Predicting the immunity landscape and prognosis with an NCLs signature in liver hepatocellular carcinoma.

BACKGROUND: Activated neutrophils release depolymerized chromatin and protein particles into the extracellular space, forming reticular Neutrophil Extracellular Traps (NETs). This process is accompanied by programmed inflammatory cell death of neutrophils, known as NETosis. Previous reports have demonstrated that NETosis plays a significant role in immune resistance and microenvironmental regulation in cancer. This study sought to characterize the function and molecular mechanism of NETosis-correlated long non-coding RNAs (NCLs) in the prognostic treatment of liver hepatocellular carcinoma (LIHC). METHODS: We obtained the transcriptomic and clinical data from The Cancer Genome Atlas (TCGA) and evaluated the expression of NCLs in LIHC. A prognostic signature of NCLs was constructed using Cox and Last Absolute Shrinkage and Selection Operator (Lasso) regression, while the accuracy of model was validated by the ROC curves and nomogram, etc. In addition, we analyzed the associations between NCLs and oncogenic mutation, immune infiltration and evasion. Finally, LIHC patients were classified into four subgroups based on consensus cluster analysis, and drug sensitivity was predicted. RESULTS: After screening, we established a risk model combining 5 hub-NCLs and demonstrated its reliability. Independence checks suggest that the model may serve as an independent predictor of LIHC prognosis. Enrichment analysis revealed a concentration of immune-related pathways in the high-risk group. Immune infiltration indicates that immunotherapy could be more effective in the low-risk group. Upon consistent cluster analysis, cluster subgroup 4 presented a better prognosis. Sensitivity tests showed the distinctions in therapeutic effectiveness among various drugs in different subgroups. CONCLUSION: Overall, we have developed a prognostic signature that can discriminate different LIHC subgroups through the 5 selected NCLs, with the objective of providing LIHC patients a more precise, personalized treatment regimen.

A retrospective study on the effect of Chinese patent medicine combined with conventional treatment on the survival outcomes of 313 patients with stage II-III NSCLC.

PURPOSE: We aim to explore the effect of Chinese Patent Medicine (CPM), including Huisheng oral solution (HSOS) on the 4-year survival rate of patients with stage II and III non-small cell lung cancer, and assess the association between blood coagulation indicators and survival outcomes. MATERIALS AND METHODS: 313 patients diagnosed with stage II and III NSCLC were collected during 2015-2016. Kaplan-Meier method and Cox proportional hazard model were applied to analyze the factors affecting the 4-year survival rate of patients. RESULTS: According to the effect of CPM, the medicine prescribed in this study could be classified into two types. The proportion of patients who received "Fuzheng Quyu" CPM for more than three months was higher than the proportion of patients who received other two types of CPM for more than three months. Medical records of 313 patients with NSCLC were analyzed. 4-year survival rate for patients received CPM more than 6 months and 3 months were higher than those received CPM less than 3 months (P = 0.028 and P = 0.021 respectively. In addition, 4-year survival rate for patients who received HSOS for more than 3 months was higher than those who received HSOS for less than 3 months (P = 0.041). Patients with elevated preoperative fibrinogen (FIB) level and those without surgery had an increased mortality risk (HR = 1.98, P < 0.01, and HR = 2.76, P < 0.01 respectively). CONCLUSION: The medium and long-term use of CPM/HSOS was positively associated with higher survival rate in NSCLC patients. Patients with high-level preoperative FIB level and those without surgery might have a poor prognosis in the following years.

Insight into the fracture energy dissipation mechanism in elastomer composites via sacrificial bonds and fillers.

