GSDMD/Drp1 signaling pathway mediates hippocampal synaptic damage and neural oscillation abnormalities in a mouse model of sepsis-associated encephalopathy.

BACKGROUND: Gasdermin D (GSDMD)-mediated pyroptotic cell death is implicated in the pathogenesis of cognitive deficits in sepsis-associated encephalopathy (SAE), yet the underlying mechanisms remain largely unclear. Dynamin-related protein 1 (Drp1) facilitates mitochondrial fission and ensures quality control to maintain cellular homeostasis during infection. This study aimed to investigate the potential role of the GSDMD/Drp1 signaling pathway in cognitive impairments in a mouse model of SAE. METHODS: C57BL/6 male mice were subjected to cecal ligation and puncture (CLP) to establish an animal model of SAE. In the interventional study, mice were treated with the GSDMD inhibitor necrosulfonamide (NSA) or the Drp1 inhibitor mitochondrial division inhibitor-1 (Mdivi-1). Surviving mice underwent behavioral tests, and hippocampal tissues were harvested for histological analysis and biochemical assays at corresponding time points. Haematoxylin-eosin staining and TUNEL assays were used to evaluate neuronal damage. Golgi staining was used to detect synaptic dendritic spine density. Additionally, transmission electron microscopy was performed to assess mitochondrial and synaptic morphology in the hippocampus. Local field potential recordings were conducted to detect network oscillations in the hippocampus. RESULTS: CLP induced the activation of GSDMD, an upregulation of Drp1, leading to associated mitochondrial impairment, neuroinflammation, as well as neuronal and synaptic damage. Consequently, these effects resulted in a reduction in neural oscillations in the hippocampus and significant learning and memory deficits in the mice. Notably, treatment with NSA or Mdivi-1 effectively prevented these GSDMD-mediated abnormalities. CONCLUSIONS: Our data indicate that the GSDMD/Drp1 signaling pathway is involved in cognitive deficits in a mouse model of SAE. Inhibiting GSDMD or Drp1 emerges as a potential therapeutic strategy to alleviate the observed synaptic damages and network oscillations abnormalities in the hippocampus of SAE mice.

Potential of semen coicis in enhancing the anti-tumor effects of PD-1 inhibitor on A549 cell lines by blocking the PI3K-AKT-mTOR pathway.

BACKGROUND: The objective of this research was to investigate how the combination of semen coicis extract and PD-1 inhibitors can potentially work together to enhance the anti-tumor effects, with a focus on understanding the underlying mechanism. METHODS: We obtained the active components and specific targets of semen coicis in the treatment of NSCLC from various databases, namely TCMSP, GeneCard, and OMIM. By utilizing the STRING database and Cytoscape software, we established a protein interaction network (PPI) for the active ingredient of semen coicis and the target genes related to NSCLC. To explore the potential pathways involved, we conducted gene ontology (GO) and biological pathway (KEGG) enrichment analyses, which were further supported by molecular docking technology. Additionally, we conducted cyto-inhibition experiments to verify the inhibitory effects of semen coicis alone or in combination with a PD-1 inhibitor on A549 cells, along with examining the associated pathways. Furthermore, we investigated the synergistic mechanism of these two drugs through cytokine release experiments and the PD-L1 expression study on A549 cells. RESULTS: Semen coicis contains two main active components, Omaine and (S)-4-Nonanolide. Its primary targets include PIK3R1, PIK3CD, PIK3CA, AKT2, and mTOR. Molecular docking experiments confirmed that these ingredients and targets form stable bonds. In vitro experiments showed that semen coicis demonstrates inhibitory effects against A549 cells, and this effect was further enhanced when combined with PD-1 inhibitors. PCR and WB analysis confirmed that the inhibition of the PI3K-AKT-mTOR pathway may contribute to this effect. Additionally, semen coicis was observed to decrease the levels of IFN-γ, IL-6, and TNF-α, promoting the recovery of the human anti-tumor immune response. And semen coicis could inhibit the induced expression of PD­L1 of A549 cells stimulated by IFN­Î³ as well. CONCLUSION: Semen coicis not only has the ability to kill tumor cells directly but also alleviates the immunosuppression found in the tumor microenvironment. Additionally, it collaboratively enhances the effectiveness of PD-1 inhibitors against tumors by blocking the activation of PI3K-AKT-mTOR.

