Novel Intercellular Spread Mode of Respiratory Syncytial Virus Contributes to Neutralization Escape.

Developing widely used respiratory syncytial virus (RSV) vaccines remains a significant challenge, despite the recent authorization of two pre-F vaccines for elderly adults. Previous reports have suggested that even when vaccine-induced immunity generates high titers of potent neutralizing antibodies targeting the pre-F protein, it may not fully inhibit breakthrough of RSV infections. This incomplete inhibition of RSV breakthrough infections can lead to an increased risk of enhanced respiratory disease (ERD) in vaccinated individuals. The reasons why potent neutralizing antibodies cannot fully prevent RSV breakthrough infections are not yet clear. In an attempt to explain this phenomenon, we investigated the effect of potent neutralizing antibodies on the intercellular spread of RSV. Our findings indicated that a specific titer of potent neutralizing antibodies, such as 5C4, could block certain modes of intercellular spread, such as the diffusion of cell-free virions and the delivery of virions through filopodia. However, these antibodies did not fully inhibit the entire process of intercellular spread. Through the use of super-resolution imaging techniques, we observed a novel and efficient spread mode called the transition of viral materials through intercellular nanotubes (TVMIN), independent of virions and insensitive to the presence of antibodies. TVMIN allowed RSV-infected cells to directly transfer viral materials to neighboring cells via intercellular nanotubes that are rich in microfilaments. TVMIN began as early as 5 hours post-infection (h.p.i.) and rapidly initiated infection in recipient cells. Our data provided new insights into the intercellular spread of RSV and might help explain the occurrence of breakthrough infections.

Gypenoside XLIX alleviates sepsis-associated encephalopathy by targeting PPAR-α.

Sepsis-related systemic inflammation is a deadly condition with high rates of morbidity and mortality. There is evidence that sepsis affects the brain, and the most frequent organ dysfunction linked to sepsis is sepsis-associated encephalopathy. Sepsis-related brain damage can drastically reduce a patient's chances of survival. However, a specific treatment for sepsis-associated encephalopathy is not currently available. Consequently, to treat the brain damage caused by sepsis, investigating novel therapeutic strategies is imperative. After establishing the CLP-induced mouse SAE model, we treated the mice with Gyp-XLIX and evaluated apoptosis, neuroinflammation, brain damage, and oxidative stress in the brain tissue of each group of mice. Furthermore, the protective effects of Gyp-XLIX on LPS-treated BV-2 cells were assessed. We discovered that Gyp-XLIX treatment increased the survival rate of CLP-treated mice, alleviated SAE-related cerebral nerve abnormalities, and decreased blood-brain barrier breakdown, all of which could better preserve brain tissue in vivo. Furthermore, we identified associated proteins and found that Gyp-XLIX may reduce oxidative stress, cell apoptosis, and inflammation in the brain tissues of SAE mice. This observation was further validated in vitro. We established that Gyp-XLIX alleviates SAE by targeting PPAR-α. These findings may be important for the clinical applicability of Gyp-XLIX in SAE treatment. We found that Gyp-XLIX can alleviate brain injury in SAE by targeting PPAR-α and is a potential protective agent for SAE.

Comparative analysis of the therapeutic efficacy of remimazolam tosylate and propofol in older adults undergoing painless endoscopic retrograde cholangiopancreatography.

Objective: The aim of this study is to conduct a comparative analysis of the therapeutic outcomes associated with the administration of remimazolam and propofol during painless endoscopic retrograde cholangiopancreatography (ERCP) procedures in older adults. Methods: A total of 140 older adults who underwent elective painless ERCP were randomly assigned to two groups using the random number table method: the remimazolam group and the propofol group, each consisting of 70 patients. In the remimazolam group, anesthesia was administered using a combination of remimazolam and opioids, while in the propofol group, a combination of propofol and opioids was used. Comparative assessments between the two groups included anesthesia induction time, first induction success rate, intraoperative hemodynamics, awakening duration, stress response index, and the incidence of adverse reactions. Results: The remimazolam group exhibited a prolonged anesthesia induction time compared to the propofol group and a lower success rate of first induction (P < 0.05). At the point of endoscope entry (T2) and 10 min post-operation (T3), patients in the remimazolam group demonstrated higher mean arterial pressure (MAP), heart rate (HR), and bispectral index (BIS) values compared to those in the propofol group (P < 0.05). Furthermore, the remimazolam group had shorter durations for eye-opening, consciousness recovery, and residence in the recovery room compared to the propofol group (P < 0.05). Post-surgery levels of epinephrine (E), norepinephrine (NE), and cortisol (Cor) at 24 h were lower in the remimazolam group than in the propofol group (P < 0.05). The incidence of adverse reactions was significantly lower in the remimazolam group (18.57%) compared to the propofol group (31.43%) (P < 0.05). Conclusion: Remimazolam exhibits a longer induction time compared to propofol in the painless diagnosis and treatment of ERCP in older adults. However, it provides a more stable circulatory state post-induction and throughout the operation, reduces stress response, enables rapid recovery, and has a lower incidence of serious adverse reactions. These attributes suggest that remimazolam has potential for widespread clinical application and adoption. Clinical Trial Registration: clinicaltrials.gov, identifier ChiCTR2400080926.