Most tough elastomer composites are reinforced by introducing sacrificial structures and fillers. Understanding the contribution of fillers and sacrificial bonds in elastomer composites to the energy dissipation is critical for the design of high-toughness materials. However, the energy dissipation mechanism in elastomer composites remains elusive. In this study, using a tearing test and time-temperature superposition, we investigate the effect of fillers and sacrificial bonds on the energy dissipation of elastomer composites consisting of poly(lipoic acid)/silver-coated Al fillers. We found that the fillers and sacrificial bonds mutually enhance both the intrinsic fracture energy and the bulk energy dissipation, and moreover the sacrificial bonds play a more important role in enhancing fracture toughness than the fillers. It is unreasonable to rely solely on the loss factor for bulk energy dissipation. The addition of sacrificial bonds results in a chain segment experiencing greater binding force compared to the addition of fillers. This suggests that the chain segment consumes more energy during its movement. By calculating the length of the Kuhn chain segment and the Kuhn number, it is evident that the addition of sacrificial bonds results in a greater binding force for the chain segment than the addition of fillers, and this enhanced binding force increases the energy consumption during the motion of the chain segment.

Anti-Proteolytic Peptide R7I Protects the Intestinal Barrier and Alleviates Fatty Acid Malabsorption in Salmonella typhimurium-Infected Mice.

With a wide range of hosts, environmental adaptation, and antibiotic resistance, Salmonella typhimurium is one of the most common causes of food poisoning in the world. Infection with Salmonella typhimurium not only results in intestinal inflammation but also damages the intestinal barrier and interferes with the host's ability to absorb nutrients. It is imperative to find alternatives to antibiotics for eradicating bacteria, reducing intestinal damage, and reestablishing nutrient absorption, especially given that antibiotics are currently prohibited. This research aims to understand the protective role of anti-proteolytic peptide R7I on the gut in the setting of Salmonella typhimurium infection and its impact on nutritional absorption, maybe offering an alternative to antibiotics for bacterial killing. The findings demonstrated that R7I reduced the production of inflammatory factors, including IL-6, TNF-α, and L-1ß in the jejunum and decreased the expression of genes like TLR4 and NF-κB in the jejunum (p < 0.05). R7I enhanced antioxidant capacity and preserved the antioxidant/pro-oxidant balance in the jejunum (p < 0.05). R7I also normalized intestinal shape and restored tight junction protein expression. Fatty acid binding protein 2 (FABP2) and fatty acid transport protein 4 (FATP4) expression in the jejunum was restored by R7I. In addition, serum-free fatty acids and lipid metabolites were significantly higher in the R7I group than in the control group (p < 0.05). Overall, the anti-enzyme peptide R7I maintained the healthy state of the intestine and alleviated the abnormal fatty acid absorption caused by bacterial infection.

Oxygen enrichment protects against intestinal damage and gut microbiota disturbance in rats exposed to acute high-altitude hypoxia.

Acute high-altitude hypoxia can lead to intestinal damage and changes in gut microbiota. Sustained and reliable oxygen enrichment can resist hypoxic damage at high altitude to a certain extent. However, it remains unclear whether oxygen enrichment can protect against gut damage and changes in intestinal flora caused by acute altitude hypoxia. For this study, eighteen male Sprague-Dawley rats were divided into three groups, control (NN), hypobaric hypoxic (HH), and oxygen-enriched (HO). The NN group was raised under normobaric normoxia, whereas the HH group was placed in a hypobaric hypoxic chamber simulating 7,000 m for 3 days. The HO group was exposed to oxygen-enriched air in the same hypobaric hypoxic chamber as the HH group for 12 h daily. Our findings indicate that an acute HH environment caused a fracture of the crypt structure, loss of epithelial cells, and reduction in goblet cells. Additionally, the structure and diversity of bacteria decreased in richness and evenness. The species composition at Phylum and Genus level was characterized by a higher ratio of Firmicutes and Bacteroides and an increased abundance of Lactobacillus with the abundance of Prevotellaceae_NK3B31_group decreased in the HH group. Interestingly, after oxygen enrichment intervention, the intestinal injury was significantly restrained. This was confirmed by an increase in the crypt depth, intact epithelial cell morphology, increased relative density of goblet cells, and higher evenness and richness of the gut microbiota, Bacteroidetes and Prevotellaceae as the main microbiota in the HO group. Finally, functional analysis showed significant differences between the different groups with respect to different metabolic pathways, including Amino acid metabolism, energy metabolism, and metabolism. In conclusion, this study verifies, for the first time, the positive effects of oxygen enrichment on gut structure and microbiota in animals experiencing acute hypobaric hypoxia.