Quantitative systems pharmacology modeling of HER2-positive metastatic breast cancer for translational efficacy evaluation and combination assessment across therapeutic modalities.

HER2-positive (HER2+) metastatic breast cancer (mBC) is highly aggressive and a major threat to human health. Despite the significant improvement in patients' prognosis given the drug development efforts during the past several decades, many clinical questions still remain to be addressed such as efficacy when combining different therapeutic modalities, best treatment sequences, interindividual variability as well as resistance and potential coping strategies. To better answer these questions, we developed a mechanistic quantitative systems pharmacology model of the pathophysiology of HER2+ mBC that was extensively calibrated and validated against multiscale data to quantitatively predict and characterize the signal transduction and preclinical tumor growth kinetics under different therapeutic interventions. Focusing on the second-line treatment for HER2+ mBC, e.g., antibody-drug conjugates (ADC), small molecule inhibitors/TKI and chemotherapy, the model accurately predicted the efficacy of various drug combinations and dosing regimens at the in vitro and in vivo levels. Sensitivity analyses and subsequent heterogeneous phenotype simulations revealed important insights into the design of new drug combinations to effectively overcome various resistance scenarios in HER2+ mBC treatments. In addition, the model predicted a better efficacy of the new TKI plus ADC combination which can potentially reduce drug dosage and toxicity, while it also shed light on the optimal treatment ordering of ADC versus TKI plus capecitabine regimens, and these findings were validated by new in vivo experiments. Our model is the first that mechanistically integrates multiple key drug modalities in HER2+ mBC research and it can serve as a high-throughput computational platform to guide future model-informed drug development and clinical translation.

Injectable Nano-Micro Composites with Anti-bacterial and Osteogenic Capabilities for Minimally Invasive Treatment of Osteomyelitis.

The effective management of osteomyelitis remains extremely challenging due to the difficulty associated with treating bone defects, the high probability of recurrence, the requirement of secondary surgery or multiple surgeries, and the difficulty in eradicating infections caused by methicillin-resistant Staphylococcus aureus (MRSA). Hence, smart biodegradable biomaterials that provide effective and precise local anti-infection effects and can promote the repair of bone defects are actively being developed. Here, a novel nano-micro composite is fabricated by combining calcium phosphate (CaP) nanosheets with drug-loaded GelMA microspheres via microfluidic technology. The microspheres are covalently linked with vancomycin (Van) through an oligonucleotide (oligo) linker using an EDC/NHS carboxyl activator. Accordingly, a smart nano-micro composite called "CaP@MS-Oligo-Van" is synthesized. The porous CaP@MS-Oligo-Van composites can target and capture bacteria. They can also release Van in response to the presence of bacterial micrococcal nuclease and Ca2+, exerting additional antibacterial effects and inhibiting the inflammatory response. Finally, the released CaP nanosheets can promote bone tissue repair. Overall, the findings show that a rapid, targeted drug release system based on CaP@MS-Oligo-Van can effectively target bone tissue infections. Hence, this agent holds potential in the clinical treatment of osteomyelitis caused by MRSA.

The role of radiotherapy in tumor immunity and the potential of PET/CT in detecting the expression of PD-1/PD-L1.

