Nanozyme-Enhanced Probiotic Spores Regulate the Intestinal Microenvironment for Targeted Acute Gastroenteritis Therapy.

Antibiotic therapeutics to combat intestinal pathogen infections often exacerbate microbiota dysbiosis and impair mucosal barrier functions. Probiotics are promising strategies, because they inhibit pathogen colonization and improve intestinal microbiota imbalance. Nevertheless, their limited targeting ability and susceptibility to oxidative stress have hindered their therapeutic potential. To tackle these challenges, Ces3 is synthesized by in situ growth of CeO2 nanozymes with positive charges on probiotic spores, facilitating electrostatic interactions with negatively charged pathogens and possessing a high reactive oxygen species (ROS) scavenging activity. Importantly, Ces3 can resist the harsh environment of the gastrointestinal tract. In mice with S. Typhimurium-infected acute gastroenteritis, Ces3 shows potent anti-S. Typhimurium activity, thereby alleviating the dissemination of S. Typhimurium into other organs. Additionally, owing to its O2 deprivation capacity, Ces3 promotes the proliferation of anaerobic probiotics, reshaping a healthy intestinal microbiota. This work demonstrates the promise of combining antibacterial, anti-inflammatory, and O2 content regulation properties for acute gastroenteritis therapy.

Berberine ameliorates chronic intermittent hypoxia-induced cardiac remodelling by preserving mitochondrial function, role of SIRT6 signalling.

Chronic intermittent hypoxia (CIH) is associated with an increased risk of cardiovascular diseases. Previously, we have shown that berberine (BBR) is a potential cardioprotective agent. However, its effect and mechanism on CIH-induced cardiomyopathy remain uncovered. This study was designed to determine the effects of BBR against CIH-induced cardiac damage and to explore the molecular mechanisms. Mice were exposed to 5 weeks of CIH with or without the treatment of BBR and adeno-associated virus 9 (AAV9) carrying SIRT6 or SIRT6-specific short hairpin RNA. The effect of BBR was evaluated by echocardiography, histological analysis and western blot analysis. CIH caused the inactivation of myocardial SIRT6 and AMPK-FOXO3a signalling. BBR dose-dependently ameliorated cardiac injury in CIH-induced mice, as evidenced by increased cardiac function and decreased fibrosis. Notably, SIRT6 overexpression mimicked these beneficial effects, whereas infection with recombinant AAV9 carrying SIRT6-specific short hairpin RNA abrogated them. Mechanistically, BBR reduced oxidative stress damage and preserved mitochondrial function via activating SIRT6-AMPK-FOXO3a signalling, enhancing mitochondrial biogenesis as well as PINK1-Parkin-mediated mitophagy. Taken together, these data demonstrate that SIRT6 activation protects against the pathogenesis of CIH-induced cardiac dysfunction. BBR attenuates CIH-induced myocardial injury by improving mitochondrial biogenesis and PINK1-Parkin-dependent mitophagy via the SIRT6-AMPK-FOXO3a signalling pathway.

A patient-based murine model recapitulates human STAT3 gain-of-function syndrome.

STAT3 gain-of-function (GOF) variants results in a heterogeneous clinical syndrome characterized by early onset immunodeficiency, multi-organ autoimmunity, and lymphoproliferation. While 191 documented cases with STAT3 GOF variants have been reported, the impact of individual variants on immune regulation and the broad clinical spectrum remains unclear. We developed a Stat3p.L387R mouse model, mirroring a variant identified in a family exhibiting common STAT3 GOF symptoms, and rare phenotypes including pulmonary hypertension and retinal vasculitis. In vitro experiments revealed increased STAT3 phosphorylation, nuclear migration, and DNA binding of the variant. Our Stat3p.L387R model displayed similar traits from previous Stat3GOF strains, such as splenomegaly and lymphadenopathy. Notably, Stat3p.L387R/+ mice exhibited heightened embryonic lethality compared to prior Stat3GOF/+ models and ocular abnormalities were observed. This research underscores the variant-specific pathology in Stat3p.L387R/+ mice, highlighting the ability to recapitulate human STAT3 GOF syndrome in patient-specific transgenic murine models. Additionally, such models could facilitate tailored treatment development.

