Biological significance of METTL5 in atherosclerosis: comprehensive analysis of single-cell and bulk RNA sequencing data.

BACKGROUND: N6-methyladenosine (m6A) methylation is involved in the pathogenesis of atherosclerosis (AS). Limited studies have examined the role of the m6A methyltransferase METTL5 in AS pathogenesis. METHODS: This study subjected the AS dataset to differential analysis and weighted gene co-expression network analysis to identify m6A methylation-associated differentially expressed genes (DEGs). Next, the m6A methylation-related DEGs were subjected to consensus clustering to categorize AS samples into distinct m6A subtypes. Single-cell RNA sequencing (scRNA-seq) analysis was performed to investigate the proportions of each cell type in AS and adjacent healthy tissues and the expression levels of key m6A regulators. The mRNA expression levels of METTL5 in AS and healthy tissues were determined using quantitative real-time polymerase chain reaction (qRT-PCR) analysis. RESULTS: AS samples were classified into two subtypes based on a five-m6A regulator-based model. scRNA-seq analysis revealed that the proportions of T cells, monocytes, and macrophages in AS tissues were significantly higher than those in healthy tissues. Additionally, the levels of m6A methylation were significantly different between AS and healthy tissues. METTL5 expression was upregulated in macrophages, smooth muscle cells (SMCs), and endothelial cells (ECs). qRT-PCR analysis demonstrated that the METTL5 mRNA level in AS tissues was downregulated when compared with that in healthy tissues. CONCLUSIONS: METTL5 is a potential diagnostic marker for AS subtypes. Macrophages, SMCs, and ECs, which exhibit METTL5 upregulation, may modulate AS progression by regulating m6A methylation levels.

A Novel NIR Fluorescence Probe with AIE Property to Image Viscosity in Nystatin-Induced Cell Model.

As one of the most significant parameters in cellular microenvironment, viscosity levels could be used to determine the metabolic process of bioactive substances within cells. Abnormal viscosity levels are closely associated with a series of diseases. Therefore, the design and synthesis of fluorescent probes that can monitor changes of intracellular viscosity in real-time is of great significance for the study of disease development process. Here, a new viscosity-recognized NIR fluorescence probe W1 based on quinoline-malonitrile is synthesized, and it is not susceptible to interference substances. Besides, AIE probe W1 shows fast response, excellent photostability, low cytotoxicity, good linear relationship between fluorescence intensity value and viscosity. Based on the above advantages, probe W1 is used to image the change of viscosity level in the cell model induced by nystatin.

Modeling and anti-sway control method for vertical lift-up/lay-down process of slender-beam payload.

The existing crane control methods mainly aim at suppressing the oscillation of the payloads during the transportation process. However, during the vertical lift-up/lay-down process of the slender-beam payload (SBP), such as the installation of the wind turbine towers, rocket assembly, and pipeline laying, one end of the SBP is lifted up and the other end is in contact with the ground. In this situation, the external disturbance may cause the SBP to sway around the contact point. In this paper, a nonlinear three-dimensional dynamic model for the vertical lift-up/lay-down process of the SBP is established. On this basis, a control method for suppressing oscillation during the lift-up/lay-down process of the SBP is proposed by adopting the non-singular terminal sliding mode control (NTSMC). The stability of the NTSMC is proved based on the Lyapunov method. Simulations and experiments are carried out to verify the effectiveness of the proposed method.

Development and validation of a scale for the assessment of the knowledge-attitude-practice of parents towards children snoring.

BACKGROUND: Children Snoring is a common childhood disorder that affects the growth and development of children and is detrimental to their health. Increasing awareness of Children Snoring among parents is important. AIM: To develop the Knowledge-Attitude-Practice of Parents towards Children Snoring Scale and test the reliability and validity of the scale. METHODS: The development of the tool was divided into two phases involving 1257 parents from China. In the first phase, an initial project bank was created through a literature review. This was followed by a Delphi expert consultation, group discussion and pre-survey. The second stage screened the items and conducted an exploratory factor analysis, then conducted a confirmatory factor analysis and tested for reliability and validity. RESULTS: Support was found for the 25-item Knowledge-Attitude-Practice toward Children Snoring scale. Exploratory and confirmatory factor analyses provide support for four subscales: (parental basic cognition toward Children Snoring; parents' perception of complications of Children Snoring; parents' attitude towards Children Snoring; parents' concern and prevention of Children Snoring). Internal consistency for the total scale was high (Cronbach's α = 0.93). The intraclass correlation coefficient of test-retest reliability was 0.92 (95%CI: 0.85 to 0.95), which provided support for the stability of the scale. CONCLUSION: The Knowledge-Attitude-Practice of Parents towards Children Snoring scale shows promise as a measure that may be used by medical workers and community children's health managers.