Upregulation of PD-1/PD-L1 allows cancer cells to escape from host immune systems by functionally inactivating T-cell immune surveillance. Clinical blockade strategies have resulted in an increased prevalence of patients with late-stage cancers. However, many cancer patients had limited or no response to current immunotherapeutic strategies. Therefore, how to improve the sensitivity of immunotherapy has become the focus of attention of many scholars. Radiotherapy plays a role in the recruitment of T cells in the tumor microenvironment, increases CD4 + and CD8 + T cells, and increases PD-L1 expression, resulting in the synergistically enhanced antitumor effect of irradiation and PD-L1 blockade. Radiotherapy can cause changes in tumor metabolism, especially glucose metabolism. Tumor glycolysis and tumor immune evasion are interdependent, glycolytic activity enhances PD-L1 expression on tumor cells and thus promotes anti-PD-L1 immunotherapy response. Therefore, the mechanism of radiotherapy affecting tumor immunity may be partly through intervention of tumor glucose metabolism. Furthermore, some authors had found that the uptake of 2'-deoxy-2'-[18F]fluoro-D-glucose(18F-FDG) was correlated with PD-1/PD-L1 expression. Positron emission tomography/computed tomography (PET/CT) is a non-invasive detection method for PD-1/PD-L1 expression and has several potential advantages over immunohistochemical (IHC), PET/CT can dynamically reflect the expression of PD-1/PD-L1 inside the tumor and further guide clinical treatment.

Molybdenum Nanodots for Acute Lung Injury Therapy.

Acute respiratory disease syndrome (ARDS) is a common critical disease with high morbidity and mortality rates, yet specific and effective treatments for it are currently lacking. ARDS was especially apparent and rampant during the COVID-19 pandemic. Excess reactive oxygen species (ROS) production and an uncontrolled inflammatory response play a critical role in the disease progression of ARDS. Herein, we developed molybdenum nanodots (MNDs) as a functional nanomaterial with ultrasmall size, good biocompatibility, and excellent ROS scavenging ability for the treatment of acute lung injury (ALI). MNDs, which were administered intratracheally, significantly ameliorated lung oxidative stress, inflammatory response, protein permeability, and histological severity in ALI mice without inducing any safety issues. Importantly, transcriptomics analysis indicated that MNDs protected lung tissues by inhibiting the activation of the Nod-like receptor protein 3 (NLRP3)-dependent pyroptotic pathway. This work presents a promising therapeutic agent for patients suffering from ARDS.

Surgical treatment of mixed cervical spondylosis with spontaneous cerebrospinal fluid leakage: A case report.

BACKGROUND: Spontaneous cerebrospinal fluid (CSF) leaks associated with cervical spondylosis are rare. To our knowledge, only a few cases have been reported in which treatment is challenging and varies from case to case. Here, we review the literature and describe the surgical treatment of a 70-year-old woman who presented with a CSF leak due to a cervical spine spur. CASE SUMMARY: A 70-year-old female patient who was treated for a cerebral infarction, presented with complains of weakness in the right lower extremity and a feeling of stepping on cotton. The patient underwent regular neck massage and presented with neck and right shoulder pain radiating to the right upper extremity one-month ago. Magnetic resonance imaging showed a strip of leaking cerebrospinal fluid posterior to the C1-4 vertebrae, and computed tomography showed a "sickle-shaped" disc prolapse with calcification in C4/5. We chose to perform an anterior cervical discectomy. When the prolapsed C4/5 disc was scraped, clear fluid leakage was observed, and exploration revealed a 1 mm diameter rupture in the anterior aspect of the dura mater, which was compressed continuously with cotton patties, with no significant cerebrospinal fluid leakage after 1 h. CONCLUSION: Three months after surgery, the patient was asymptomatic and follow-up imaging demonstrated complete resolution.

Marixanthotalea marina gen. nov., sp. nov., a bacterium in the family Flavobacteriaceae isolated from seawater.