Advances in the transport of oral nanoparticles in gastrointestinal tract.

Biological barriers in the gastrointestinal tract (GIT) prevent oral absorption of insoluble drugs. Recently, significant progress has been made in the development of various nanoparticles (NPs) designed to enhance the efficacy of oral drugs. However, the mechanism underlying the intracellular transport of NPs remains unclear, and there are still limitations to improving the oral bioavailability of drugs. This article reviews the challenges faced in the absorption of oral NPs, proposes strategies to overcome these barriers, and discusses the future prospects.

Application of Drug Delivery System Based on Nanozyme Cascade Technology in Chronic Wound.

Chronic wounds are characterized by long-term inflammation, including diabetic ulcers, traumatic ulcers, etc., which provide an optimal environment for bacterial proliferation. At present, antibiotics are the main clinical treatment method for chronic wound infections. However, the overuse of antibiotics may accelerate the emergence of drug-resistant bacteria, which poses a significant threat to human health. Therefore, there is an urgent need to develop new therapeutic strategies for bacterial infections. Nanozyme-based antimicrobial therapy (NABT) is an emerging antimicrobial strategy with broad-spectrum activity and low drug resistance compared to traditional antibiotics. NABT has shown great potential as an emerging antimicrobial strategy by catalyzing the generation of reactive oxygen species (ROS) with its enzyme-like catalytic properties, producing a powerful bactericidal effect without developing drug resistance. Nanozyme-based cascade antimicrobial technology offers a new approach to infection control, effectively improving antimicrobial efficacy by activating cascades against bacterial cell membranes and intracellular DNA while minimizing potential side effects. However, it is worth noting that this technology is still in the early stages of research. This article comprehensively reviews wound classification, current methods for the treatment of wound infection, different types of nanozymes, the application of nanozyme cascade reaction technology in antimicrobial therapy, and future challenges and prospects.

Characterization of Phytoplankton-Derived Amino Acids and Tracing the Source of Organic Carbon Using Stable Isotopes in the Amundsen Sea.

We utilized amino acid (AA) and carbon stable isotope analyses to characterize phytoplankton-derived organic matter (OM) and trace the sources of organic carbon in the Amundsen Sea. Carbon isotope ratios of particulate organic carbon (δ13C-POC) range from -28.7‱ to -23.1‱, indicating that particulate organic matter originated primarily from phytoplankton. The dissolved organic carbon isotope (δ13C-DOC) signature (-27.1 to -21.0‱) observed in the sea-ice melting system suggests that meltwater contributes to the DOC supply of the Amundsen Sea together with OM produced by phytoplankton. A negative correlation between the degradation index and δ13C-POC indicates that the quality of OM significantly influences isotopic fractionation (r2 = 0.59, p < 0.001). The AA distribution in the Amundsen Sea (5.43 ± 3.19 µM) was significantly larger than previously reported in the Southern Ocean and was associated with phytoplankton biomass (r2 = 0.49, p < 0.01). Under conditions dominated by P. antarctica (DI = 2.29 ± 2.30), OM exhibited greater lability compared to conditions co-dominated by diatoms and D. speculum (DI = 0.04 ± 3.64). These results highlight the important role of P. antarctica in influencing the properties of OM, suggesting potential impacts on carbon cycling and microbial metabolic activity in the Amundsen Sea.

The yeast Dothiora sorbi IOJ-3 naturally produced various filamentous sectors with distinct abilities by undergoing DNA demethylation.