Postoperative pain after different doses of remifentanil infusion during anaesthesia: a meta-analysis.

BACKGROUND: This meta-analysis aimed to explore the correlation between the different doses of remifentanil-based anaesthesia and postoperative pain in randomised trials. METHODS: The electronic databases including PubMed, Cochrane, clinical trial registries, and Google Scholar were searched up to November 2022 for randomised controlled trials (RCTs) that assessed the dose dependent efficacy of remifentanil for postoperative pain intensity and hyperalgesia. RESULTS: 31 studies involving 2019 patients were included for analysis. Compared with the high remifentanil dose administration, patients in low doses showed less postoperative pain intensity at 1-2 h (weighted mean differences (WMD): 0.60, 95% CI, 0.05 to 1.15), 3-8 h (WMD: 0.38, 95% CI, 0.00 to 0.75), 24 h (WMD: 0.26, 95% CI, 0.04 to 0.48) and 48 h (WMD: 0.32, 95% CI, 0.09 to 0.55). Remifentanil-free regimen failed to decrease the pain score at 24 h (WMD: 0.10, 95% CI, -0.10 to 0.30) and 48 h (WMD: 0.15, 95% CI, -0.22 to 0.52) in comparison with remifentanil-based anaesthesia. After excluding trials with high heterogeneity, the dose of the remifentanil regimen was closely correlated with the postoperative pain score (P=0.03). In addition, the dose of the remifentanil regimen was not associated with the incidence of postoperative nausea and vomiting (PONV) (P=0.37). CONCLUSIONS: Our meta-analysis reveals that the low dose of remifentanil infusion is recommendable for general anaesthesia maintenance. No evidence suggests that remifentanil-free regimen has superiority in reducing postoperative pain. Moreover, remifentanil doesn't have a dose dependent effect in initiating PONV. TRIAL REGISTRATION: The protocol of present study was registered with PROSPERO (CRD42022378360).

A Novel Method for Rolling Bearing Fault Diagnosis Based on Gramian Angular Field and CNN-ViT.

Fault diagnosis is one of the important applications of edge computing in the Industrial Internet of Things (IIoT). To address the issue that traditional fault diagnosis methods often struggle to effectively extract fault features, this paper proposes a novel rolling bearing fault diagnosis method that integrates Gramian Angular Field (GAF), Convolutional Neural Network (CNN), and Vision Transformer (ViT). First, GAF is used to convert one-dimensional vibration signals from sensors into two-dimensional images, effectively retaining the fault features of the vibration signal. Then, the CNN branch is used to extract the local features of the image, which are combined with the global features extracted by the ViT branch to diagnose the bearing fault. The effectiveness of this method is validated with two datasets. Experimental results show that the proposed method achieves average accuracies of 99.79% and 99.63% on the CWRU and XJTU-SY rolling bearing fault datasets, respectively. Compared with several widely used fault diagnosis methods, the proposed method achieves higher accuracy for different fault classifications, providing reliable technical support for performing complex fault diagnosis on edge devices.

Risk assessment of antimony-arsenic contaminated soil remediated using zero-valent iron at different pH values combined with freeze-thaw cycles.