A Gram-stain-negative, yellow-pigmented, non-motile, rod-shaped, catalase-positive, strictly aerobic marine bacterium, designated XHP0103T, was isolated from seawater collected from the southern Yellow Sea, PR China (34° 45' 53″ N 119° 25' 30″ E). Strain XHP0103T grew optimally at 28 °C, pH 7.5 and in 1.0-3.0 % (w/v) sea salt. MK-6 was the major respiratory quinone. The major cellular fatty acids (>10%) were iso-C15 : 0, iso-C15 : 1 G and iso-C17 : 0 3-OH. The polar lipid profile contained phosphatidylethanolamine, an unidentified aminolipid, an unidentified glycolipid and an unidentified lipid. Results of 16S rRNA gene sequence analysis indicated that strain XHP0103T displayed highest sequence similarity to Aestuariibaculum marinum IP7T (94.1 %). However, the phylogenetic trees based on 16S rRNA gene sequences suggested that strain XHP0103T clustered with Tamlana crocina HST1-43T (93.4 % sequence similarity) and Aestuariivivens insulae AH-MY3T (93.5 %). Genome sequencing revealed that strain XHP0103T comprised 3 134 388 bp with 2770 protein-coding genes, and the DNA G+C content was 35.5 %. The average nucleotide identity and digital DNA-DNA hybridization values between strain XHP0103T and T. crocina HST1-43T were 73.6 and 17.3 %, respectively. Based on phylogenetic, phenotypic, genomic and chemotaxonomic evidence, strain XHP0103T represents a novel genus in the family Flavobacteriaceae, for which the name Marixanthotalea marina gen. nov., sp. nov. is proposed. The type strain is XHP0103T (=MCCC 1K06060T=JCM 34682T).

A general method for endowing hydrophobic nanoparticles with water dispersion abilities.

Inorganic nanoparticles with long-chain ligands are usually hydrophobic. However, simple and practical methods for converting hydrophobic nanoparticles to hydrophilic nanoparticles are still lacking. Herein, we developed a general method involving using dimercaptosuccinic acid (DMSA) for endowing hydrophobic nanoparticles with water dispersion abilities. By mixing a tetrahydrofuran solution of DMSA with a cyclohexane solution of hydrophobic nanoparticles, the long-chain ligands were replaced with DMSA, with the replacement due to the strong and broad-spectrum coordination abilities of sulphydryls and carboxyls. Four representative kinds of hydrophobic nanoparticles, namely Ag, NaGdF4, TiO2, and ZnS nanoparticles, were selected for verifying the performance of this DMSA-based modification method. Meanwhile, this method can also widen the applications of hydrophobic nanoparticles and facilitate their being subjected to further graft modifications. We hope that our research will increase the chances for applications of nanomaterials to be made.

A global assessment of incidence trends of autoimmune diseases from 1990 to 2019 and predicted changes to 2040.

AIM: To analyze the global incidence trends for four autoimmune diseases (ADs) including rheumatoid arthritis (RA), inflammatory bowel disease (IBD), multiple sclerosis (MS) and psoriasis from 1990 to 2019, and further predict their changes to 2040 at global, regional, and national levels. METHODS: The estimates and 95% uncertainty intervals (UIs) for case number and agestandardized incidence rate (ASIR) of RA, IBD, MS and psoriasis were derived from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. Estimated annual percentage change (EAPC) was utilized to quantify the global incidence trends for RA, IBD, MS and psoriasis from 1990 to 2019. Furthermore, a log-linear age-period-cohort model was adopted to predict the new case number and incidence rates for these four ADs through 2040. RESULTS: From 1990 to 2019, the global ASIR rose significantly for RA (EAPC = 0.30%, 95% CI: 0.26 to 0.34) whereas declined significantly for IBD (EAPC = -0.60%, 95% CI: -0.72 to - 0.48), MS (EAPC = -0.19%, 95% CI: -0.24 to -0.13) and psoriasis (EAPC = -0.77%, 95% CI: -0.78 to -0.76). From 2020 to 2040, the global ASIR of RA, IBD, and psoriasis was predicted to decrease whereas the global ASIR of MS was predicted to increase, with continuous increasing case number of all these diseases. Furthermore, the predicted incidence trends of these four ADs varied significantly across 195 countries and territories, with a prominent higher burden in high-income North America and Western Europe. CONCLUSIONS: There are strong heterogeneities in the global incidence trends (1990-2019) and predicted changes (2020-2040) of ADs across the world, highlighting prominent challenges in the control of ADs, including both growing case number and distributive disparities of these diseases worldwide, which may be instructive for better public health policy establishment and healthcare resource allocation.