Financial toxicity of informal caregivers of colorectal cancer patients: A cross-sectional study.

PURPOSE: To assess the level of financial toxicity of informal caregivers of colorectal cancer patients and explore the related key influencing factors. METHOD: A descriptive survey design was used in this study. Data were collected from 236 informal caregivers of colorectal cancer patients between March 2023 and July 2023 from a major hospital in central China (Henan province). Potential influence factors of financial toxicity, including basic information, perceived stress, and social support were analyzed using multivariate linear regression. RESULTS: The financial toxicity score of 236 caregivers of colorectal cancer patients was 19.42 ± 9.72. One hundred and fourteen caregivers (accounting for 48.31%) of colorectal cancer patients had high levels of financial toxicity. Financial toxicity scores of caregivers were negatively correlated with perceived stress (r = -0.421, P < 0.001) and positively correlated with social support (r = 0.416, P < 0.001). Our multivariate regression analysis identified some factors that directly affected caregivers' financial toxicity, including caregiver age (t = 2.105, P = 0.036), medical insurance (t = 2.462, P = 0.015), average household income (t = 2.995, P = 0.003), place of residence (t = 2.872, P = 0.004), perceived stress (t = -4.945, P < 0.001), and social support (t = 4.513, P < 0.001). CONCLUSIONS: Caregivers of colorectal cancer patients generally experience a higher level of financial toxicity, which could be eased by lower perceived stress and higher social support. In clinical practice, it is necessary to comprehensively assess the level of financial toxicity of particular caregivers and enact targeted interventions such as increasing communication and actively providing information to address the high medical costs, reducing the detrimental effects of financial toxicity, and improving the quality of colorectal cancer care.

ViromeFlowX: a Comprehensive Nextflow-based Automated Workflow for Mining Viral Genomes from Metagenomic Sequencing Data.

Understanding the link between the human gut virome and diseases has garnered significant interest in the research community. Extracting virus-related information from metagenomic sequencing data is crucial for unravelling virus composition, host interactions, and disease associations. However, current metagenomic analysis workflows for viral genomes vary in effectiveness, posing challenges for researchers seeking the most up-to-date tools. To address this, we present ViromeFlowX, a user-friendly Nextflow workflow that automates viral genome assembly, identification, classification, and annotation. This streamlined workflow integrates cutting-edge tools for processing raw sequencing data for taxonomic annotation and functional analysis. Application to a dataset of 200 metagenomic samples yielded high-quality viral genomes. ViromeFlowX enables efficient mining of viral genomic data, offering a valuable resource to investigate the gut virome's role in virus-host interactions and virus-related diseases.

Lactate promoted cisplatin resistance in NSCLC by modulating the m6A modification-mediated FOXO3/MAGI1-IT1/miR-664b-3p/IL-6R axis.

BACKGROUND: Cisplatin resistance is one of the major obstacles in non-small cell lung cancer (NSCLC) treatment. Intriguingly, elevated lactate levels were observed in cisplatin-resistant cells, which spurred further investigation into their underlying biological mechanisms. METHODS: Lactate levels were measured by lactate detection kit. Cisplatin-resistance NSCLC cells were established using progressive concentration of cisplatin. Cell viability, proliferation, and apoptosis were detected by CCK-8, EdU, and flow cytometry, respectively. Cell proliferation in vivo was determined by immunohistochemistry of Ki67 and apoptotic cells were calculated by the TUNEL. MeRIP-PCR was used to measure FOXO3 m6A levels. The interactions of genes were analyzed via RIP, ChIP, Dual-luciferase reporter, and RNA pull-down, respectively. RESULTS: Elevated lactate levels were observed in both NSCLC patients and cisplatin-resistance cells. Lactate treatment increased cisplatin-resistance cell viability in vitro and promoted tumor growth in vivo. Mechanistically, lactate downregulated FOXO3 by YTHDF2-mediated m6A modification. FOXO3 transcriptionally reduced MAGI1-IT1 expression. FOXO3 overexpression inhibited the lactate-induced promotion of cisplatin resistance in NSCLC, which were reversed by MAGI1-IT1 overexpression. MAGI1-IT1 and IL6R competitively bound miR-664b-3p. FOXO3 overexpression or MAGI1-IT1 knockdown repressed lactate-mediated cisplatin resistance in vivo. CONCLUSION: Lactate promoted NSCLC cisplatin resistance through regulating FOXO3/MAGI1-IT1/miR-664b-3p/IL6R axis in YTHDF2-mediated m6A modification.