Soil in mining wastelands is seriously polluted with heavy metals. Zero-valent iron (ZVI) is widely used for remediation of heavy metal-polluted soil because of its excellent adsorption properties; however, the remediation process is affected by complex environmental conditions, such as acid rain and freeze-thaw cycles. In this study, the effects of different pH values and freeze-thaw cycles on remediation of antimony (Sb)- and arsenic (As)-contaminated soil by ZVI were investigated in laboratory simulation experiments. The stability and potential human health risks associated with the remediated soil were evaluated. The results showed that ZVI has a significant stabilizing effect on Sb and As in both acidic and alkaline soils contaminated with dual levels of Sb and As, and the freeze-thaw process in different pH value solution systems further enhances the ability of ZVI to stabilize Sb and As, especially in acidic soils. However, it should be noted that apart from the pH=1.0 solution environment, ZVI's ability to stabilize As is attenuated under other circumstances, potentially leading to leaching of its unstable form and thereby increasing contamination risks. This indicates that the F1 (2% ZVI+pH=1 solution+freeze-thaw cycle) processing exhibits superior effectiveness. After F1 treatment, the bioavailability of Sb and As in both soils also significantly decreased during the gastric and intestinal stages (about 60.00%), the non-carcinogenic and carcinogenic risks of Sb and As in alkaline soils are eliminated for children and adults, with a decrease ranging from 60.00% to 70.00%, while in acidic soil, the non-carcinogenic and carcinogenic risks of As to adults and children is acceptable, but Sb still poses non-carcinogenic risks to children, despite reductions of about 65.00%. These findings demonstrate that soil pH is a crucial factor influencing the efficacy of ZVI in stabilizing Sb and As contaminants during freeze-thaw cycles. This provides a solid theoretical foundation for utilizing ZVI in the remediation of Sb- and As-contaminated soils, emphasizing the significance of considering both pH levels and freeze-thaw conditions to ensure effective and safe treatment.

Prediction of Postoperative Sore Throat in Patients After Day-case Surgery With General Anesthesia: A Retrospective Study.

PURPOSE: Postoperative sore throat (POST) is a major complaint after day-case surgery. The objectives of this study were to investigate the risk factors for POST and develop a stratified nursing model for POST after day-case surgery. DESIGN: This case-control study was conducted at Department of Anesthesiology of 1st Affiliated Hospital of Wenzhou Medical University in Wenzhou, Zhejiang, China. METHODS: Anesthesia records and postanesthesia care files of adult patients undergoing day-case surgery with general anesthesia were reviewed. The primary outcome was the incidence of POST at 24 hours after day-case surgery or before discharge within 24 hours. Multivariate logistics regression was used to identify risk factors for POST. A nomogram was created to predict the probability of POST after day-case surgery. FINDINGS: A total of 9,312 records were retrieved from June 1, 2021 to April 30, 2022, including 8,499 files in the training group and 813 files in the validation group. One thousand five hundred and twenty-five cases in the training group experienced POST. The independent risk factors for POST included: thyroid surgery (odds ratios [OR] = 22.42, 95% confidence intervals [CI]: 18.45 to 27.25), shorter thyromental distance (OR = 1.18, 95% CI: 1.06 to 1.30), smaller neck circumference (OR = 1.09, 95% CI: 1.06 to 1.11), duration of anesthesia (OR = 1.13, 95% CI: 1.04 to 1.22), female (OR = 1.66, 95% CI: 1.41 to 1.96), age (OR = 0.99, 95% CI: 0.99 to 1.00) and the presence of bloody sputum (OR = 8.33, 95% CI: 6.53 to 10.63). A nomogram that involved five factors was established to predict the probability of POST after day-case surgery. The area under the receiver operating characteristic curve in the training and validation groups was 0.77 and 0.81, respectively. The calibration curve demonstrated good consistency between the actual POST and the predicted probability. CONCLUSIONS: The following variables are independently associated with POST: thyroid surgery, age approaching to 40 years old, female, shorter thyromental distance and smaller neck circumference, longer duration of anesthesia, and the presence of bloody sputum. A novel stratified nursing model is feasible for predicting the probability of POST.

Inhibition of ferroptosis by icariin treatment attenuates excessive ethanol consumption-induced atrial remodeling and susceptibility to atrial fibrillation, role of SIRT1.