Predictive validation of existing bleeding and thromboembolic scores in elderly patients with comorbid atrial fibrillation and acute coronary syndrome.

BACKGROUND: The validation of various risk scores in elderly patients with comorbid atrial fibrillation (AF) and acute coronary syndrome (ACS) has not been reported. The present study compared the predictive performance of existing risk scores in these patients. METHODS: A total of 1252 elderly patients with AF and ACS comorbidities (≥ 65 years old) were consecutively enrolled from January 2015 to December 2019. All patients were followed up for one year. The predictive performance of risk scores in predicting bleeding and thromboembolic events was calculated and compared. RESULTS: During the 1-year follow-up, 183 (14.6%) patients had thromboembolic events, 198 (15.8%) patients had BARC class ≥ 2 bleeding events, and 61 (4.9%) patients had BARC class ≥ 3 bleeding events. For the BARC class ≥ 3 bleeding events, discrimination of the existing risk scores was low to moderate, PRECISE-DAPT (C-statistic: 0.638, 95% CI: 0.611-0.665), ATRIA (C-statistic: 0.615, 95% CI: 0.587-0.642), PARIS-MB (C-statistic: 0.612, 95% CI: 0.584-0.639), HAS-BLED (C-statistic: 0.597, 95% CI: 0.569-0.624) and CRUSADE (C-statistic: 0.595, 95% CI: 0.567-0.622). However, the calibration was good. PRECISE-DAPT showed a higher integrated discrimination improvement (IDI) than PARIS-MB, HAS-BLED, ATRIA, and CRUSADE (P < 0.05) and the best decision curve analysis (DCA). For thromboembolic events, the discrimination of GRACE (C-statistic: 0.636, 95% CI: 0.608-0.662) was higher than CHA2DS2-VASc (C-statistic: 0.612, 95% CI: 0.584-0.639), OPT-CAD (C-statistic: 0.602, 95% CI: 0.574-0.629) and PARIS-CTE (C-statistic: 0.595, 95% CI: 0.567-0.622). The calibration was good. Compared to OPT-CAD and PARIS-CTE, the IDI of the GRACE score slightly improved (P < 0.05). However, NRI analysis showed no significant difference. DCA showed that the clinical practicability of thromboembolic risk scores was similar. CONCLUSIONS: The discrimination and calibration of existing risk scores in predicting 1-year thromboembolic and bleeding events were unsatisfactory in elderly patients with comorbid AF and ACS. PRECISE-DAPT showed higher IDI and DCA than other risk scores in predicting BARC class ≥ 3 bleeding events. The GRACE score showed a slight advantage in predicting thrombotic events.

Prediction of Diabetic Macular Edema Using Knowledge Graph.