Characterization of neuromuscular transmission and projections of muscle motor neurons in the rat stomach.

The stomach is the primary reservoir of the gastrointestinal tract, where ingested content is broken down into small particles. Coordinated relaxation and contraction is essential for rhythmic motility and digestion, but how the muscle motor innervation is organized to provide appropriate graded regional control is not established. In this study, we recorded neuromuscular transmission to the circular muscle using intracellular microelectrodes to investigate the spread of the influence of intrinsic motor neurons. In addition, microanatomical investigations of neuronal projections and pharmacological analysis were conducted to investigate neuromuscular relationships. We found that inhibitory neurotransmission to the circular muscle is graded with stimulus strength and circumferential distance from the stimulation site. The influence of inhibitory neurons declined between 1 and 11 mm from the stimulation site. In the antrum, corpus, and fundus, the declines at 11 mm were about 20%, 30%, and 50%, respectively. Stimulation of inhibitory neurons elicited biphasic hyperpolarizing potentials often followed by prolonged depolarizing events in the distal stomach, but only hyperpolarizing events in the proximal stomach. Excitatory neurotransmission influence varied greatly between proximal stomach, where depolarizing events occurred, and distal stomach, where no direct electrical effects in the muscle were observed. Structural studies using microlesion surgeries confirmed a dominant circumferential projection. We conclude that motor neuron influences extend around the gastric circumference, that the effectiveness can be graded by the recruitment of different numbers of motor neuron nerve terminals to finely control gastric motility, and that the ways in which the neurons influence the muscle differ between anatomical regions.NEW & NOTEWORTHY This study provides a detailed mapping of nerve transmission to the circular muscle of the different anatomical regions of rat stomach. It shows that excitatory and inhibitory influences extend around the gastric circumference and that there is a summation of neural influence that allows for finely graded control of muscle tension and length. Nerve-mediated electrical events are qualitatively and quantitatively different between regions, for example, excitatory neurons have direct effects on fundus but not antral muscle.

Comparative efficacy of early TIPS, Non-early TIPS, and Standard treatment in patients with cirrhosis and acute variceal bleeding: a network meta-analysis.

BACKGROUND: Cirrhosis is a chronic disease characterized by chronic liver inflammation and diffuse fibrosis. A combination of vasoactive drugs, preventive antibiotics, and endoscopy is the recommended standard treatment for patients with acute variceal bleeding; however, this has been challenged. We compared the effects of early transjugular intrahepatic portosystemic shunt (TIPS), non-early TIPS, and standard treatment in patients with cirrhosis and acute variceal bleeding. MATERIALS AND METHODS: The present network meta-analysis was conducted in accordance with the criteria outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Assessing the methodological quality of systematic reviews guidelines. The review has been registered with the International Prospective Register of Systematic Reviews. The PubMed, Embase, Cochrane Library, ClinicalTrials.gov, and World Health Organization-approved trial registry databases were searched for randomized controlled trials (RCTs) evaluating early TIPS, non-early TIPS, and standard treatment in patients with cirrhosis and acute variceal bleeding. RESULTS: Twenty-four RCTs (1894 patients) were included in the review. Compared with standard treatment, early TIPS [odds ratio (OR), 0.53; 95% credible interval (Cr), 0.30-0.94; surface under the cumulative ranking curve (SUCRA), 98.3] had a lower risk of all-cause mortality (moderate-to-high-quality evidence), and early TIPS (OR, 0.19; 95% CrI, 0.11-0.28; SUCRA, 98.2) and non-early TIPS (OR, 0.30; 95% CrI, 0.23-0.42; SUCRA, 1.8) were associated with a lower risk of rebleeding (moderate-to-high-quality evidence). Early TIPS was not associated with a reduced risk of hepatic encephalopathy, and non-early TIPS (OR, 2.78; 95% CrI, 1.89-4.23, SUCRA, 0) was associated with an increased incidence of hepatic encephalopathy (moderate-to-high-quality evidence). There was no difference in the incidence of new or worsening ascites (moderate-to-high-quality evidence) among the three interventions. CONCLUSION: Based on the moderate-to-high quality evidence presented in this study, early TIPS placement was associated with reduced all-cause mortality [with a median follow-up of 1.9 years (25th-75th percentile range 1.9-2.3 years)] and rebleeding compared to standard treatment and non-early TIPS. Although early TIPS and standard treatment had a comparable incidence of hepatic encephalopathy, early TIPS showed superiority over non-early TIPS in this aspect. Recent studies have also shown promising results in controlling TIPS-related hepatic encephalopathy. However, it is important to consider individual patient characteristics and weigh the potential benefits against the risks associated with early TIPS. Therefore, we recommend that clinicians carefully evaluate the patient's condition, considering factors such as severity of variceal bleeding, underlying liver disease, and overall clinical status, before making a treatment decision. Further well-designed RCTs comparing early TIPS with non-early TIPS are needed to validate these findings and provide more definitive guidance.