Some fungi have demonstrated the ability to adapt rapidly to changing environments by exhibiting morphological plasticity, a trait influenced by species and environmental factors. Here, an anamorphic yeast strain IOJ-3 exhibited unique sectorization characteristics, naturally producing diverse filamentous sectors when cultivated on potato dextrose agar (PDA) medium or natural culture medium for durations exceeding 13 days. The strain IOJ-3 and its filamentous sectors were identified as Dothiora sorbi. The morphology of the sectors was consistent and heritable. The life cycle of strain IOJ-3 was investigated through microscopic observation, emphasizing the development of conidiogenous cells as a crucial stage, from which filamentous sectors originate. Some physiological characteristics of IOJ-3 and filamentous sectors are compared, and strain IOJ-3 has a higher antibiotic tolerance than two filamentous sectors, IOJ-3a expands faster on the culture medium, and IOJ-3b can penetrate cellophane. A transcriptomic analysis was conducted to investigate the differentially expressed genes between the yeast form IOJ-3 and its two filamentous sectors, revealing a total of 594 genes that exhibited consistent differential expression relative to IOJ-3, including 44 silencing genes in IOJ-3 that were activated. Gene Ontology analysis indicated that these differentially expressed genes were primarily associated with the cellular component category. Furthermore, adding 5-Azacytidine accelerated filamentous sectorization and increased the proportion of filamentous cells of strain IOJ-3 in PD liquid media, suggesting that the filamentous sectorization observed in strain IOJ-3 is linked to processes of DNA demethylation. In conclusion, this study sheds light on the biological characteristics of D. sorbi regarding morphological transitions and provides substantial direction for exploring genes related to fungal filamentous development.

Short-term outcomes and quality of life of esophagogastrostomy versus the double-tract reconstruction after laparoscopic proximal gastrectomy.

BACKGROUND: There is no optimal reconstruction technique after proximal gastrectomy. The esophagogastrostomy (EG) is a rather simple procedure technically, but the incidences of reflux esophagitis and anastomotic stricture are higher. While the double-tract reconstruction (DTR) can lessen postoperative reflux esophagitis, it is technically complex with a long operation time. The purpose of this study was to evaluate the quality of life (QoL) and short-term outcomes of the two reconstruction techniques. METHODS: We retrospectively collected consecutive patients with upper-third gastric adenocarcinoma and adenocarcinoma of the esophagogastric junction (AEG) at our center between 2019 June and 2023 May. Patients who underwent laparoscopic proximal gastrectomy (LPG) with EG or DTR were included in this study. A comparison was made between the clinical and pathological characteristics of patients and their surgical parameters, postoperative complications, and its 1-year QoL in two groups. The QoL of the two groups was assessed by Visick grading, the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and EORTC QLQ-STO22 scales at 1 year after operation. The nutritional status of the two groups was evaluated by BMI, hemoglobin and serum albumin. RESULTS: AII the qualified patients were divided EG group (n = 63) and DTR group (n = 93). Compared to the DTR group, the blood loss volume of EG group was more (p = 0.001). There were no significant differences in operation duration, number of lymph nodes dissected, and postoperative length of stay between the two groups(p > 0.05). No statistical differences were observed in terms of the incidence of early complications and Clavien-Dindo classification as well(p > 0.05). After one year, the Visick grade of the DTR group was better than EG group (p = 0.040). The multivariable logistic regression analysis showed the only independent risk factor for reflux esophagitis was the reconstruction method. According to the EORTC QLQ-C30 questionnaire, patients in the DTR group had a better global health status(p = 0.001) and complained less about nausea and vomiting(p = 0.033), and appetite loss (p = 0.022). Patients in the DTR group complained less about reflux (p = 0.030) based on the EORTC QLQ-STO22 questionnaire. The multiple linear regression analysis revealed that the reconstruction method, reflux esophagitis and age had a linear relationship with the global health status score. Regarding nutritional status, BMI of the two groups both decreased 1 year after operation, and BMI decline value of the DTR group was lower than EG group (p = 0.001). There is no statistically significant difference between the two groups as for postoperative change in hemoglobin and serum albumin. CONCLUSION: Our findings suggest that it is possible for skilled surgeons to achieve minimal blood loss volume without significantly increasing operation duration when performing DRT, which does not raise risk. In terms of anti-reflux, postoperative QoL and BMI maintenance, 1-year postoperative follow-up outcomes reveal the DTR is superior to EG, which deserve further research and promotion.