Diabetic macular edema (DME) is a significant complication of diabetes that impacts the eye and is a primary contributor to vision loss in individuals with diabetes. Early control of the related risk factors is crucial to reduce the incidence of DME. Artificial intelligence (AI) clinical decision-making tools can construct disease prediction models to aid in the clinical screening of the high-risk population for early disease intervention. However, conventional machine learning and data mining techniques have limitations in predicting diseases when dealing with missing feature values. To solve this problem, a knowledge graph displays the connection relationships of multi-source and multi-domain data in the form of a semantic network to enable cross-domain modeling and queries. This approach can facilitate the personalized prediction of diseases using any number of known feature data. In this study, we proposed an improved correlation enhancement algorithm based on knowledge graph reasoning to comprehensively evaluate the factors that influence DME to achieve disease prediction. We constructed a knowledge graph based on Neo4j by preprocessing the collected clinical data and analyzing the statistical rules. Based on reasoning using the statistical rules of the knowledge graph, we used the correlation enhancement coefficient and generalized closeness degree method to enhance the model. Meanwhile, we analyzed and verified these models' results using link prediction evaluation indicators. The disease prediction model proposed in this study achieved a precision rate of 86.21%, which is more accurate and efficient in predicting DME. Furthermore, the clinical decision support system developed using this model can facilitate personalized disease risk prediction, making it convenient for the clinical screening of a high-risk population and early disease intervention.

Effectiveness of the recurrent laryngeal nerve monitoring during endoscopic thyroid surgery: systematic review and meta-analysis.

BACKGROUND: Thyroid disease is a common endocrine disorder, and thyroid surgeries and postoperative complications have increased recently. This study aimed to explore the effectiveness of intraoperative nerve monitoring (IONM) in endoscopic thyroid surgery using subgroup analysis and determine confounding factors. MATERIALS AND METHODS: Two researchers individually searched for relevant studies published till November 2022 in the PubMed, Embase, Web of Science and Cochrane Library databases. Eventually, eight studies met the inclusion criteria. Heterogeneity was assessed using the Cochran's Q test, and a funnel plot was implemented to evaluate publication bias. The odds ratio or risk difference were calculated using fixed-effects models. The weighted mean difference of continuous variables was calculated. Subgroup analysis was performed according to the disease type. RESULTS: Eight eligible papers included 915 patients and 1242 exposed nerves. The frequencies of transient, permanent and total recurrent laryngeal nerve (RLN) palsy were 2.64, 0.19 and 2.83%, respectively, in the IONM group and 6.15, 0.75 and 6.90%, respectively, in the conventional exposure group. In addition, analysis of the secondary outcome indicators for the average total length of surgery, localisation time of the RLN, recognition rate of the superior laryngeal nerve and length of incision revealed that IONM reduced the localisation time of the RLN and increased the identification rate of the superior laryngeal nerve. Subgroup analysis showed that IONM significantly reduced the incidence of RLN palsy in patients with malignancies. CONCLUSIONS: The use of IONM significantly reduced the incidence of transient RLN palsy during endoscopic thyroid surgery, but it did not significantly reduce the incidence of permanent RLN palsy. However, the reduction in the total RLN palsy was statistically significant. In addition, IONM can effectively reduce the location time of the RLN and increase the recognition rate of the superior laryngeal nerve. Therefore, the application of IONM for malignant tumours is recommended.

Pepsin Increases the Proliferation of Vocal Cord Leukoplakia Epithelial Cells by Inducing Autophagy.

OBJECTIVE: To investigate the role of H+ /K+ ATPase in the proliferation of pepsin-induced vocal cord leukoplakia (VCL) cells. STUDY DESIGN: Translation research. SETTING: Affiliated Hospital of University. METHODS: Immunohistochemistry was used to detect pepsin, H+ /K+ ATPase (ATP4A and ATP4B subunits) in VCL cells with varying degrees of dysplasia. After primary cultures of VCL cells had been established, the effects of acidified pepsin on the proliferation, autophagy, and H+ /K+ -ATPase distribution of VCL cells were investigated. RESULTS: The levels of pepsin, ATP4A, and ATP4B were significantly higher in VCL tissue with moderate-to-severe dysplasia than in normal tissue (p < .05); these levels gradually increased according to dysplasia severity. The expression levels of ATP4A and ATP4B were significantly correlated with the amount of pepsin in VCL cells (p < .01). Acidified pepsin enhanced the levels of proliferation and autophagy in human VCL epithelial cells. The cloning- and autophagy-promoting effects of acidified pepsin on VCL cells were partially reversed by pantoprazole; these effects were completely blocked by the autophagy inhibitor chloroquine. Finally, acidified pepsin promoted the colocalization of H+ /K+ -ATPase and lysosomes in VCL cells; it also mediated lysosome acidification. CONCLUSION: Pepsin and H+ /K+ -ATPase may contribute to the progression of VCL. Specifically, acidified pepsin may regulate lysosome acidification by promoting lysosomal localization of H+ /K+ -ATPase.