Neural regulation of slow waves and phasic contractions in the distal stomach: a mathematical model.

Objective.Neural regulation of gastric motility occurs partly through the regulation of gastric bioelectrical slow waves (SWs) and phasic contractions. The interaction of the tissues and organs involved in this regulatory process is complex. We sought to infer the relative importance of cellular mechanisms in inhibitory neural regulation of the stomach by enteric neurons and the interaction of inhibitory and excitatory electrical field stimulation.Approach.A novel mathematical model of gastric motility regulation by enteric neurons was developed and scenarios were simulated to determine the mechanisms through which enteric neural influence is exerted. This model was coupled to revised and extended electrophysiological models of gastric SWs and smooth muscle cells (SMCs).Main results.The mathematical model predicted that regulation of contractile apparatus sensitivity to intracellular calcium in the SMC was the major inhibition mechanism of active tension development, and that the effect on SW amplitude depended on the inhibition of non-specific cation currents more than the inhibition of calcium-activated chloride current (kiNSCC= 0.77 vs kiAno1= 0.33). The model predicted that the interaction between inhibitory and excitatory neural regulation, when applied with simultaneous and equal intensity, resulted in an inhibition of contraction amplitude almost equivalent to that of inhibitory stimulation (79% vs 77% decrease), while the effect on frequency was overall excitatory, though less than excitatory stimulation alone (66% vs 47% increase).Significance.The mathematical model predicts the effects of inhibitory and excitatory enteric neural stimulation on gastric motility function, as well as the effects when inhibitory and excitatory enteric neural stimulation interact. Incorporation of the model into organ-level simulations will provide insights regarding pathological mechanisms that underpin gastric functional disorders, and allow forin silicotesting of the effects of clinical neuromodulation protocols for the treatment of these disorders.

Attenuation of allergen-specific immunotherapy for atopic dermatitis by ectopic colonization of Brevundimonas vesicularis in the intestine.

Allergen-specific immunotherapy (AIT) has shown beneficial effects against atopic dermatitis (AD); however, the mechanisms and parameters underlying the efficacy of AIT remain unclear. Here, we report that the community structure and function of the oral and gut microbiota are changed in patients with AD undergoing AIT. Transplantation of fecal microbiota from patients who respond well to AIT improves AD-like dermatitis in mice. The abundance of Brevundimonas vesicularis in the gut of AD patients has been found to be positively correlated with disease severity and is decreased following AIT. Furthermore, we find that B. vesicularis from the oral cavity might ectopically colonize the gut of AD patients. In AD model mice, meanwhile, B. vesicularis promotes the skewing of the Treg/Th17 balance toward Th17 polarization and attenuates the efficacy of ovalbumin-specific immunotherapy. Our findings provide potential strategies for the optimization of AIT for AD via the modulation of the gut microbiota.

The Effects of Laughter Yoga on Perceived Stress, Positive Psychological Capital, and Exercise Capacity in Lung Cancer Chemotherapy Patients: A Pilot Randomized Trial.