Drug in Therapeutic Polymer: Sinomenine-Loaded Oxidation-Responsive Polymeric Nanoparticles for Rheumatoid Arthritis Treatment.

Rheumatoid arthritis (RA) is a chronic inflammatory joint disease that frequently involves cartilage damage and the destruction of the bone structure, ultimately resulting in disability and long-term pain. It is clear that overexpression of reactive oxygen species (ROS) and the complex inflammatory microenvironment are the main causes of RA pathogenesis; thereby, the efficacy of any single-drug treatment is limited. Herein, we formulated a therapeutic hyaluronic acid derivative (PAM-HA) with adsorption capacity to the subchondral bone, a long retention time within inflamed joints, and ROS-scavenging capacity, which was used as a drug carrier for realizing the controlled release of sinomenine (Sin) within arthritic joints. This "drug in therapeutic polymer" design strategy was aimed at realizing antioxidant and anti-inflammatory combination therapy for RA. In vivo experiments suggest that PAM-HA@Sin NPs can be retained in the inflamed joints of rats for a long time compared with commercially available free Sin injections. As expected, therapeutic PAM-HA polymeric carriers can increase joint lubrication and reduce oxidative stress, while the released Sin induces downregulation of proinflammatory factors (TNF-α and IL-1ß) and upregulation of anti-inflammatory factors (Arg-1 and IL-10) via the NF-κB pathway. In summary, a ROS-scavenging hyaluronic acid (HA) derivative was developed as the nanocarrier for Sin delivery to simultaneously remodel the oxidative/inflammatory microenvironment in RA, which opens up new horizons for the development of therapeutic polymers and the combined therapeutic strategies.

Unveiling Interfacial Effects for Efficient and Stable Hydrogen Evolution Reaction on Ruthenium Nanoparticles-Embedded Pentlandite Composites.

Heterogenous catalysis is important for future clean and sustainable energy systems. However, an urgent need to promote the development of efficient and stable hydrogen evolution catalysts still exists. In this study, ruthenium nanoparticles (Ru NPs) are in situ grown on Fe5 Ni4 S8 support (Ru/FNS) by replacement growth strategy. An efficient Ru/FNS electrocatalyst with enhanced interfacial effect is then developed and successfully applied for pH-universal hydrogen evolution reaction (HER). The Fe vacancies formed by FNS during the electrochemical process are found to be conducive to the introduction and firm anchoring of Ru atoms. Compared to Pt atoms, Ru atoms get easily aggregated and then grow rapidly to form NPs. This induces more bonding between Ru NPs and FNS, preventing the fall-off of Ru NPs and maintaining the structural stability of FNS. Moreover, the interaction between FNS and Ru NPs can adjust the d-band center of Ru NPs, as well as balance the hydrolytic dissociation energy and hydrogen binding energy. Consequently, the as-prepared Ru/FNS electrocatalyst exhibits excellent HER activity and improved cycle stability under pH-universal conditions. The developed pentlandite-based electrocatalysts with low cost, high activity, and good stability are promising candidates for future applications in water electrolysis.

Active-site-enriched dendritic crystal Co/Fe-doped Ni3S2 electrocatalysts for efficient oxygen evolution reaction.

The electrochemical decomposition of water plays a critical role in green and sustainable energy. However, the development of efficient and low-cost non-noble metal catalysts to overcome the high potential of the anodic oxygen evolution reaction (OER) is still challenging. In this work, electrocatalysts with high OER activity were obtained by doping Co/Fe bimetals into Ni3S2 (CF-NS) via a simple single-step hydrothermal method by adjusting the doping ratio of bimetals. A series of characterization studies revealed that the introduction of a Co/Fe co-dopant increased the number of active sites and improved the electroconductibility, while optimizing the electronic structure of Ni3S2. Meanwhile, Fe-induced high valence Ni contributed to the production of an OER active phase NiOOH. The unique dendritic crystal morphology facilitated the disclosure of the active sites and the expansion of mass transfer channels. The optimized sample required a low overpotential of 146 mV to obtain a current density of 10 mA cm-2 in 1.0 M KOH solution. The optimized sample also operated stably for at least 86 h. In sum, the proposed method looks very promising for designing efficient, stable, and low-cost non-precious metal catalysts with high conductivity and multiple active sites, useful for future synthesis of transition metal sulfide catalysts.

Controlled Decompression Alleviates Motor Dysfunction by Regulating Microglial Polarization via the HIF-1α Signaling Pathway in Intracranial Hypertension.

Decompressive craniectomy (DC) is a major form of surgery that is used to reduce intracranial hypertension (IH), the most frequent cause of death and disability following severe traumatic brain injury (sTBI) and stroke. Our previous research showed that controlled decompression (CDC) was more effective than rapid decompression (RDC) with regard to reducing the incidence of complications and improving outcomes after sTBI; however, the specific mechanisms involved have yet to be elucidated. In the present study, we investigated the effects of CDC in regulating inflammation after IH and attempted to identify the mechanisms involved. Analysis showed that CDC was more effective than RDC in alleviating motor dysfunction and neuronal death in a rat model of traumatic intracranial hypertension (TIH) created by epidural balloon pressurization. Moreover, RDC induced M1 microglia polarization and the release of pro-inflammatory cytokines. However, CDC treatment resulted in microglia primarily polarizing into the M2 phenotype and induced the significant release of anti-inflammatory cytokines. Mechanistically, the establishment of the TIH model led to the increased expression of hypoxia-inducible factor-1α (HIF-1α); CDC ameliorated cerebral hypoxia and reduced the expression of HIF-1α. In addition, 2-methoxyestradiol (2-ME2), a specific inhibitor of HIF-1α, significantly attenuated RDC-induced inflammation and improved motor function by promoting M1 to M2 phenotype transformation in microglial and enhancing the release of anti-inflammatory cytokines. However, dimethyloxaloylglycine (DMOG), an agonist of HIF-1α, abrogated the protective effects of CDC treatment by suppressing M2 microglia polarization and the release of anti-inflammatory cytokines. Collectively, our results indicated that CDC effectively alleviated IH-induced inflammation, neuronal death, and motor dysfunction by regulating HIF-1α-mediated microglial phenotype polarization. Our findings provide a better understanding of the mechanisms that underlie the protective effects of CDC and promote clinical translational research for HIF-1α in IH.

Electromagnetic fields ameliorate hepatic lipid accumulation and oxidative stress: potential role of CaMKKß/AMPK/SREBP-1c and Nrf2 pathways.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide, and is related to disturbed lipid metabolism and redox homeostasis. However, a definitive drug treatment has not been approved for this disease. Studies have found that electromagnetic fields (EMF) can ameliorate hepatic steatosis and oxidative stress. Nevertheless, the mechanism remains unclear. METHODS: NAFLD models were established by feeding mice a high-fat diet. Simultaneously, EMF exposure is performed. The effects of the EMF on hepatic lipid deposition and oxidative stress were investigated. Additionally, the AMPK and Nrf2 pathways were analysed to confirm whether they were activated by the EMF. RESULTS: Exposure to EMF decreased the body weight, liver weight and serum triglyceride (TG) levels and restrained the excessive hepatic lipid accumulation caused by feeding the HFD. The EMF boosted CaMKKß protein expression, activated AMPK phosphorylation and suppressed mature SREBP-1c protein expression. Meanwhile, the activity of GSH-Px was enhanced following an increase in nuclear Nrf2 protein expression by PEMF. However, no change was observed in the activities of SOD and CAT. Consequently, EMF reduced hepatic reactive oxygen species (ROS) and MDA levels, which means that EMF relieved liver damage caused by oxidative stress in HFD-fed mice. CONCLUSIONS: EMF may activate the CaMKKß/AMPK/SREBP-1c and Nrf2 pathways to control hepatic lipid deposition and oxidative stress. This investigation indicates that EMF may be a novel therapeutic method for NAFLD.

A nomogram for predicting the risk of poor prognosis in patients with poor-grade aneurysmal subarachnoid hemorrhage following microsurgical clipping.

Objective: Aneurysmal subarachnoid hemorrhage (aSAH) is a common and potentially fatal cerebrovascular disease. Poor-grade aSAH (Hunt-Hess grades IV and V) accounts for 20-30% of patients with aSAH, with most patients having a poor prognosis. This study aimed to develop a stable nomogram model for predicting adverse outcomes at 6 months in patients with aSAH, and thus, aid in improving the prognosis. Method: The clinical data and imaging findings of 150 patients with poor-grade aSAH treated with microsurgical clipping of intracranial aneurysms on admission from December 2015 to October 2021 were retrospectively analyzed. Least absolute shrinkage and selection operator (LASSO), logistic regression analyses, and a nomogram were used to develop the prognostic models. Receiver operating characteristic (ROC) curves and Hosmer-Lemeshow tests were used to assess discrimination and calibration. The bootstrap method (1,000 repetitions) was used for internal validation. Decision curve analysis (DCA) was performed to evaluate the clinical validity of the nomogram model. Result: LASSO regression analysis showed that age, Hunt-Hess grade, Glasgow Coma Scale (GCS), aneurysm size, and refractory hyperpyrexia were potential predictors for poor-grade aSAH. Logistic regression analyses revealed that age (OR: 1.107, 95% CI: 1.056-1.116, P < 0.001), Hunt-Hess grade (OR: 8.832, 95% CI: 2.312-33.736, P = 0.001), aneurysm size (OR: 6.871, 95% CI: 1.907-24.754, P = 0.003) and refractory fever (OR: 3.610, 95% CI: 1.301-10.018, P < 0.001) were independent predictors of poor outcome. The area under the ROC curve (AUC) was 0.909. The calibration curve and Hosmer-Lemeshow tests showed that the nomogram had good calibration ability. Furthermore, the DCA curve showed better clinical utilization of the nomogram. Conclusion: This study provides a reliable and valuable nomogram that can accurately predict the risk of poor prognosis in patients with poor-grade aSAH after microsurgical clipping. This tool is easy to use and can help physicians make appropriate clinical decisions to significantly improve patient prognosis.

Machine Learning Prediction Algorithm for In-Hospital Mortality following Body Contouring.

BACKGROUND: Body contouring is a common procedure, but it is worth attention because of concern for a variety of complications, and even the potential for death. As a result, the purpose of this study was to determine the key predictors following body contouring and create models for the risk of mortality using diverse machine learning (ML) models. METHODS: The National Inpatient Sample database from 2015 to 2017 was queried to identify patients undergoing body contouring. Candidate predictors, such as demographics, comorbidities, personal history, postoperative complications, and operative features, were included. The outcome was in-hospital mortality. Models were compared by area under the curve, accuracy, sensitivity, specificity, positive and negative predictive values, and decision curve analysis. RESULTS: Overall, 8214 patients undergoing body contouring were identified, among whom 141 (1.72%) died in the hospital. Variable importance plot demonstrated that sepsis was the variable with greatest importance across all ML algorithms, followed by Elixhauser Comorbidity Index, cardiac arrest, and so forth. The naive Bayes model had a higher predictive performance (area under the curve, 0.898; 95% CI, 0.884 to 0.911) among these eight ML models. Similarly, in the decision curve analysis, the naive Bayes model also demonstrated a higher net benefit (ie, the correct classification of in-hospital deaths considering a tradeoff between false-negatives and false-positives) compared with the other seven models across a range of threshold probability values. CONCLUSION: The ML models, as indicated by this study, can be used to predict in-hospital death for patients at risk who undergo body contouring.

Acetylated α-tubulin alleviates injury to the dendritic spines after ischemic stroke in mice.

BACKGROUND AND AIM: Functional recovery is associated with the preservation of dendritic spines in the penumbra area after stroke. Previous studies found that polymerized microtubules (MTs) serve a crucial role in regulating dendritic spine formation and plasticity. However, the mechanisms that are involved are poorly understood. This study is designed to understand whether the upregulation of acetylated α-tubulin (α-Ac-Tub, a marker for stable, and polymerized MTs) could alleviate injury to the dendritic spines in the penumbra area and motor dysfunction after ischemic stroke. METHODS: Ischemic stroke was mimicked both in an in vivo and in vitro setup using middle cerebral artery occlusion and oxygen-glucose deprivation models. Thy1-YFP mice were utilized to observe the morphology of the dendritic spines in the penumbra area. MEC17 is the specific acetyltransferase of α-tubulin. Thy1 CreERT2-eYFP and MEC17fl/fl mice were mated to produce mice with decreased expression of α-Ac-Tub in dendritic spines of pyramidal neurons in the cerebral cortex. Moreover, AAV-PHP.B-DIO-MEC17 virus and tubastatin A (TBA) were injected into Thy1 CreERT2-eYFP and Thy1-YFP mice to increase α-Ac-Tub expression. Single-pellet retrieval, irregular ladder walking, rotarod, and cylinder tests were performed to test the motor function after the ischemic stroke. RESULTS: α-Ac-Tub was colocalized with postsynaptic density 95. Although knockout of MEC17 in the pyramidal neurons did not affect the density of the dendritic spines, it significantly aggravated the injury to them in the penumbra area and motor dysfunction after stroke. However, MEC17 upregulation in the pyramidal neurons and TBA treatment could maintain mature dendritic spine density and alleviate motor dysfunction after stroke. CONCLUSION: Our study demonstrated that α-Ac-Tub plays a crucial role in the maintenance of the structure and functions of mature dendritic spines. Moreover, α-Ac-Tub protected the dendritic spines in the penumbra area and alleviated motor dysfunction after stroke.

Temporal trends and outcomes in acute ischaemic stroke patients with a current or historical diagnosis of cancer.

BACKGROUND AND PURPOSE: The aim was to evaluate the temporal trends, characteristics and in-hospital outcomes of patients hospitalized with acute ischaemic stroke (AIS) between those with and without current or historical malignancies. METHODS: Adult hospitalizations with a primary diagnosis of AIS were identified from the National Inpatient Sample database 2007-2017. Logistic regression was used to compare the differences in the utilization of AIS interventions and in-hospital outcomes. For further analysis, subgroup analyses were performed stratified by cancer subtypes. RESULTS: There were 892,862 hospitalizations due to AIS, of which 108,357 (12.14%) had a concurrent diagnosis of current cancer (3.41%) or historical cancer (8.72%). After adjustment for confounders, patients with current malignancy were more likely to have worse clinical outcomes. The presence of historical cancers was not associated with an increase in poor clinical outcomes. Additionally, AIS patients with current malignancy were less likely to receive intravenous thrombolysis (adjusted odds ratio 0.66, 95% confidence interval 0.63-0.71). Amongst the subgroups of AIS patients treated with intravenous thrombolysis or mechanical thrombectomy, outcomes varied by cancer types. Notably, despite these acute stroke interventions, outcome remains poor in AIS patients with lung cancer. CONCLUSIONS: Although AIS patients with malignancy generally have worse in-hospital outcomes versus those without, there were considerable variations in these outcomes according to different cancer types and the use of AIS interventions. Finally, treatment of these AIS patients with a current or historical cancer diagnosis should be individualized.

3D Talking Face With Personalized Pose Dynamics.

Recently, we have witnessed a boom in applications for 3D talking face generation. However, most existing 3D face generation methods can only generate 3D faces with a static head pose, which is inconsistent with how humans perceive faces. Only a few articles focus on head pose generation, but even these ignore the attribute of personality. In this article, we propose a unified audio-driven approach to endow 3D talking faces with personalized pose dynamics. To achieve this goal, we establish an original person-specific dataset, providing corresponding head poses and face shapes for each video. Our framework is composed of two separate modules: PoseGAN and PGFace. Given an input audio, PoseGAN first produces a head pose sequence for the 3D head, and then, PGFace utilizes the audio and pose information to generate natural face models. With the combination of these two parts, a 3D talking head with dynamic head movement can be constructed. Experimental evidence indicates that our method can generate person-specific head pose sequences that are in sync with the input audio and that best match with the human experience of talking heads.

Mild hypothermia alleviates early brain injury after subarachnoid hemorrhage via suppressing pyroptosis through AMPK/NLRP3 inflammasome pathway in rats.

As a subtype of stroke, subarachnoid hemorrhage (SAH) has a notoriously high rate of disability and mortality owing to the lack of effective intervention. Early brain injury (EBI) is the main factor responsible for the dismal prognosis of SAH patients. The current study intends to explore the molecular mechanism underlying the effect of MH on EBI after SAH from a novel perspective of pyroptosis, a highly specific inflammatory programmed cell death, in the SAH rat model. Sprague-Dawley (SD) rats were divided into different groups in accordance with various treatments. In the treatment group, the rats underwent mild hypothermia for 4 h after modeling; in the inhibitor group, Compound C (an inhibitor of AMPK) was administered intravenous injections (i.v.) 30 min before modeling. Neurological score, neuronal death, brain water content, inflammatory reaction, and expression levels of pyroptosis-related proteins were evaluated in the rats. Our results indicate that the MH therapy significantly increased the neurological score and assuaged brain edema, neuronal injury, and inflammatory reaction induced by SAH. Meanwhile, MH therapy upregulated the level of AMPK phosphorylation whereas downregulated the protein expressions of NLRP3, ASC, cleaved caspase-1, GSDMD, IL-1ß, and IL-18. The reversed effect of MH therapy by Compound C concretely indicated that MH therapy inhibited pyroptosis through an AMPK-dependent pathway. Our study also found that MH therapy potently curbed the increasing trend of brain temperature (BT), rectal temperature (RT), and ICP after SAH. Taken together, our data indicate that the neuroprotective effects of MH therapy were manifested by inhibiting pyroptosis via the AMPK/NLRP3 inflammasome pathway, which may serve as a promising therapy for the intervention of SAH.

Keratin 18 Depletion as a Possible Mechanism for the Induction of Apoptosis and Ferroptosis in the Rat Hippocampus After Hypobaric Hypoxia.

Memory impairment is one of the neuropsychological effects of hypobaric hypoxia (HH), which can be associated with programmed cell death, such as apoptosis and ferroptosis. Emerging evidence indicates crosstalk between apoptosis and ferroptosis, while the crosstalk between HH-induced apoptosis and ferroptosis in the hippocampus has not been clarified. Here, microarray profiles were extracted to analyze the differentially expressed genes with and without HH exposure, and keratin 18 (Krt18) was found to be a potential gene related to both apoptosis and ferroptosis. Then, we conducted morphological observations that showed that apoptosis and ferroptosis coexisted in the rat hippocampus after HH exposure. Combined with the real-time q-PCR analysis, the mRNA expression of Krt18 decreased significantly after HH exposure for 1 day and 3 days, and Mapk10 (JNK3) was upregulated at the corresponding time points. After exposure for 7 days, Krt18 and JNK3 showed no significant change. In conclusion, Krt18 may regulate apoptosis and ferroptosis simultaneously, possibly via the JNK signaling pathway, which might provide a potential central target for apoptosis and ferroptosis in hippocampal injury after HH exposure.

The machine learning model based on trajectory analysis of ribonucleic acid test results predicts the necessity of quarantine in recurrently positive patients with SARS-CoV-2 infection.

Background: SARS-CoV-2 patients re-experiencing positive nucleic acid test results after recovery is a concerning phenomenon. Current pandemic prevention strategy demands the quarantine of all recurrently positive patients. This study provided evidence on whether quarantine is required in those patients, and predictive algorithms to detect subjects with infectious possibility. Methods: This observational study recruited recurrently positive patients who were admitted to our shelter hospital between May 12 and June 10, 2022. The demographic and epidemiologic data was collected, and nucleic acid tests were performed daily. virus isolation was done in randomly selected cases. The group-based trajectory model was developed based on the cycle threshold (Ct) value variations. Machine learning models were validated for prediction accuracy. Results: Among the 494 subjects, 72.04% were asymptomatic, and 23.08% had a Ct value under 30 at recurrence. Two trajectories were identified with either rapid (92.24%) or delayed (7.76%) recovery of Ct values. The latter had significantly higher incidence of comorbidities; lower Ct value at recurrence; more persistent cough; and more frequently reported close contacts infection compared with those recovered rapidly. However, negative virus isolation was reported in all selected samples. Our predictive model can efficiently discriminate those with delayed Ct value recovery and infectious potentials. Conclusion: Quarantine seems to be unnecessary for the majority of re-positive patients who may have low transmission risks. Our predictive algorithm can screen out the suspiciously infectious individuals for quarantine. These findings may assist the enaction of SARS-CoV-2 pandemic prevention strategies regarding recurrently positive patients in the future.

Improved Catalytic Activity and Stability of Co9S8 by Se Incorporation for Efficient Oxygen Evolution Reaction.

Combining an excellent electrocatalytic activity with the good structural stability of Co9S8 remains challenging for the oxygen evolution reaction (OER). In this study, density functional theory was used to demonstrate the importance of moderate adsorption strength with *O and *OOH intermediate species on Co9S8 for achieving excellent electrocatalytic performances. A novel strategy was proposed to effectively optimize the *O oxidation to *OOH by introducing Se heteroatoms to adjust adsorption of the two intermediates. This process also allowed prediction of the simultaneous enhancement of the structural stability of Co9S8 due to the weak electronegativity of a Se dopant. The experimental results demonstrated that Se doping can regulate the charge density of Co2+ and Co3+ in Co9S8-xSex, leading to a substantially improved OER performance of Co9S8-xSex. As a result, our Co9S6.91Se1.09 electrode exhibited an overpotential of 271 mV at 10 mA cm-2 in a 1.0 M KOH solution. In particular, it also demonstrated an excellent stability (∼120 h) under a current density of 10 mA cm-2, indicating the potential for practical applications. Overall, the proposed strategy looks promising for regulating the electronic structures and improving the electrochemical performances of sulfide materials.

Mental fatigue decreases complexity: Evidence from multiscale entropy analysis of instantaneous frequency variation in alpha rhythm.

Mental fatigue (MF) jeopardizes performance and safety through a variety of cognitive impairments and according to the complexity loss theory, should represent "complexity loss" in electroencephalogram (EEG). However, the studies are few and inconsistent concerning the relationship between MF and loss of complexity, probably because of the susceptibility of brain waves to noise. In this study, MF was induced in thirteen male college students by a simulated flight task. Before and at the end of the task, spontaneous EEG and auditory steady-state response (ASSR) were recorded and instantaneous frequency variation (IFV) in alpha rhythm was extracted and analyzed by multiscale entropy (MSE) analysis. The results show that there were significant differences in IFV in alpha rhythm either from spontaneous EEG or from ASSR for all subjects. Therefore, the proposed method can be effective in revealing the complexity loss caused by MF in spontaneous EEG and ASSR, which may serve as a promising analyzing method to mark mild mental impairments.