Ferroptosis contributes to the pathogenesis of atrial fibrillation (AF), although the mechanisms are still largely uncovered. The current study was designed to explore the pharmacological effects of icariin against ethanol-induced atrial remodeling, if any, and the mechanisms involved with a focus on SIRT1 signaling. Excessive ethanol-treated animals were administered with Ferrostatin-1, Erastin or icariin to evaluate the potential effects of icariin or ferroptosis. Then, the underling mechanisms was further explored in the in vitro experiments using HL-1 atrial myocytes. Excessive ethanol administration caused significant atrial damage as evidenced by increased susceptibility to AF, altered atrial conduction pattern, atrial enlargement, and enhanced fibrotic markers. These detrimental effects were reversed by Ferrostatin-1 or icariin treatment, while Erastin co-administration markedly abolished the beneficial actions conferred by icariin. Mechanistically, ethanol-treated atria exhibited markedly up-regulated pro-ferroptotic protein (PTGS2, ACSL4, P53) and suppressed anti-ferroptotic molecules (GPX4, FTH1). Icariin treatment inhibited ethanol-induced atrial ferroptosis by reducing atrial mitochondrial damage, ROS accumulation and iron overload. Interestingly, the in vivo and in vitro data showed that icariin activated atrial SIRT1-Nrf-2-HO-1 signaling pathway, while EX527 not only reversed these effects, but also abolished the therapeutic effects of icariin. Moreover, the stimulatory effects on GPX4, SLC7A11 and the suppressive effects on ACSL4, P53 conferred by icariin were blunted by EX527 treatment. These data demonstrate that ferroptosis plays a causative role in the pathogenesis of ethanol-induced atrial remodeling and susceptibility to AF. Icariin protects against atrial damage by inhibiting ferroptosis via SIRT1 signaling. Its role as a prophylactic/therapeutic drug deserves further clinical study.

Dynamic transcriptome analysis unravels key regulatory genes of maize root growth and development in response to potassium deficiency.

MAIN CONCLUSION: Integrated root phenotypes and transcriptome analysis have revealed key candidate genes responsible for maize root growth and development in potassium deficiency. Potassium (K) is a vital macronutrient for plant growth, but our understanding of its regulatory mechanisms in maize root system architecture (RSA) and K+ uptake remains limited. To address this, we conducted hydroponic and field trials at different growth stages. K+ deficiency significantly inhibited maize root growth, with metrics like total root length, primary root length, width and maximum root number reduced by 50% to 80% during early seedling stages. In the field, RSA traits exhibited maximum values at the silking stage but continued to decline thereafter. Furthermore, K deprivation had a pronounced negative impact on root morphology and RSA growth and grain yield. RNA-Seq analysis identified 5972 differentially expressed genes (DEGs), including 17 associated with K+ signaling, transcription factors, and transporters. Weighted gene co-expression network analysis revealed 23 co-expressed modules, with enrichment of transcription factors at different developmental stages under K deficiency. Several DEGs and transcription factors were predicted as potential candidate genes responsible for maize root growth and development. Interestingly, some of these genes exhibited homology to well-known regulators of root architecture or development in Arabidopsis, such as Zm00001d014467 (AtRCI3), Zm00001d011237 (AtWRKY9), and Zm00001d030862 (AtAP2/ERF). Identifying these key genes helps to provide a deeper understanding of the molecular mechanisms governing maize root growth and development under nutrient deficient conditions offering potential benefits for enhancing maize production and improving stress resistance through targeted manipulation of RSA traits in modern breeding efforts.

Interactions between Phosphorus Enrichment and Nitrification Accelerate Relative Nitrogen Deficiency during Cyanobacterial Blooms in a Large Shallow Eutrophic Lake.

Regime shifts between nitrogen (N) and phosphorus (P) limitation, which trigger cyanobacterial succession, occur in shallow eutrophic lakes seasonally. However, the underlying mechanism is not yet fully illustrated. We provide a novel insight to address this from interactions between sediment P and nitrification through monthly field investigations including 204 samples and microcosm experiments in Lake Chaohu. Total N to P mass ratios (TN/TP) varied significantly across seasons especially during algal bloom in summer, with the average value being 26.1 in June and descending to 7.8 in September gradually, triggering dominant cyanobacterial succession from Microcystis to Dolichospermum. The regulation effect of sediment N/P on water column TN/TP was stronger in summer than in other seasons. Iron-bound P and alkaline phosphatase activity in sediment, rather than ammonium, contributed to the higher part of nitrification. Furthermore, our microcosm experiments confirmed that soluble active P and enzymatic hydrolysis of organic P, accumulating during algal bloom, fueled nitrifiers and nitrification in sediments. These processes promoted lake N removal and led to relative N deficiency in turn. Our results highlight that N and P cycles do not exist independently but rather interact with each other during lake eutrophication, supporting the dual N and P reduction program to mitigate eutrophication in shallow eutrophic lakes.

Experience of using a virtual reality rehabilitation management platform for breast cancer patients: a qualitative study.

PURPOSES: Postoperative rehabilitation of upper limb function is crucial for breast cancer. Therefore, we developed a rehabilitation management platform using virtual reality to improve rehabilitation compliance and effect. The purpose of this research was to understand the user usability experience of breast cancer patients about the postoperative rehabilitation management of upper limb function using virtual reality. METHODS: A qualitative descriptive research was designed. We used a maximum difference purpose sampling method. According to the inclusion and exclusion criteria, a 3-armor hospital in Changchun was selected for the recruitment. A one-on-one semi-structured interviews were conducted with patients after breast cancer operation. The Colaizzi seven-step analysis method was used to classify data under summarized themes. RESULTS: Twenty patients participated in this semi-structured interview. User experience could be summarized into four themes as follows: 1) experience and feeling after using the virtual reality rehabilitation management platform; 2) factors influencing the use of the virtual reality rehabilitation management platform; 3) willingness to recommend the virtual reality rehabilitation management platform to peers; and 4) suggestions to improve the virtual reality rehabilitation management platform. CONCLUSIONS: Breast cancer patients who used the rehabilitation management platform had a good experience, and their recognition and satisfaction were high. The use of the platform is influenced by many factors, and most patients are willing to recommend this platform to their peers. Future studies should be conducted according to patients' feedback and suggestions on how to further optimize and improve the platform.

Not just in sync: Relations between partners' actions influence the sense of joint agency during joint action.

When people perform joint actions together, they often experience a sense of joint agency ("we did that together"). The current study investigated whether relations between partners' actions within joint actions that require precise interpersonal synchrony influence joint agency, above and beyond the degree of synchrony partners achieve. We employed a mixed-methods approach that combined a quantitative experiment with a qualitative analysis of post-experiment interviews. Partners produced synchronized tone sequences that comprised either constant pitch sequences (simple temporal alignment between partners' actions) or musical duets (complex metrical and harmonic relations between partners' actions). Participants reported stronger joint agency for duets than constant pitches, when comparing trials with equally good synchronization. Post-experiment interviews revealed that joint agency was also influenced by participants' knowledge of the music and their perceptions of task performance, difficulty, and enjoyability. These findings further our understanding of joint agency for joint actions that require precise interpersonal synchrony.

Effect of superior laryngeal nerve block in alleviating sore throat after application of i-gel supraglottic airway: a randomized controlled trial.

BACKGROUND: Postoperative sore throat (POST) is a common complaint after supraglottic airway device (SAD) application. Internal branch of the superior laryngeal nerve (iSLN) block has the potential to alleviate POST. The aim of this trial was to explore the effect of iSLN block in alleviating sore throat, as well as to identify the potential risk factors for POST after SAD insertion. METHODS: One hundred thirty-four patients scheduled for elective gynecological surgery were randomized to either group T: tetracaine syrup (1%) for local lubrication on i-gel supraglottic device (n = 67) or group B: i-gel insertion with water based lubricant on it and followed by bilateral iSLN block (ropivacaine, 0.375%, 2 ml for each side) (n = 67). Under ultrasound guidance, iSLN was exposed below thyrohyoid membrane. The primary outcome was the intensity of sore throat at 6 h after surgery. In addition, POST score at 0.5 h and 24 h, the severity of postoperative swallowing discomfort, acoustic analysis and complications were measured. RESULTS: Compared with tetracaine syrup for local lubrication, iSLN block resulted in a reduced intensity of POST at 0.5 h (P = 0.044, OR = 1.99, 95%CI 1.02 to 3.88) and 6 h (P < 0.001, OR = 5.07, 95%CI 2.53 to 10.14) after surgery, as well as less severity of swallowing discomfort (P < 0.001, OR = 2.21, 95%CI 1.63 to 2.99) and cough (P = 0.039, OR = 1.97, 95%CI 1.04 to 3.73). The patients after iSLN block presented lower jitter and shimmer value in acoustic analysis at 6 h after surgery (P < 0.001). CONCLUSIONS: iSLN block was effective in alleviating POST, improving voice function, as well as reducing postoperative swallowing discomfort and coughing. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2000037974) on 8th Sept 2020.

Soil potentially toxic element pollution at different urbanization intensities: Quantitative source apportionment and source-oriented health risk assessment.

Potentially toxic element (PTE) pollution of urban soils has become the focus of social concern, but the differences of the sources, pollution levels and source-oriented human health risks (HHR) of PTE in urban soils among different urban intensity areas is rarely known. This study explored a comprehensive scheme that combined positive matrix factorization model and source-oriented assessment to quantitatively assess the priority pollution sources and HHR in urban soils from areas with different urbanization intensities. All the average values for PTE concentrations, except for Cr, were higher than their corresponding background values. The contributions made by the four sources (atmospheric deposition, agricultural activities, traffic activities, and natural sources) were relatively similar (22.29-29.89%) in the low urbanization intensity (LUI) area, whereas traffic activities and atmospheric deposition made the greatest contributions in the medium urbanization intensity (MUI) (29.12%) and the high urbanization intensity (HUI) (38.97%) areas, respectively. The geo-accumulation index results revealed that Cd was the most polluting element and the HUI area had the highest pollution levels. The content-oriented assessment of HHR demonstrated that the non-carcinogenic risks were acceptable, but the carcinogenic risks were unacceptable. According to the source-oriented HHR assessment, among the anthropogenic activities, atmospheric deposition contributed the most to carcinogenic risk of children in all areas, and atmospheric deposition, traffic activities and agricultural activities contributed the most to the carcinogenic risk of adults in HUI, MUI and LUI, respectively. This suggest that control measures need to be tailored to the appropriate urbanization intensity to effectively curb PTE pollution caused by anthropogenic activities.

Effect of transnasal humidified rapid-insufflation ventilatory exchange on gastric insufflation during anaesthesia induction: A randomised controlled trial and multivariate analysis.

BACKGROUND: Mask ventilation during anaesthesia induction is generally used to provide adequate oxygenation but improper mask ventilation can result in gastric insufflation. It has been reported that oxygen administered by transnasal humidified rapid-insufflation ventilatory exchange (THRIVE) during anaesthesia induction can maintain oxygenation but its effect on gastric insufflation is unknown. OBJECTIVES: The primary aim of this study was to evaluate whether THRIVE provided adequate oxygenation without gastric insufflation. The secondary aim was to explore the change in cross-sectional area of the antrum (CSAa) during anaesthesia induction. Other potential risk factors of gastric insufflation were also explored. DESIGN: A prospective, randomised, double-blind study. SETTING: Single centre, Department of Anaesthesiology, 1 st Affiliated Hospital, Wenzhou Medical University, China, from May 2022 to September 2022. PATIENTS: A total of 210 patients (age >18 years, ASA classification I to III) scheduled to undergo general anaesthesia were enrolled. INTERVENTIONS: For induction of general anaesthesia, patients were randomised into two groups: THRIVE and pressure-controlled facemask ventilation (PCFV). The THRIVE group received high-flow nasal oxygen with no additional ventilation. The PCFV group had pressure-controlled positive pressure ventilation from the anaesthesia machine via a tight fitting facemask. Gastric insufflation was detected using real-time ultrasonography. The CSAa was measured from ultrasonography images obtained before anaesthesia induction and at 0, 1, 2 and 3 min after loss of consciousness. MAIN OUTCOME MEASURES: The incidence of gastric insufflation during the period from loss of consciousness until intubation. RESULTS: The THRIVE group had a lower incidence of gastric insufflation during anaesthesia induction than the PCFV group (13.0 vs. 35.3%, odds ratio (OR) = 0.27, 95% confidence interval (CI), 0.14 to 0.56, P  < 0.001). Increase in the CSA after anaesthesia induction was significantly correlated with gastric insufflation (OR = 5.35, 95% CI, 2.90 to 9.89, P  < 0.001). Multivariate logistic regression analysis showed that advancing age (OR = 1.04, 95% CI, 1.01 to 1.07), obstructive sleep apnoea syndrome (OR = 2.43, 95% CI, 1.24 to 4.76), higher Mallampati score (OR = 2.66, 95% CI, 1.21 to 5.85) and PCFV (OR = 4.78, 95% CI, 2.06 to 11.06) were important independent risk factors for gastric insufflation. CONCLUSION: During anaesthesia induction, the THRIVE technique provided adequate oxygenation with a reduced incidence of gastric insufflation. PCFV, advancing age, obstructive sleep apnoea syndrome and the Mallampati score were found to be independent risk factors for gastric insufflation during anaesthesia induction. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR200059555.

Integrated Cascade Nanozymes with Antisenescence Activities for Atherosclerosis Therapy.

Senescent cells are the critical drivers of atherosclerosis formation and maturation. Mitigating senescent cells holds promise for the treatment of atherosclerosis. In an atherosclerotic plaque microenvironment, senescent cells interact with reactive oxygen species (ROS), promoting the disease development. Here, we hypothesize that a cascade nanozyme with antisenescence and antioxidant activities can serve as an effective therapeutic for atherosclerosis. An integrated cascade nanozyme with superoxide dismutase- and glutathione peroxidase-like activities, named MSe1 , is developed in this work. The obtained cascade nanozyme can attenuate human umbilical vein endothelial cell (HUVEC) senescence by protecting DNA from damage. It significantly weakens inflammation in macrophages and HUVECs by eliminating overproduced intracellular ROS. Additionally, the MSe1 nanozyme effectively inhibits foam cell formation in macrophages and HUVECs by decreasing the internalization of oxidized low-density lipoprotein. After intravenous administration, the MSe1 nanozyme significantly inhibits the formation of atherosclerosis in apolipoprotein E-deficient (ApoE-/- ) mice by reducing oxidative stress and inflammation and then decreases the infiltration of inflammatory cells and senescent cells in atherosclerotic plaques. This study not only provides a cascade nanozyme but also suggests that the combination of antisenescence and antioxidative stress holds considerable promise for treating atherosclerosis.

Photoinduced Transition-Metal-Free Chan-Evans-Lam-Type Coupling: Dual Photoexcitation Mode with Halide Anion Effect.

Herein, we report a photoinduced transition-metal-free C(aryl)-N bond formation between 2,4,6-tri(aryl)boroxines or arylboronic acids as an aryl source and 1,4,2-dioxazol-5-ones (dioxazolones) as an amide coupling partner. Chloride anion, either generated in situ by photodissociation of chlorinated solvent molecules or added separately as an additive, was found to play a critical cooperative role, thereby giving convenient access to a wide range of synthetically versatile N-arylamides under mild photo conditions. The synthetic virtue of this transition-metal-free Chan-Evans-Lam-type coupling was demonstrated by large-scale reactions, synthesis of 15N-labeled arylamides, and applicability toward biologically relevant compounds. On the basis of mechanistic investigations, two distinctive photoexcitations are proposed to function in the current process, in which the first excitation involving chloro-boron adduct facilitates the transition-metal-free activation of dioxazolones by single electron transfer (SET), and the second one enables the otherwise-inoperative 1,2-aryl migration of the thus-formed N-chloroamido-borate adduct.

Did variants in inborn errors of immunity genes contribute to the extinction of Neanderthals?