Spectral computed tomography-guided radiotherapy of osteosarcoma utilizing BiOI nanosheets.

As an aggressive malignant bone tumor, osteosarcoma (OS) is usually found in children and adolescents. Computed tomography (CT) is an important tool for the clinical evaluation of osteosarcoma, but limits to low diagnostic specificity due to single parameters of traditional CT and modest signal-to-noise ratio of clinical iodinated contrast agents. As one kind of spectral CT, dual-energy CT (DECT), with the advantage of a provision of multi-parameter information, makes it possible to acquire the best signal-to-noise ratio image, accurate detection, as well as imaging-guided therapy of bone tumors. Hereby, we synthesized BiOI nanosheets (BiOI NSs) as a DECT contrast agent with superior imaging capability compared to iodine agents for clinical detection of OS. Meanwhile, the synthesized BiOI NSs with great biocompatibility is able to achieve effective radiotherapy (RT) by enhancing X-ray dose deposition at the tumor site, leading to DNA damage, which in turn inhibits tumor growth. This study offers a promising new avenue for DECT imaging-guided treatment of OS. STATEMENT OF SIGNIFICANCE: Osteosarcoma (OS) is a common primary malignant bone tumor. Traditional surgical procedures and conventional CT scans are often used for the treatment and monitoring of OS, but the effects are generally unsatisfactory. In this work, BiOI nanosheets (NSs) was reported for dual-energy CT (DECT) imaging-guided OS radiotherapy. The powerful and constant X-ray absorption of BiOI NSs at any energy guarantees excellent enhanced DECT imaging performance, allowing detailed visualization of OS through images with a better signal-to-noise ratio and guiding radiotherapy process. The deposition of X-rays could be greatly enhanced by Bi atoms to induce serious DNA damage in radiotherapy. Taken together, the BiOI NSs for DECT-guided radiotherapy will greatly improve the current treatment status of OS.

Multiple Thyroglossal Duct Cysts: Clinical Experience and Literature Review.

Thyroglossal duct cysts (TDCs) are generally single cyst, multiple TDCs are rare. We describe a case of multiple TDCs, discuss its characteristic features and management, and provide a review of the literature, to improve clinical diagnosis and treatment. We report an extremely rare case of multiple TDCs containing five cysts, together with a review of the relevant English medical literature. To the best of our knowledge, this is the first reported case of TDCs containing more than three cysts in the anterior cervical region. The five cysts were completely excised in a Sistrunk operation. Histological examination of the cystic lesions revealed TDCs. The patient recovered well and no recurrence was found during the 6-year of follow-up. Multiple TDCs are extremely rare, and may be misdiagnosed as a single cyst. Clinicians should be aware of the possibility of multiple thyroglossal duct cysts. Adequate preoperative radiological examinations should be performed, and careful interpretation of the CT or MRI scans is important to diagnosis and surgery.

Interfering biosynthesis by nanoscale metal-organic frameworks for enhanced radiation therapy.

Radiation therapy (RT) is one of the most widely used cancer treatments. However, the vigorous biosynthesis of cancer cells plays an important role for RT resistance. Herein, we develop a hafnium-based nanoscale metal-organic frameworks (Hf-nMOFs) loaded with 3-bromopyruvate (3-BrPA) to overcome RT resistance and achieve favorable RT efficacy. The deposition of X-rays is greatly enhanced by Hf-nMOFs to induce stronger damage to DNA in RT. Simultaneously, as an inhibitor of glycolysis, the loaded 3-BrPA can reduce the supply of energy and interfere with the biosynthesis of proteins to decrease the DNA damage repair. As a result, the 3-BrPA@Hf-nMOFs (BHT) will overcome the RT resistance and enhance the curative effect of RT. Up and down-regulated genes as well as the related pathways in cellular metabolism and biosynthesis are well investigated to reveal the radiosensitization mechanism of BHT. In addition, the Hf element endows BHT with CT imaging capability to real-timely monitor the therapeutic process. Hence, the designed strategy of biosynthesis-targeted radiosensitization could decrease the doses of ionizing radiations and provide fresh perspectives on cancer treatment.

Paracoccus marinaquae sp. nov., isolated from coastal water of the Yellow Sea.

A Gram-stain-negative, non-motile and coccoid bacterial strain, designated XHP0099T, was isolated from the coastal water of the Yellow Sea, China. Growth occurred at 20-37 â„ƒ (optimum, 28 â„ƒ), pH 5.0-9.0 (optimum, pH 7.0-8.0), and with 0-7.0% NaCl (optimum, 2.0-3.0%). Phylogenetic analysis based on 16S rRNA gene sequences showed that strain XHP0099T was related to members of the genus Paracoccus and shared the highest sequence similarity with "P. siganidrum" M26 (98.2%), followed by P. alkanivorans 4-2 T (97.6%) and P. alkenifer DSM 11593 T (97.4%). The average nucleotide identity, amino acid identity, and digital DNA-DNA hybridization values of strain XHP0099T against related members in the genus Paracoccus were below the cut-off points proposed for the delineation of a novel species. The major cellular fatty acids (> 10%) were summed feature 8 (C18:1 ω7c/C18:1 ω6c), and C18:0. The major isoprenoid quinone was Q-10 and the polar lipids contained diphosphatidylglycerol (DPG), phosphatidylglycerol (PG), phosphatidylethanolamine (PE), phosphatidylcholine (PC), aminolipid (AL) and unidentified polar lipids (L). The G + C content of the genomic DNA of strain XHP0099T was 66.0%. Genomic analysis suggested that strain XHP0099T harbored gene clusters for formaldehyde and the XoxF-type methanol oxidation and type 1 Calvin cycle, which could confer the methylotrophy pathway. Based on the phenotypic, phylogenetic, biochemical and chemotaxonomic analysis, strain XHP0099T represents a novel species of the genus Paracoccus, for which the name Paracoccus marinaquae sp. nov. is proposed. The type strain is XHP0099T (= JCM 34661 T = GDMCC 1.2414 T = MCCC 1K05846T).

Real-Time In Situ Volatile Organic Compound Sensing by a Dual-Emissive Polynuclear Ln-MOF with Pronounced LnIII Luminescence Response.

Lanthanide metal-organic frameworks (Ln-MOFs) are promising for luminescence detection of volatile organic compound (VOC) vapors, but usually suffer from the silent or quenched Ln3+ emission. Herein, we report a new dual-emissive Eu-MOF composed of the coordinatively unsaturated Eu9 clusters that afford abundant open metal sites to form a confined "binding pocket" to facilitate the preconcentration and recognition of VOCs. Single-crystal structural analyses reveal that specific analytes can replace the OH oscillators in the first coordination sphere of Eu3+ and form a unique hydrogen-bonding second-sphere adduct tying adjacent Eu9 clusters together to minimize their nonradiative vibrational decay. With the promoted Eu3+ luminescence, the MOF realizes real-time in situ visual sensing of THF vapor (<1 s) and shows a quantitative ratiometric response to the vapor pressure with a limit of detection down to 17.33 Pa. Also, it represents a top-performing ratiometric luminescent thermometer.