Mitochondria-Targetable Cyclometalated Iridium(III) Complex-Based Luminescence Probe for Monitoring and Assessing Treatment Response of Ferroptosis-Mediated Hepatic Ischemia-Reperfusion Injury.

Ferroptosis plays an essential role in the pathological progression of hepatic ischemia-reperfusion injury (HIRI), which is closely related to iron-dependent lipid peroxidation. Since mitochondria are thought to be the major site of reactive oxygen species (ROS) production and iron storage, monitoring the variations of mitochondrial hypochlorous acid (HClO) (an important member of ROS) has important implications for the assessment of ferroptosis status, as well as the formulation of treatment strategies for HIRI. However, reliable imaging tools for the visualization of mitochondrial HClO and monitoring its dynamic changes in ferroptosis-mediated HIRI are still lacking. Herein, in this work, an HClO-activated near-infrared (NIR) cyclometalated iridium(III) complex-based probe, named NIR-Ir-HClO, was developed for the visual monitoring of the mitochondrial HClO fluxes in ferroptosis-mediated HIRI. The newly prepared probe showed fast response (<30 s), good sensitivity, excellent selectivity, good cell biocompatibility, and satisfactory mitochondrial-targeting performance, making it suitable for accurate monitoring of mitochondrial HClO in living cells. Moreover, visualization of the variations of mitochondrial HClO in ferroptosis-mediated HIRI and monitoring of the treatment response of ferroptosis-mediated HIRI to the ferroptosis inhibitors were achieved for the first time. All these show that probe NIR-Ir-HClO can be utilized as a reliable imaging tool for revealing the pathological mechanism of mitochondrial HClO in ferroptosis-mediated HIRI, as well as for the formulation of new treatment strategies for HIRI.

Rice Protein Peptides Alleviate Alcoholic Liver Disease via the PPARγ Signaling Pathway: Through Liver Metabolomics and Gut Microbiota Analysis.

Alcoholic liver disease (ALD) is the predominant type of liver disease worldwide, resulting in significant mortality and a high disease burden. ALD damages multiple organs, including the liver, gut, and brain, causing inflammation, oxidative stress, and fat deposition. In this study, we investigated the effects of rice protein peptides (RPP) on ALD in mice with a primary focus on the gut microbiota and liver metabolites. The results showed that administration of RPP significantly alleviated the symptoms of ALD in mice including adiposity, oxidative stress, and inflammation. The KEGG pathway shows that RPP downregulates the liver metabolite of capric acid and the metabolism of fatty acid biosynthesis compared with the MOD group. Mechanistically, RPP downregulated the PPARγ signaling pathway and suppressed the expression of fatty acid biosynthesis genes (FASN, ACC1, ACSL1, and ACSL3). Furthermore, two active peptides (YLPTKQ and PKLPR) with potential therapeutic functions for ALD were screened by Caco-2 cell modeling and molecular docking techniques. In addition, RPP treatment alleviates gut microbiota dysbiosis by reversing the F/B ratio, increasing the relative abundance of Alloprevotella and Alistipes, and upregulating the level of short-chain fatty acids. In conclusion, RPP alleviates ALD steatosis through the PPARγ signaling pathway by YLPTKQ and PKLPR and regulates gut microbiota.

Recombinant Lactococcus lactis secreting FliC protein nanobodies for resistance against Salmonella enteritidis invasion in the intestinal tract.

Salmonella Enteritidis is a major foodborne pathogen throughout the world and the increase in antibiotic resistance of Salmonella poses a significant threat to public safety. Natural nanobodies exhibit high affinity, thermal stability, ease of production, and notably higher diversity, making them widely applicable for the treatment of viral and bacterial infections. Recombinant expression using Lactococcus lactis leverages both acid resistance and mucosal colonization properties of these bacteria, allowing the effective expression of exogenous proteins for therapeutic effects. In this study, nine specific nanobodies against the flagellar protein FliC were identified and expressed. In vitro experiments demonstrated that FliC-Nb-76 effectively inhibited the motility of S. Enteritidis and inhibited its adhesion to and invasion of HIEC-6, RAW264.7, and chicken intestinal epithelial cells. Additionally, a recombinant L. lactis strain secreting the nanobody, L. lactis-Nb76, was obtained. Animal experiments confirmed that it could significantly reduce the mortality rates of chickens infected with S. Enteritidis, together with alleviating the inflammatory response caused by the pathogen. These results provide a novel strategy for the treatment of antibiotic-resistant S. Enteritidis infection in the intestinal tract.

Targeting VPS18 hampers retromer trafficking of PD-L1 and augments immunotherapy.

Immune checkpoint inhibitors targeting programmed cell death 1 (PD-1) or programmed cell death-ligand 1 (PD-L1) have achieved impressive antitumor clinical outcomes. However, the limited response rates suggest the incomplete understanding of PD-L1 regulation. Here, we demonstrate that vacuole protein sorting 11 and 18 (VPS11/18), two key players in vesicular trafficking, positively regulate PD-L1 and confer resistance to immune checkpoint blockade therapy. VPS11/18 interact with PD-L1 in endosome recycling accompanied by promoting PD-L1 glycosylation and protein stability. VPS18 deficiency enhances antitumor immune response. Pharmacological inhibition by VPS18 inhibitor RDN impaired PD-L1 member trafficking and protein stability. Combination treatment of RDN and anti-cytotoxic T lymphocyte-associated antigen 4 synergistically enhances antitumor efficacy in aggressive and drug-resistant tumors. RDN exerted lung-preferred distribution and good bioavailability, suggesting a favorable drug efficacy. Together, our study links VPS18/11-mediated trans-Golgi network recycling of PD-L1 and points to a promising treatment strategy for the enhancement of antitumor immunity.

The shift current photovoltaic effect response in wurtzite and zinc blende semiconductors via first-principles calculations.

Recently, the search for materials with high photoelectric conversion efficiency has emerged as a significant research hotspot. Unlike p-n junctions, the bulk photovoltaic effect (BPVE) can also materialize within pure crystals. Here, we propose wurtzite and zinc blende semiconductors without inversion symmetry (AgI, GaAs, CdSe, CdTe, SiGe, ZnSe, and ZnTe) as candidates for achieving the BPVE and investigate the factors that affect the shift current. GaAs with a wurtzite structure exhibits the highest shift current value of 31.8 µA V-2 when spin-orbit coupling is considered. Meanwhile, the peak position of the maximum linear optical conductivity and shift current in the wurtzite structure is lower than that in the zinc blende structure. In addition, we also found that strong covalency within the same main axis group element significantly influences the shift current, exemplified by wurtzite SiGe, which exhibits 15.8 µA V-2. Our research highlights the importance of a smaller band gap, reduced carrier effective mass, and increased covalency in achieving a substantial shift current response. Ultimately, this study provides valuable insights into the interplay of the structural and electronic properties, offering directions for the discovery and design of materials with an enhanced BPVE.

Seasonal variations of microbial communities and viral diversity in fishery-enhanced marine ranching sediments: insights into metabolic potentials and ecological interactions.

BACKGROUND: The ecosystems of marine ranching have enhanced marine biodiversity and ecological balance and have promoted the natural recovery and enhancement of fishery resources. The microbial communities of these ecosystems, including bacteria, fungi, protists, and viruses, are the drivers of biogeochemical cycles. Although seasonal changes in microbial communities are critical for ecosystem functioning, the current understanding of microbial-driven metabolic properties and their viral communities in marine sediments remains limited. Here, we employed amplicon (16S and 18S) and metagenomic approaches aiming to reveal the seasonal patterns of microbial communities, bacterial-eukaryotic interactions, whole metabolic potential, and their coupling mechanisms with carbon (C), nitrogen (N), and sulfur (S) cycling in marine ranching sediments. Additionally, the characterization and diversity of viral communities in different seasons were explored in marine ranching sediments. RESULTS: The current study demonstrated that seasonal variations dramatically affected the diversity of microbial communities in marine ranching sediments and the bacterial-eukaryotic interkingdom co-occurrence networks. Metabolic reconstruction of the 113 medium to high-quality metagenome-assembled genomes (MAGs) was conducted, and a total of 8 MAGs involved in key metabolic genes and pathways (methane oxidation - denitrification - S oxidation), suggesting a possible coupling effect between the C, N, and S cycles. In total, 338 viral operational taxonomic units (vOTUs) were identified, all possessing specific ecological characteristics in different seasons and primarily belonging to Caudoviricetes, revealing their widespread distribution and variety in marine sediment ecosystems. In addition, predicted virus-host linkages showed that high host specificity was observed, with few viruses associated with specific hosts. CONCLUSIONS: This finding deepens our knowledge of element cycling and viral diversity in fisheries enrichment ecosystems, providing insights into microbial-virus interactions in marine sediments and their effects on biogeochemical cycling. These findings have potential applications in marine ranching management and ecological conservation. Video Abstract.

The clinical application of metagenomic next-generation sequencing in immunocompromised patients with severe respiratory infections in the ICU.

BACKGROUND: Early targeted antibiotic therapy is crucial for improving the prognosis of immunocompromised patients with severe respiratory infections (SRIs) in the intensive care unit (ICU). Metagenomic next-generation sequencing (mNGS) has shown significant value in pathogen detection, but research on lower respiratory tract microorganisms remains limited. METHODS: This study enrolled 234 patients with SRIs in the ICU, and individuals were categorized into immunocompromised and immunocompetent groups. We compared the diagnostic performance of mNGS using bronchoalveolar lavage fluid (BALF) with conventional microbiological tests (CMTs) and analyzed the value of mNGS in immunocompromised patients with SRIs in the ICU. RESULTS: Among all patients, the pathogenic microorganism detection rate of mNGS was higher than that of CMTs (94.02% vs 66.67%, P < 0.05), both in the immunocompromised group (95.0% vs 58.75%, P < 0.05) and the immunocompetent group (93.51% vs 71.43%, P < 0.05). mNGS detected more pathogens than CMTs did (167 vs 51), identifying 116 organisms that were missed by CMTs. The proportion of antibiotic regimen adjustments based on mNGS results was significantly higher compared to CMTs in both the immunocompromised (70.00% vs 17.50%, P < 0.05) and immunocompetent groups (48.70% vs 15.58%, P < 0.05). In the immunocompromised group, patients who had their antibiotic treatment adjusted on mNGS results had improved prognosis, with significantly lower ICU mortality (8.93% vs 50%, P < 0.05) and 28-day mortality rates (30.36% vs 68.75%, P < 0.05) than CMTs. In the immunocompetent group, no statistically significant differences were observed in ICU mortality or 28-day mortality (20.00% vs 33.33%, P > 0.05; 42.67% vs 45.83%, P > 0.05). CONCLUSION: mNGS shows significant value in detecting pathogens in immunocompromised patients with SRIs in ICU. For immunocompromised patients who respond poorly to empirical treatment, mNGS can provide an etiological basis, helping adjust antibiotic regimens more precisely and thereby improving patient prognosis.

Cardiac thrombus detected by cardiac computed tomography angiography in patients with acute ischemic stroke: a meta-analysis.

Background: Detecting cardiac thrombus in patients with acute ischemic stroke is crucial in determine stroke etiology and predict prognosis. However, the prevalence of cardiac thrombus in patients with acute ischemic stroke is unclear. Object: This study aimed to evaluate the prevalence of cardiac thrombus detected by cardiac computed tomography angiography (CCTA) in patients with acute ischemic stroke through a meta-analysis. Methods: Embase, Web of Science, MEDLINE, and CENTRAL were searched from January 1, 2000, to May 1, 2024. We included observational studies enrolling patients who underwent CCTA within 1 month following acute ischemic stroke, and reporting the incidence of cardiac thrombi on CCTA. Meta-analysis was performed using random effects models. Results: Twenty-six studies involving 4,516 patients were identified. The pooled prevalence of cardiac thrombus detected on CCTA in patients with acute ischemic stroke was 0.08 (95% confidence interval [CI]: 0.06-0.11). Inter-study heterogeneity was high (I2 = 88%). Among stroke type, the prevalence of atrial fibrillation, timing of CCTA and CCTA technology, the prevalence of atrial fibrillation was the only factor associated with cardiac thrombi prevalence detected by CCTA. However, atrial fibrillation was not documented in 41.5% of the patients with cardiac thrombi. Conclusion: CCTA is a useful non-invasive imaging approach for detecting cardiac thrombus in patients with acute ischemic stroke, which might be helpful to determine the stroke etiology.

The role of KRT7 in metastasis and prognosis of pancreatic cancer.

PURPOSE: The aim of this study is to delve into the value of N6-Methyladenosine (m6A)-associated genes (MAGs) in pancreatic cancer (PC) prognosis. METHODS: PC sequencing data and corresponding clinicopathological information were retrieved from GEO and TCGA databases. We filtered 19 MAGs in PC specimens and implemented functional annotation in biology. Later, the m6A modification pattern was stratified into m6Acluster A-B according to MAG expression levels, and further categorized into genecluster A-C based on differentially expressed genes between m6Acluster A and B. Next, a MAG-based prognostic prediction model was established by the least absolute shrinkage and selection operator (LASSO) regression analysis and multivariate Cox regression analysis. At last, the role of KRT7 in PC were explored. RESULTS: We found m6Acluster A pattern presented enrichment pathways associated with cell apoptosis, proliferation, migration, and cancer pathways. Additionally, high-risk group displayed more dismal prognosis and a higher programmed death-ligand 1 expression. The survival prediction ability of the model was verified in three independent PC GEO datasets. KRT7 is the most momentous risk gene in the established prognostic model. Among 18 clinical samples, the KRT7 protein in the surviving patient samples is lower than that in the deceased patient samples. We also identified elevated expression of KRT7 in PC tumor tissues compared to normal tissues using GEPIA 2. Then, the metastasis of PC cells was promoted by overexpressed KRT7 in vitro and in vivo. And IGF2BP3 upregulated KRT7 by increasing the mRNA stability of KRT7. CONCLUSIONS: The PPM built based on CXCL5, LY6K and KRT7 is an encouraging biomarker to define the prognosis. Additionally, IGF2BP3 promoted KRT7 by stabilizing mRNA of KRT7. And KRT7 promoted the metastasis of PC cells by promoting EMT.

Evaluation of a new scoring system for assessing nerve invasion in resected pancreatic cancer: A single-center retrospective analysis.

Nerve invasion (NI) is a characteristic feature of pancreatic cancer. Traditional dichotomous statements on the presence of NI are unreasonable because almost all cases exhibit NI when sufficient pathological sections are examined. The critical implications of NI in pancreatic cancer highlight the need for a more effective criterion. This study included 511 patients, who were categorized into a training group and a testing group at a ratio of 7:3. According to the traditional definition, NI was observed in 91.2 % of patients using five pathological slides in our study. The prevalence of NI increased as more pathological slides were used. The criterion of 'two points of intraneural (endoneural) invasion in the case of four pathological slides' has the highest receiver operating characteristic (ROC) score. Based on this new criterion, NI was proved to be an independent prognostic factor for overall survival (OS) and disease-free survival (DFS) and was also correlated with tumor recurrence (P = 0.004). Interestingly, gemcitabine-based chemotherapy regimen is an independent favorable factor for patients with high NI. In the high NI group, patients who received a gemcitabine-based regimen exhibited a better prognosis than those who did not receive the gemcitabine-based regimen for OS (P = 0.000) and DFS (P = 0.001). In conclusion, this study establishes assessment criteria to evaluate the severity of NI in order to predict patient outcomes.

Engineering Injectable Coassembled Hydrogel by Photothermal Driven Chitosan-Stabilized MoS2 Nanosheets for Infected Wound Healing.

The application of enzyme-like molybdenum disulfide (MoS2) in tissue repair was confronted with stable dispersion, solubilization, and biotoxicity. Here, the injectable self-healing hydrogel was successfully designed using a step-by-step coassembly of chitosan and MoS2. Polyphenolic chitosan as a "structural stabilizer" of MoS2 nanosheets reconstructed well-dispersed MoS2@CSH nanosheets, which improved the biocompatibility of traditional MoS2, and strengthened its photothermal conversion and enzyme-like activities, guaranteeing highly efficient radical scavenging and antimicrobial properties. Furthermore, the polyphenol chitosan was employed again as a "molecular cross-linking agent" to form the injectable NIR-responsive MoS2@CSH hydrogel by accelerating hydrogen-bond interaction among chitosan and the multicross-linking reaction among polyphenols. The rapid self-healing ability was conducive to wound closure and dynamic adaptability. An experimental study on infected wound healing demonstrated that MoS2@CSH hydrogel could substantially eradicate bacteria and accelerate the angiogenesis of infected wounds. The photothermal-driven coassembly of MoS2 and polycation provided an alternative strategy for infected wound healing.