BACKGROUND: Lung cancer is the malignant tumor with the highest morbidity and mortality rate in China. Although chemotherapy is effective in improving clinical symptoms, it causes a variety of acute and chronic side effects, seriously aggravating the psychological stress of patients. Laughter Yoga as a new type of aerobic exercise can effectively reduce stress levels and increase positive mood in patients. This study aimed to examine the effects of laughter yoga on perceived stress, positive psychological capital, and exercise capacity in lung cancer patients. METHODS: This study was a randomized, single-blind, parallel-group trial. The study enrolled 84 lung cancer chemotherapy patients from a general hospital in central China. These patients were randomly allocated to control and intervention groups (n = 42 per group) after baseline assessments. Patients in the control group received routine care and those in the intervention group received laughter yoga intervention. Perceived stress, positive psychological capital, and exercise capacity were assessed at baseline, immediately post-intervention. RESULTS: During the implementation of the study, there were 2 dropouts in each of the intervention and control groups. Ultimately, 80 patients in the control and intervention groups completed the trial. Patients who received laughter yoga intervention had significantly higher scores in positive psychological capital (P < .01, Cohen's d = 0.692) and exercise capacity (P < .01, Cohen's d = 0.659). Discernible differences were also observed in perceived stress (P < .01, Cohen's d = 1.087) between the 2 groups. CONCLUSIONS: The results of this study suggest that laughter yoga is an effective way and may produce beneficial effects on perceived stress, positive psychological capital and exercise capacity.

Allogeneic Hematopoietic Stem Cell Transplantation Can Improve Prognosis of Extramedullary Infiltration Positive t(8;21) Acute Myeloid Leukemia.

BACKGROUND In t(8;21) acute myeloid leukemia (AML), patients with extramedullary infiltration (EMI) tend to have worse survival outcomes than those without EMI. However, it is still unclear whether allogeneic hematopoietic stem cell transplantation (allo-HSCT) benefits EMI-positive t(8;21) AML patients. MATERIAL AND METHODS This study retrospectively enrolled 651 t(8;21) AML patients, and analyzed 51 patients with EMI at diagnosis. Among the 51 patients, 15 patients received allo-HSCT. RESULTS The incidence of EMI in t(8;21) AML was 10.0%, and the first complete remission rate was 78.5% in EMI-positive t(8;21) AML patients. The central nervous system was the most frequently involved site (29.4%), followed by bones (15.7%), and skin (9.8%). In terms of karyotype, 19 (37.3%) patients were t(8;21) alone, 12 (23.5%) had additional loss of a sex chromosome, and 5 (9.8%) had complex karyotype. Significantly better overall survival was observed in patients with allo-HSCT compared to patients without allo-HSCT in both multivariable models (HR=0.32; P=0.0122) and the Kaplan-Meier curves (P=0.0157). CONCLUSIONS Allo-HSCT improved the survival of EMI-positive t(8;21) AML.

Reassessing endothelial-to-mesenchymal transition in mouse bone marrow: insights from lineage tracing models.

Endothelial cells (ECs) and bone marrow stromal cells (BMSCs) play crucial roles in supporting hematopoiesis and hematopoietic regeneration. However, whether ECs are a source of BMSCs remains unclear. Here, we evaluate the contribution of endothelial-to-mesenchymal transition to BMSC generation in postnatal mice. Single-cell RNA sequencing identifies ECs expressing BMSC markers Prrx1 and Lepr; however, this could not be validated using Prrx1-Cre and Lepr-Cre transgenic mice. Additionally, only a minority of BMSCs are marked by EC lineage tracing models using Cdh5-rtTA-tetO-Cre or Tek-CreERT2. Moreover, Cdh5+ BMSCs and Tek+ BMSCs show distinct spatial distributions and characteristic mesenchymal markers, suggestive of their origination from different progenitors rather than CDH5+ TEK+ ECs. Furthermore, myeloablation induced by 5-fluorouracil treatment does not increase Cdh5+ BMSCs. Our findings indicate that ECs hardly convert to BMSCs during homeostasis and myeloablation-induced hematopoietic regeneration, highlighting the importance of using appropriate genetic models and conducting careful data interpretation in studies concerning endothelial-to-mesenchymal transition.

Comparative effectiveness and safety of laser, needle, and "quick fenestrater" in in situ fenestration during thoracic endovascular aortic repair.

Background: Special instruments are needed for the revascularization of aortic branches in in situ fenestration during thoracic endovascular aortic repair (TEVAR). This prospective study compared the effectiveness and safety of three currently used fenestraters: laser, needle, and Quick Fenestrater (QF). Methods: In all, 101 patients who underwent TEVAR for aortic disease (dissection, n = 62; aneurysm, n = 16, or ulcer, n = 23) were enrolled. All patients were randomly assigned to three groups: 34 were assigned to laser fenestration, 36 to needle fenestration, and 31 to QF fenestration. The epidemiological data, treatment, imaging findings, and follow-up outcomes were analyzed using data from the medical records. Results: The technical success rates of the laser, needle, and QF fenestration groups were 94.1%, 94.4%, and 100% (p > 0.05). After correction of mixed factors such as age and gender, it was showed the average operative time (Laser group: 130.01 ± 9.36 min/ Needle group: 149.80 ± 10.18 min vs. QF group: 101.10 ± 6.75 min, p < 0.001), fluoroscopy time (Laser group: 30.16 ± 9.81 min/ Needle group: 40.20 ± 9.91 min vs. QF group: 19.91 ± 5.42 min, p < 0.001), fenestration time (Laser group 5.50 ± 3.10 min / Needle group 3.50 ± 1.50 min vs. QF group 0.67 ± 0.06 min, p < 0.001), and guide wire passage time after fenestration (Laser group 5.10 ± 1.70 min / Needle group 4.28 ± 1.60 min vs. QF group 0.07 ± 0.01 min, p < 0.001) were all shorter with QF fenestration than with the other two tools. The overall perioperative complication rates of the laser, needle, and QF fenestration groups were 5.9%, 5.6%, and 0% (p > 0.05): One case of sheath thermal injury and one case of vertebral artery ischemia occurred in the laser fenestration group; one case each of access site hematoma and brachial artery thrombosis were reported in the needle fenestration group. 89 (88.1%, 89/101) patients were followed for a median of 12.6 ± 1.6 months. The overall postoperative complication rates of the laser, needle, and QF fenestration groups were 3.3%, 6.5%, and 0% (p > 0.05): In the laser fenestration group, there was one death due to postoperative ST-segment elevation myocardial infarction; in the needle fenestration group, one patient developed occlusion of the bridge stent; no complications occurred in the QF group. Conclusion: All three fenestration methods were effective in reconstructing supra-arch artery during TEVAR. QF fenestration required less contrast agent, with a shorter surgery duration and fewer complications than laser and needle fenestration.

In vivo tracing of the ascending vagal projections to the brain with manganese enhanced magnetic resonance imaging.

Introduction: The vagus nerve, the primary neural pathway mediating brain-body interactions, plays an essential role in transmitting bodily signals to the brain. Despite its significance, our understanding of the detailed organization and functionality of vagal afferent projections remains incomplete. Methods: In this study, we utilized manganese-enhanced magnetic resonance imaging (MEMRI) as a non-invasive and in vivo method for tracing vagal nerve projections to the brainstem and assessing their functional dependence on cervical vagus nerve stimulation (VNS). Manganese chloride solution was injected into the nodose ganglion of rats, and T1-weighted MRI scans were performed at both 12 and 24 h after the injection. Results: Our findings reveal that vagal afferent neurons can uptake and transport manganese ions, serving as a surrogate for calcium ions, to the nucleus tractus solitarius (NTS) in the brainstem. In the absence of VNS, we observed significant contrast enhancements of around 19-24% in the NTS ipsilateral to the injection side. Application of VNS for 4 h further promoted nerve activity, leading to greater contrast enhancements of 40-43% in the NTS. Discussion: These results demonstrate the potential of MEMRI for high-resolution, activity-dependent tracing of vagal afferents, providing a valuable tool for the structural and functional assessment of the vagus nerve and its influence on brain activity.

A hub gene signature as a therapeutic target and biomarker for sepsis and geriatric sepsis-induced ARDS concomitant with COVID-19 infection.

Background: COVID-19 and sepsis represent formidable public health challenges, characterized by incompletely elucidated molecular mechanisms. Elucidating the interplay between COVID-19 and sepsis, particularly in geriatric patients suffering from sepsis-induced acute respiratory distress syndrome (ARDS), is of paramount importance for identifying potential therapeutic interventions to mitigate hospitalization and mortality risks. Methods: We employed bioinformatics and systems biology approaches to identify hub genes, shared pathways, molecular biomarkers, and candidate therapeutics for managing sepsis and sepsis-induced ARDS in the context of COVID-19 infection, as well as co-existing or sequentially occurring infections. We corroborated these hub genes utilizing murine sepsis-ARDS models and blood samples derived from geriatric patients afflicted by sepsis-induced ARDS. Results: Our investigation revealed 189 differentially expressed genes (DEGs) shared among COVID-19 and sepsis datasets. We constructed a protein-protein interaction network, unearthing pivotal hub genes and modules. Notably, nine hub genes displayed significant alterations and correlations with critical inflammatory mediators of pulmonary injury in murine septic lungs. Simultaneously, 12 displayed significant changes and correlations with a neutrophil-recruiting chemokine in geriatric patients with sepsis-induced ARDS. Of these, six hub genes (CD247, CD2, CD40LG, KLRB1, LCN2, RETN) showed significant alterations across COVID-19, sepsis, and geriatric sepsis-induced ARDS. Our single-cell RNA sequencing analysis of hub genes across diverse immune cell types furnished insights into disease pathogenesis. Functional analysis underscored the interconnection between sepsis/sepsis-ARDS and COVID-19, enabling us to pinpoint potential therapeutic targets, transcription factor-gene interactions, DEG-microRNA co-regulatory networks, and prospective drug and chemical compound interactions involving hub genes. Conclusion: Our investigation offers potential therapeutic targets/biomarkers, sheds light on the immune response in geriatric patients with sepsis-induced ARDS, emphasizes the association between sepsis/sepsis-ARDS and COVID-19, and proposes prospective alternative pathways for targeted therapeutic interventions.

Effects of nitrification and urease inhibitors on ammonia-oxidizing microorganisms, denitrifying bacteria, and greenhouse gas emissions in greenhouse vegetable fields.

Soil microorganisms and N cycling are important components of biogeochemical cycling processes. In addition, the study of the effects of nitrification and urease inhibitors on N and microorganisms in greenhouse vegetable fields is essential to reducing N loss and greenhouse gas emissions. The effects of nitrification inhibitors [2-chloro-6-(trichloromethyl) pyridine (CP), dicyandiamide (DCD)], and urease inhibitor [N-(n-butyl) thiophosphoric triamide (NBPT)] on soil inorganic N (NH4+-N, NO2--N and NO3--N) concentrations and the production rates of greenhouse gases (N2O, CH4, and CO2) in greenhouse vegetable fields were investigated via indoor incubation experiments. Polymerase chain reaction amplification and high-throughput sequencing technology (Illumina Miseq) were used to explore the community structure and abundance changes of ammonia-oxidizing archaea (AOA), ammonia-oxidizing bacteria (AOB), and denitrifying bacteria (nirK and nirS). The results showed that CP and DCD obviously inhibited NH4+-N conversion, and NO2--N, and NO3--N accumulation, NBPT slowed down urea hydrolysis and NH4+-N production, and the apparent nitrification rates of soil were in the following order: NBPT > DCD > DCD + NBPT > CP + NBPT > CP. Compared with urea treatment, the peak N2O production rate of inhibitor treatment decreased by 73.30-99.30%, and the production rate of CH4 and CO2 decreased by more than 66.16%. DCD and CP reduced the abundance of AOA and AOB, respectively. Furthermore, NBPT hindered the growth of ammonia-oxidizing microorganisms and nirS-type denitrifying bacteria, and urea and nitrification inhibitors were detrimental to the growth of Ensifer and Sinorhizobium in the nirK community. Nitrification and urease inhibitors can effectively slow down nitrification and greenhouse gas emissions, reduce N loss and improve soil quality by inhibiting the growth of ammonia-oxidizing microorganisms and denitrifying bacteria.

Pyrite and sulfur-coupled autotrophic denitrification system for efficient nitrate and phosphate removal.

The inefficiency of nitrogen removal in pyrite autotrophic denitrification (PAD) and the low efficiency of PO43--P removal in sulfur autotrophic denitrification (SAD) limit their potential for engineering applications. This study examined the use of pyrite and sulfur coupled autotrophic denitrification (PSAD) in batch and column experiments to remove NO3--N and PO43--P from sewage. The effluent concentration of NO3--N was 0.32 ± 0.11 mg/L, with an average Total nitrogen (TN) removal efficiency of 99.14%. The highest PO43--P removal efficiency was 100% on day 18. There was a significant correlation between pH and the efficiency of PO43--P removal. