Effect of desflurane anesthesia on flash visual evoked potential monitoring in patients undergoing spine surgery: study protocol for a randomized controlled trial.

BACKGROUND: Flash visual evoked potentials (FVEPs) are a reliable method for protecting visual function during spine surgery in prone position. However, the popularization and application of FVEPs remain limited due to the unclear influence of various anesthetics on FVEPs. Exploring the effects of anesthetic drugs on FVEP and establishing appropriate anesthesia maintenance methods are particularly important for promoting and applying FVEP. According to the conventional concept, inhaled narcotic drugs significantly affect the success of FVEP monitoring, FVEP extraction, and interpretation. Nonetheless, our previous study demonstrated that sevoflurane-propofol balanced anesthesia was a practicable regimen for FVEPs. Desflurane is widely used in general anesthesia for its rapid recovery properties. As the effect of desflurane on FVEP remains unclear, this trial will investigate the effect of different inhaled concentrations of desflurane anesthesia on amplitude of FVEPs during spine surgery, aiming to identify more feasible anesthesia schemes for the clinical application of FVEP. METHODS/ DESIGN: A total of 70 patients undergoing elective spinal surgery will be enrolled in this prospective, randomized controlled, open-label, patient-assessor-blinded, superiority trial and randomly assigned to the low inhaled concentration of desflurane group (LD group) maintained with desflurane-propofolremifentanil-balanced anesthesia or high inhaled concentration of desflurane group (HD group) maintained with desflurane-remifentanil anesthesia maintenance group at a ratio of 1:1. All patients will be monitored for intraoperative FVEPs, and the baseline will be measured half an hour after induction under total intravenous anesthesia (TIVA). After that, patients will receive 0.5 minimum alveolar concentration (MAC) of desflurane combined with propofol and remifentanil for anesthesia maintenance in the LD group, while 0.7-1.0 MAC of desflurane and remifentanil will be maintained in the HD group. The primary outcome is the N75-P100 amplitude 1 h after the induction of anesthesia. We intend to use the dual measure evaluation, dual data entry, and statistical analysis by double trained assessors to ensure the reliability and accuracy of the results. DISCUSSION: This randomized controlled trial aims to explore the superiority effect of low inhaled concentration of desflurane combined with propofolremifentanil-balanced anesthesia versus high inhaled concentration of desflurane combined with remifentanil anesthesia on amplitude of FVEPs. The study is meant to be published in a peer-reviewed journal and might guide the anesthetic regimen for FVEPs. The conclusion is expected to provide high-quality evidence for the effect of desflurane on FVEPs and aim to explore more feasible anesthesia schemes for the clinical application of FVEPs and visual function protection. TRIAL REGISTRATION: This study was registered on clinicaltrials.gov on July 15, 2022. CLINICALTRIALS: gov Identifier: NCT05465330.

The fluorescence mKate2 labeling as a visualizing system for monitoring small extracellular vesicles.

Small extracellular vesicles (sEVs) are nanosized vesicles enclosed in a lipid membrane released by nearly all cell types. sEVs have been considered as reliable biomarkers for diagnostics and effective carriers. Despite the clear importance of sEV functionality, sEV research faces challenges imposed by the small size and precise imaging of sEVs. Recent advances in live and high-resolution microscopy, combined with efficient labeling strategies, enable us to investigate the composition and behavior of EVs within living organisms. Here, a modified sEVs was generated with a near infrared fluorescence protein mKate2 using a VSVG viral pseudotyping-based approach for monitoring sEVs. An observed was made that the mKate2-tagged protein can be incorporated into the membranes of sEVs without altering their physical properties. In vivo imaging demonstrates that sEVs labeled with mKate2 exhibit excellent brightness and high photostability, allowing the acquisition of long-term investigation comparable to those achieved with mCherry labeling. Importantly, the mKate2-tagged sEVs show a low toxicity and exhibit a favorable safety profile. Furthermore, the co-expression of mKate2 and rabies virus glycoprotein (RVG) peptide on sEVs enables brain-targeted visualization, suggesting the mKate2 tag does not alter the biodistribution of sEVs. Together, the study presents the mKate2 tag as an efficient tracker for sEVs to monitor tissue-targeting and biodistribution in vivo.

Acidification Offset Warming-Induced Increase in N2O Production in Estuarine and Coastal Sediments.

Global warming and acidification, induced by a substantial increase in anthropogenic CO2 emissions, are expected to have profound impacts on biogeochemical cycles. However, underlying mechanisms of nitrous oxide (N2O) production in estuarine and coastal sediments remain rarely constrained under warming and acidification. Here, the responses of sediment N2O production pathways to warming and acidification were examined using a series of anoxic incubation experiments. Denitrification and N2O production were largely stimulated by the warming, while N2O production decreased under the acidification as well as the denitrification rate and electron transfer efficiency. Compared to warming alone, the combination of warming and acidification decreased N2O production by 26 ± 4%, which was mainly attributed to the decline of the N2O yield by fungal denitrification. Fungal denitrification was mainly responsible for N2O production under the warming condition, while bacterial denitrification predominated N2O production under the acidification condition. The reduced site preference of N2O under acidification reflects that the dominant pathways of N2O production were likely shifted from fungal to bacterial denitrification. In addition, acidification decreased the diversity and abundance of nirS-type denitrifiers, which were the keystone taxa mediating the low N2O production. Collectively, acidification can decrease sediment N2O yield through shifting the responsible production pathways, partly counteracting the warming-induced increase in N2O emissions, further reducing the positive climate warming feedback loop.

Red blood cell transfusion in neurocritical patients: a systematic review and meta-analysis.

BACKGROUND: Anemia can lead to secondary brain damage by reducing arterial oxygen content and brain oxygen supply. Patients with acute brain injury have impaired self-regulation. Brain hypoxia may also occur even in mild anemia. Red blood cell (RBC) transfusion is associated with increased postoperative complications, poor neurological recovery, and mortality in critically ill neurologic patients. Balancing the risks of anemia and red blood cell transfusion-associated adverse effects is challenging in neurocritical settings. METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), Embase, and MEDLINE (PubMed) from inception to January 31, 2024. We included all randomized controlled trials (RCTs) assessing liberal versus restrictive RBC transfusion strategies in neurocritical patients. We included all relevant studies published in English. The primary outcome was mortality at intensive care unit (ICU), discharge, and six months. RESULTS: Of 5195 records retrieved, 84 full-text articles were reviewed, and five eligible studies were included. There was no significant difference between the restrictive and liberal transfusion groups in ICU mortality (RR: 2.53, 95% CI: 0.53 to 12.13), in-hospital mortality (RR: 2.34, 95% CI: 0.50 to 11.00), mortality at six months (RR: 1.42, 95% CI: 0.42 to 4.78) and long-term mortality (RR: 1.22, 95% CI: 0.64 to 2.33). The occurrence of neurological adverse events and most major non-neurological complications was similar in the two groups. The incidence of deep venous thrombosis was lower in the restrictive strategy group (RR: 0.41, 95% CI: 0.18 to 0.91). CONCLUSIONS: Due to the small sample size of current studies, the evidence is insufficiently robust to confirm definitive conclusions for neurocritical patients. Therefore, further investigation is encouraged to define appropriate RBC transfusion thresholds in the neurocritical setting.

Construction of exosome-loaded LL-37 and its protection against zika virus infection.

Zika virus (ZIKV) is an enveloped, single-stranded and positive-stranded RNA virus of the genus Flavivirus in the family Flaviviridae. ZIKV can cross the placental barrier and infect the fetus, causing microcephaly, congenital ZIKV syndrome, and even fetal death. ZIKV infection can also lead to testicular damage and male sterility. But no effective drugs and vaccines are available up to now. Previous studies have shown that the cathelicidin antimicrobial peptide LL-37 can protect against ZIKV infection. However, LL-37 is a secreted peptide, which can be easily degraded in vivo. We herein constructed exosome-loaded LL-37 (named LL-37-TM-exo and TM-LL-37-exo) using the transmembrane protein TM to load LL-37 onto the membrane of exosome. We found that exosome-loaded LL-37 could significantly inhibit ZIKV infection in vitro and in vivo, and LL-37-TM-exo had stronger antiviral activity than that of TM-LL-37-exo, which could significantly reduce ZIKV-induced testicular injury and sperm injury, and had broad-spectrum antiviral effect. Compared to free LL-37, exosome-loaded LL-37 showed a better serum stability, higher efficiency to cross the placental barrier, and stronger antiviral activity. The mechanism of exosome-loaded LL-37 against ZIKV infection was consistent with that of free LL-37, which could directly inactivate viral particles, reduce the susceptibility of host cells, and act on viral replication stage. Our study provides a novel strategy for the development of LL-37 against viral infection.

Effect of esketamine combined with pregabalin on acute postsurgical pain in patients who underwent resection of spinal neoplasms: a randomized controlled trial.

ABSTRACT: Moderate-to-severe acute postsurgical pain (APSP) can prolong the recovery and worsen the prognosis of patients who undergo spinal surgery. Esketamine and pregabalin may resolve APSP without causing hyperpathia or respiratory depression after surgery. However, there are other risks, such as dissociative symptoms. We designed a randomized controlled trial to investigate the effect of the combination of these 2 drugs on the incidence of APSP in patients who underwent resection of spinal neoplasms. Patients aged 18 to 65 years were randomized to receive esketamine (a bolus dose of 0.5 mg·kg-1 and an infusion dose of 0.12 mg·kg-1·h-1 for 48 hours after surgery) combined with oral pregabalin (75-150 mg/day, starting 2 hours before surgery and ending at 2 weeks after surgery) or an identical volume of normal saline and placebo capsules. The primary outcome was the proportion of patients with moderate-to-severe APSP (visual analog scale score ≥ 40) during the first 48 hours after surgery. Secondary outcomes included the incidence of drug-related adverse events. A total of 90 patients were randomized. The incidence of moderate-to-severe APSP in the combined group (27.3%) was lower than that in the control group (60.5%) during the first 48 hours after surgery (odds ratio = 0.25, 95% CI = 0.10-0.61; P = 0.002). The occurrence of mild dissociative symptoms was higher in the combined group than in the control group (18.2% vs 0%). In conclusion, esketamine combined with pregabalin could effectively alleviate APSP after spinal surgery, but an analgesic strategy might increase the risk of mild dissociative symptoms.

Cyanuric Acid-Functionalized Perovskite Nanocrystals toward Low Interface Impedance, High Environmental Stability, and Superior Electrochemiluminescence.

Perovskite nanocrystals (PNs) have received much attention as luminescence materials in the field of electrochemiluminescence (ECL). However, as one key factor for determining the optoelectronic properties of the surface state of PNs, the surface passivation layer of PNs has enormous difficulty in simultaneously meeting the requirements of high ECL efficiency, conductivity, and stability. Herein, an effective surface modification strategy with cyanuric acid (CA) is used to solve such issue. As confirmed, the CA molecules are chemically anchored onto the surface of PNs via the Lewis interaction between π electrons of the triazine ring and the empty orbit of Pb2+. Benefiting from the above interaction, the electrochemical impedance of PNs is decreased greatly without the loss of light-emitting efficiency. Moreover, the stability of PNs under O2 exposure is improved by almost sixfold. These improvements are confirmed to be beneficial for enhancing the ECL behaviors of PNs under electrochemical operation. Upon cathode ECL driving conditions in aqueous media, the ECL intensity and efficiency of PNs are increased to 200 and 170%, respectively. This work provides a new modification strategy to holistically improve the ECL performance of PNs, which is instructive to exploring robust perovskite nanomaterials for electrochemical applications.

Keratinocyte derived HMGB1 aggravates psoriasis dermatitis via facilitating inflammatory polarization of macrophages and hyperproliferation of keratinocyte.

Psoriasis is one of the most common immune-mediated chronic inflammatory skin diseases, involving excessive proliferation of keratinocyte and infiltration of immune cells. There are many factors that cause the onset of psoriasis, so the exact pathogenesis of psoriasis still needs to be determined. High mobility group box-1 (HMGB1), a pro-inflammatory cytokine, is closely related to the pathogenesis of various inflammatory diseases. However, there are few studies investigating the effects of HMGB1 on inflammatory dermatoses. Here, we found that keratinocyte in the the IMQ-treated skin lesions of psoriasis model mice expressed more HMGB1. Notably, HMGB1 produced by keratinocyte could promote the activation of inflammatory type macrophages without affecting the polarization of anti-inflammatory type macrophages. Meanwhile, the proportion of M1 type macrophages in the skin lesions is significantly increased. Moreover, local clearance of macrophages in the skin could alleviate psoriasis like inflammation. Finally, keratinocyte-derived HMGB1 could also act on itself in turn, promoting the excessive proliferation and the mRNA expression of inflammatory cytokines of keratinocyte. Therefore, this study not only found the effect of HMGB1 on the hyperproliferation of keratinocyte, but also revealed that keratinocyte could communicate with macrophages through HMGB1, thereby facilitating macrophage inflammatory polarization. Collectively, these findings have clinical significance for the research and treatment of psoriasis, HMGB1 may become a potential target for the treatment of psoriasis.

Differential traits between microvesicles and exosomes in enterovirus infection.

Extracellular vesicles (EVs), including exosomes and microvesicles (MVs), are released by most cell types into the extracellular space and represent the pathophysiological condition of their source cells. Recent studies demonstrate that EVs derived from infected cells and tumors contribute to disease pathogenesis. However, very few studies have rigorously characterized exosomes and microvesicles in infectious diseases. In this study, we focused on subpopulations of EVs during the human enterovirus infection and explored the distinct traits and functions of EVs. We construct an effective immunomagnetic method to isolate exosomes and MVs from enterovirus-infected cells excluding virion. The morphology and sizes of exosomes and MVs have no significant alteration after enterovirus infection. Meanwhile, our study observed that the enterovirus infection could induce exosome secretion but not MVs. In vivo study showed that there was differential biodistribution between exosomes and MVs. Using deep RNA sequencing, we found that the cargo information in MVs rather than in exosomes could accurately reflect pathological condition of original cells. Our study demonstrated that it should be considered to use MVs as clinical diagnostics during in enterovirus infection because their composition is reflective of pathological changes.

Caffeic acid phenethyl ester suppresses metastasis of breast cancer cells by inactivating FGFR1 via MD2.

BACKGROUND: Tumor metastasis is the main cause of death for breast cancer patients. Caffeic acid phenethyl ester (CAPE) has strong anti-tumor effects with very low toxicity and may be a potential candidate drug. However, the anti-metastatic effect and molecular mechanism of CAPE on breast cancer need more research. METHODS: MCF-7 and MDA-MB-231 breast cancer cells were used here. Wound healing and Transwell assay were used for migration and invasion detection. Western blot and RT-qPCR were carried out for the epithelial-to-myofibroblast transformation (EMT) process investigation. Western blot and immunofluorescence were performed for fibroblast growth factor receptor1 (FGFR1) phosphorylation and nuclear transfer detection. Co-immunoprecipitation was used for the FGFR1/myeloid differentiation protein2 (MD2) complex investigation. RESULTS: Our results suggested that CAPE blocks the migration, invasion, and EMT process of breast cancer cells. Mechanistically, CAPE inhibits FGFR1 phosphorylation and nuclear transfer while overexpression of FGFR1 reduces the anti-metastasis effect of CAPE. Further, we found that FGFR1 is bound to MD2, and silencing MD2 inhibits FGFR1 phosphorylation and nuclear transfer as well as cell migration and invasion. CONCLUSION: This study illustrated that CAPE restrained FGFR1 activation and nuclear transfer through MD2/FGFR1 complex inhibition and showed good inhibitory effects on the metastasis of breast cancer cells.

Effects of Ketamine on Chronic Postsurgical Pain in Patients Undergoing Surgery: A Systematic Review and Meta-analysis.

BACKGROUND: Chronic postsurgical pain (CPSP) has become a common complication during the perioperative period. The efficacy of one of the most potent strategies, ketamine, remains unclear. OBJECTIVES: The aim of this meta-analysis was to evaluate the effect of ketamine on CPSP in patients undergoing common surgeries.. STUDY DESIGN: Systematic review and meta-analysis. METHODS: English-language randomized controlled trials (RCTs) published in MEDLINE, Cochrane Library, and EMBASE from 1990 through 2022 were screened. RCTs with a placebo control group that evaluated the effect of intravenous ketamine on CPSP in patients undergoing common surgeries were included. The primary outcome was the proportion of patients who experienced CPSP 3 - 6 months postsurgery. The secondary outcomes included adverse events, emotional evaluation, and 48 hour postoperative opioid consumption. We followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Pooled effect sizes were measured using the common-effects model or random-effects model, and several subgroup analyses were conducted. RESULTS: Twenty RCTs were included with 1,561 patients. Our pooled meta-analysis showed a significant difference between ketamine and placebo in the treatment of CPSP (Relative Risk [RR] = 0.86; 95% CI, 0.77 - 0.95; P = 0.02; I2 = 44%). In the subgroup analyses, our results indicated that compared with placebo, intravenous ketamine might decrease the prevalence of CPSP 3 - 6 months postsurgery (RR = 0.82; 95% CI, 0.72 - 0.94; P = 0.03; I2 = 45%). For adverse events, we observed that intravenous ketamine might lead to hallucinations (RR = 1.61; 95% CI, 1.09 - 2.39; P = 0.27; I2 = 20%) but did not increase the incidence of postoperative nausea and vomiting (RR = 0.98; 95% CI, 0.86 - 1.12; P = 0.66; I2 = 0%). LIMITATIONS: Inconsistent assessment tools and follow-up for chronic pain may contribute to the high heterogeneity and limitation of this analysis. CONCLUSIONS: We discovered that intravenous ketamine may reduce the incidence of CPSP in patients undergoing surgery, especially 3 - 6 months postsurgery. Because of the small sample size and high heterogeneity of the included studies, the effect of ketamine in the treatment of CPSP still needs to be explored in future large-sample, standardized-assessment studies.

Infection by exosome-carried Coxsackievirus B3 induces immune escape resulting in an aggravated pathogenesis.

Increasing evidence has shown that extracellular vesicles or exosomes released from virus-infected cells contain viral particles, genomes, or other pathogenic factors that move to neighbor cells, contributing to virus dissemination and productive infection. Our recent study demonstrated that exosomes carrying CVB3 virions exhibited greater infection efficiency than free virions because they accessed various entry routes, overcoming restrictions to viral tropism. However, the pathogenicity of exosomes carried CVB3 and their effect on immunological properties have not yet been completely explained. In the current study, we sought to explore whether exosomes exert their effect on the CVB3-induced pathogenesis or evade the immune attack. Our results showed that exosomes-carried CVB3 could effectively infect viral receptor-negative immune cells in vivo, resulting in inducing immune system loss. Importantly, the exosomes-carried CVB3 had the ability to escape the neutralizing antibodies activity resulting in inducing the severe onset of myocarditis. Using the genetically engineered mouse with deficiency of exosomes, we observed that the exosomes-carried CVB3 reinforced an aggravated pathogenesis. By understanding how exosomes promote the course of viral disease, clinical applications of exosomes can be developed.

Identification and validation of the microRNAs and hub genes for pancreatic ductal adenocarcinoma by an integrated bioinformatic analysis.

Background: In the progression of pancreatic ductal adenocarcinoma (PDAC), aberrant micro RNAs (miRNAs) expression plays a crucial role. This study sought to identify and validate the key miRNAs and potential target genes involved in PDAC. A bioinformatic analysis was conducted to determine their potential use as biomarkers and therapeutic targets. Methods: Gene profiling data sets (GSE41372 and GSE32688) were retrieved from the Gene Expression Omnibus database. Differentially expressed miRNAs (DEMs) with a P value <0.05, and |fold change| >2 was identified. The prognostic value of the DEMs was accessed using the online server Kaplan-Meier plotter. Further, gene ontology terms and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed using DAVID 6.7. The protein-protein interaction analyses were conducted with STRING, and miRNA-hub gene networks were constructed using Cytoscape software. The PDAC cells were transfected with miRNA inhibitors or mimics. Cell Counting Kit-8 assays and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining were used to examine cell proliferation and apoptosis, respectively. Wound-healing assays were performed to evaluate cell migration. Results: Three DEMs (hsa-miR-21-5p, hsa-miR-135b-5p, and hsa-miR-222-3p) were identified. High expression levels of hsa-miR-21-5p, hsa-miR-135b-5p, or hsa-miR-222-3p predicted poor overall survival in PDAC patients. The pathway analysis revealed that the predicted target genes of the DEMs were closely related to several signaling pathways (including 'pathways in cancer', 'miRNAs in cancer', 'platinum drug resistance', 'lipid and atherosclerosis', and 'MAPK signaling pathway'). The MYC proto-oncogene (MYC), phosphate and tensin homolog gene (PTEN), poly(ADP-ribose) polymerase 1 (PARP1), von Hippel-Lindau (VHL), and fork head box p3 (FOXP3) were identified as potential target genes. The inhibition of hsa-miR-21-5p, hsa-miR-135b-5p, or hsa-miR-222-3p expression decreased cell proliferation. The overexpression of hsa-miR-21-5p, hsa-miR-135b-5p, or hsa-miR-222-3p facilitated PDAC cell migration. Conclusions: This study constructed the miRNA-hub gene network, which provides novel insights into the PDAC progression. Although further research is required, our results offer clues for new potential prognostic markers and therapeutic targets of PDAC.

Cathelicidins Target HSP60 To Restrict CVB3 Transmission via Disrupting the Exosome and Reducing Cardiomyocyte Apoptosis.

Cathelicidin antimicrobial peptides (mouse, CRAMP; human, LL-37) have broad-spectrum antiviral activities against enveloped viruses, but their mechanisms of action against nonenveloped viruses remain to be elucidated. Coxsackievirus B3 (CVB3), a member of nonenveloped virus belonging to the Enterovirus genus of Picornaviridae, is an important pathogen of viral myocarditis and dilated cardiomyopathy. Here, we observed that cardiac CRAMP expression was significantly upregulated in mice after CVB3 infection. The administration of CRAMP or LL-37 markedly suppressed CVB3 infection in mice, and CRAMP deficiency increased the susceptibility of mice to CVB3. CRAMP and LL-37 inhibited CVB3 replication in primary cardiomyocytes. However, they did not inactivate CVB3 particles and did not regulate the response of cardiomyocytes against CVB3 infection. Intriguingly, they inhibited CVB3 transmission through the exosome, but not virus receptor. In detail, CRAMP and LL-37 directly induced the lysis of exosomes by interfering with exosomal heat shock protein 60 (HSP60) and then blocked the diffusion of exosomes to recipient cells and inhibited the establishment of productive infection by exosomes. In addition, the interaction of CRAMP and LL-37 with HSP60 simultaneously inhibited HSP60-induced apoptosis in cardiomyocytes and reduced HSP60-enhanced CVB3 replication. Our findings reveal a novel mechanism of cathelicidins against viral infection and provide a new therapeutic strategy for CVB3-induced viral myocarditis. IMPORTANCE The relative mechanisms that cathelicidin antimicrobial peptides use to influence nonenveloped virus infection are unclear. We show here that cathelicidin antimicrobial peptides (CRAMP and LL-37) directly target exosomal HSP60 to destroy exosomes, which in turn block the diffusion of exosomes to recipient cardiomyocytes and reduced HSP60-induced apoptosis, thus restricting coxsackievirus B3 infection. Our results provide new insights into the mechanisms cathelicidin antimicrobial peptides use against viral infection.

miR-9a-5p Protects Ischemic Stroke by Regulating Oxidative Stress and Mitochondrial Autophagy.

Purpose: Present research is aimed at exploring the effect of miR-9a-5p on mitochondrial autophagy and alleviating cellular oxidative stress injury in ischemic stroke. Methods: SH-SY5Y cells were cultured with oxygen-glucose deprivation/reoxygenation (OGD/R) to simulate ischemia/reperfusion. The cells were treated in an anaerobic incubator (95% N2, 5% CO2) for 2 h and then reoxygenated in the normoxic condition for 24 h with 2 ml of normal medium. Cells were transfected with miR-9a-5p mimic/inhibitor or negative control. The RT-qPCR assay was utilized to measure the mRNA expression. Western blot was utilized to evaluate the protein expression. The CCK-8 assay was conducted to detect cell viability. Flow cytometry was applied to examine apoptosis and the cell cycle. The ELISA assay was applied to measure the contents of SOD and MDA in mitochondria. Autophagosomes were observed via electron microscopy. Results: By comparison with the control group, the miR-9a-5p expression in the OGD/R group obviously declined. Mitochondrial crista breaks, vacuole-like changes, and increased autophagosome formation were observed in the OGD/R group. OGD/R injury enhanced oxidative stress damage and mitophagy. When transfected with the miR-9a-5p mimic, mitophagosome production of SH-SY5Y cells decreased and oxidative stress injury was inhibited. However, the miR-9a-5p inhibitor obviously increased mitophagosome production and enhanced oxidative stress injury. Conclusion: miR-9a-5p protects against ischemic stroke by inhibiting OGD/R-induced mitochondrial autophagy and alleviating cellular oxidative stress injury.

Experimental Boson Sampling Enabling Cryptographic One-Way Function.

Boson sampling is a computational problem, which is commonly believed to be a representative paradigm for attaining the milestone of quantum advantage. So far, massive efforts have been made to the experimental large-scale boson sampling for demonstrating this milestone, while further applications of the machines remain a largely unexplored area. Here, we investigate experimentally the efficiency and security of a cryptographic one-way function that relies on coarse-grained boson sampling, in the framework of a photonic boson-sampling machine fabricated by a femtosecond laser direct writing technique. Our findings demonstrate that the implementation of the function requires moderate sample sizes, which can be over 4 orders of magnitude smaller than the ones predicted by the Chernoff bound; whereas for numbers of photons n≥3 and bins d∼poly(m,n), the same output of the function cannot be generated by nonboson samplers. Our Letter is the first experimental study that deals with the potential applications of boson sampling in the field of cryptography and paves the way toward additional studies in this direction.

Exosomes mediate Coxsackievirus B3 transmission and expand the viral tropism.

Specific virus-receptor interactions are important determinants in viral host range, tropism and pathogenesis, influencing the location and initiation of primary infection as well as viral spread to other target organs/tissues in the postviremic phase. Coxsackieviruses of Group B (CVB) and its six serotypes (CVB1-6) specifically interact with two receptor proteins, coxsackievirus-adenovirus receptor (CAR) and decay-accelerating factor (DAF), and cause various lesions in most permissive tissues. However, our previous data and other studies revealed that virus receptor-negative cells or tissues can be infected with CVB type 3 (CVB3), which can also effectively replicate. To study this interesting finding, we explored the possibility that exosomes are involved in CVB3 tropism and that exosomes functionally enhance CVB3 transmission. We found that exosomes carried and delivered CVB3 virions, resulting in efficient infection in receptor-negative host cells. We also found that delivery of CVB3 virions attached to exosomes depended on the virus receptor CAR. Importantly, exosomes carrying CVB3 virions exhibited greater infection efficiency than free virions because they accessed various entry routes, overcoming restrictions to viral tropism. In vivo experiments demonstrated that inhibition of exosome coupling with virions attenuated CVB3-induced immunological system dysfunction and reduced mortality. Our study describes a new mechanism in which exosomes contribute to viral tropism, spread, and pathogenesis.

Enterovirus 71-induced autophagosome fusion with multivesicular bodies facilitates viral RNA packaging into exosomes.

Exosomes have been shown to release from cells infected by viruses and deliver viral particles, genomes, and other viral genetic elements to neighboring cells resulting in modulating host immune response. Our previous study demonstrated that exosomes released from Enterovirus 71 (EV71)-infected cells contained replication-competent EV71 RNA in complex with miR-146a, Ago2, and GW182, which can be successfully transferred to recipient/target cells to establish productive infection. However, the molecular mechanisms that control viral genome package into exosomes are still unclear. In this study, we showed that the EV71-induced autophagy response contributed to viral genome package into exosomes rather than process of exosomes biogenesis. Further study showed that the autophagosomes accumulation facilitated their fusion with MVBs, which resulted in EV71 RNA package into exosome vesicles. Moreover, prevention of autophagosomes-MVBs fusion could abolish this sorting of viral RNA into exosomes. Knockdown of GW182 or Ago2 could weaken the replication ability of exosomal EV71 RNA in recipient cells through decreasing the amount of miR-146a in exosomes, but did not affect the package of viral RNA into exosomes. Our findings strongly suggested that the accumulation of autophagosomes that were induced by EV71 infection play a key role on viral spreading through exosome vesicles.

Factors associated with artificial airway retention after skull base chordoma resection: A retrospective cohort study.

Background: Chordoma is a malignant bone and soft tissue tumor derived from embryonic notochord remnants, and skull base chordoma accounts for ~1/3 of all chordoma cases. Skull base chordoma is closely related to the brainstem and cranial nerves and has a high recurrence rate. The purpose of this study was to investigate the influence of the timing of tracheal extubation on perioperative pulmonary complications. We also aimed to explore predictors of postoperative artificial airway (AA) retention in patients with skull base chordoma. Methods: This was a single-center, retrospective cohort study. The study population included all skull base chordoma patients undergoing surgical treatment between January 2019 and December 2021 at Beijing Tiantan Hospital. The primary outcome was the incidence of postoperative pulmonary complications. Several patient characteristics were evaluated for potential associations with AA retention. Results: A total of 310 patients with skull base chordoma were enrolled. The frequency of AA retention after surgery for skull base chordoma was 30.97%. The incidence of postoperative pulmonary complications was much lower in those without AA retention (3.74 vs. 39.58%, P < 0.001). Factors with the highest point estimates for the odds of AA retention included body mass index, cranial nerve involvement, maximum tumor diameter, operative method, hemorrhage volume, operative duration and intraoperative mechanical ventilation duration. Conclusions: In this retrospective cohort study, most of the factors associated with postoperative airway retention were closely related to the patient's tumor characteristics. These data demonstrate that respiratory management in patients with skull base chordoma remains an ongoing concern.

Association of Gestational Age at Birth With Subsequent Neurodevelopment in Early Childhood: A National Retrospective Cohort Study in China.

Background: The association between preterm birth and neurodevelopmental delays have been well examined, however, reliable estimates for the full range of gestational age (GA) are limited, and few studies explored the impact of post-term birth on child development. Objective: This study aimed to examine the long-term neuropsychological outcomes of children born in a full range of GA with a national representative sample in China. Methods: In this retrospective population-based cohort study, a total of 137,530 preschoolers aged 3-5 years old (65,295/47.5% females and 72,235/52.5% males) were included in the final analysis. The Ages and Stages Questionnaires-Third Edition (ASQ-3) was completed by parents to evaluate children's neurodevelopment. The associations between GA and neurodevelopment were analyzed by a generalized additive mixed model with thin plate regression splines. Logistic regression was also conducted to examine the differences in children's development with different GAs. Results: There was a non-linear relationship between GA and children's neurodevelopmental outcomes with the highest scores at 40 weeks gestational age. The adjusted risks of GAs (very and moderately preterm, late-preterm, early-term, and post-term groups) on suspected developmental delays were observed in communication (OR were 1.83, 1.28, 1.13, and 1.21 respectively, each p < 0.05), gross motor skill (OR were 1.67, 1.38, 1.10, and 1.05 respectively, each p < 0.05), and personal social behavior (OR were 1.01, 1.36, 1.12, and 1.18 respectively, each p < 0.05). The adjusted OR of very and moderately preterm, late-preterm, and early-term were observed in fine motor skills (OR were 1.53, 1.22, and 1.09 respectively, each p < 0.05) and problem-solving (OR were 1.33, 1.12, and 1.06 respectively, each p < 0.05). Conclusion: GAs is a risk factor for neurodevelopmental delays in preschoolers after controlling for a wide range of covariates, and 40-41 weeks may be the ideal delivery GA for optimal neurodevelopmental outcomes. Close observation and monitoring should be considered for early- and post-term born children as well as pre-term children.