minutes); the average intraoperative blood loss was 268.2 mL (range, 100-500 mL); the average postoperative drainage volume was 615.5 mL (range, 160-1 500 mL). One patient developed bilateral thigh rebound pain after operation, which relieved after symptomatic treatment of nutritional nerve and acesodyne. All patients were followed up 14.7 months on average (range, 6-56 months). At last follow-up, osseous fusion was observed in all patients, and no fracture, loose, or displacement of internal fixator was observed on imaging. At 7 days after operation and at last follow-up, the Cobb angle of thoracolumbar kyphosis significantly improved when compared with preoperative one ( P<0.05), and there was no significant difference between at 7 days after operation and at last follow-up ( P>0.05); the correction rates of Cobb angle at 7 days after operation and at last follow-up were 68.0%±9.8% and 60.3%±11.9%, respectively. At 1 month after operation and at last follow-up, the VAS score and ODI significantly improved when compared with preoperative ones, and further improved at last follow-up when compared with those at 1 month after operation, all showing significant differences ( P<0.05). Conclusion: Transvertebral space and under the pedicle osteotomy is an effective way to treat thoracolumbar kyphosis caused by old OVCF with less trauma, shorter operation time, and less intraoperative blood loss. Patients can obtain good orthopedic results and quality of life.