BACKGROUND: Neanderthals were a species of archaic humans that became extinct around 40,000 years ago. Modern humans have inherited 1-6% of Neanderthal DNA as a result of interbreeding. These inherited Neanderthal genes have paradoxical influences, while some can provide protection to viral infections, some others are associated with autoimmune/auto-inflammatory diseases. OBJECTIVE: We aim to investigate whether genetic variants with strong detrimental effects on the function of the immune system could have potentially contributed to the extinction of the Neanderthal population. METHODS: We used the publically available genome information from an Altai Neanderthal and filtered for potentially damaging variants present in genes associated with inborn errors of immunity (IEI) and checked whether these variants were present in the genomes of the Denisovan, Vindija and Chagyrskaya Neanderthals. RESULTS: We identified 24 homozygous variants and 15 heterozygous variants in IEI-related genes in the Altai Neanderthal. Two homozygous variants in the UNC13D gene and one variant in the MOGS gene were present in all archaic genomes. Defects in the UNC13D gene are known to cause a severe and often fatal disease called hemophagocytic lymphohistiocystosis (HLH). One of these variants p.(N943S) has been reported in patients with HLH. Variants in MOGS are associated with glycosylation defects in the immune system affecting the susceptibility for infections. CONCLUSIONS: Although the exact functional impact of these three variants needs further elucidation, we speculate that they could have resulted in an increased susceptibility to severe diseases and may have contributed to the extinction of Neanderthals after exposure to specific infections.

Hope and symptom burden of women with breast cancer undergoing chemotherapy: A cross-sectional study.

AIM: This research aimed to explore the level of hope and symptom burden of breast cancer women undergoing chemotherapy, and predictive factors of hope were also investigated. BACKGROUND: Chemotherapy brings physical and psychological stress to breast cancer patients. As an effective coping strategy, hope gives them the courage to overcome difficulties and improve prognosis and survival. Therefore, efforts are needed to raise hope. DESIGN/METHODS: A total of 450 women who were undergoing breast cancer chemotherapy participated in this cross-sectional study. Sociodemographic data, disease characteristics, and measures of hope and symptom burden were collected using questionnaires. Hope was assessed using the validated Herth Hope Index, and the previously validated Memorial Symptom Assessment Scale was used to assess symptom burden. This paper adhered to the STROBE guidelines. RESULTS: Chinese breast cancer chemotherapy women hope average scores of 30.15 ± 4.82 were in the medium range of the Hearth Hope Index as specified by Herth to be 24-35. Patients with age ≤45, religious beliefs and lighter symptom burden have a higher level of hope. These variables explained a total of 22.9% of the variation in hope. CONCLUSIONS: The level of hope for women undergoing breast cancer chemotherapy still needs to be further improved. Symptom burden can negatively predict hope. RELEVANCE TO CLINICAL PRACTICE: If nurses can decrease breast cancer chemotherapy women symptom burden, there is an impact on increasing levels of hope.

Coupled relationships among anammox, denitrification, and dissimilatory nitrate reduction to ammonium along salinity gradients in a Chinese estuarine wetland.

Salinization in estuarine wetlands significantly alters the balance between their nitrogen (N) removal and retention abilities but these processes have not yet been characterized effectively. In the present study, the potential rates of sediment denitrification, anaerobic ammonium oxidation (anammox), and dissimilatory nitrate reduction to ammonium (DNRA) were mapped using N isotope tracing methods along salinity gradients across the Yellow River Delta wetland (YRDW) in China. The contribution of anammox to total dissimilatory N transformations in YRDW was merely 6.8%, whereas denitrification and DNRA contributed 52.3% and 40.9%, respectively. The potential rate of denitrification (5.82 µmol/kg/h) decreased significantly along salinity gradients and markedly exceeded DNRA potential rate (2.7 µmol/kg/h) in fresh wetlands, but was lower than that of DNRA in oligohaline wetlands (3.06 and 3.18 µmol/kg/h, respectively). Moreover, a significantly positive relationship between salinity and DNRA/denitrification was obeserved, indicating that increased salinity may favor DNRA over denitrification. Furthermore, total sulfur (TS) content and ratio of total organic carbon to total nitrogen (C/N) increased with the salinity gradient and showed evident positive relationships with the DNRA/denitrification ratio. In this study, we proved that increased salinization resulted in the dominance of DNRA over denitrification, possible through the addition of S and alteration of the C/N in estuarine wetlands, leading to increased N retention in estuarine wetlands during salinization, which would enhance the eutrophication potential within wetlands and in downstream ecosystems.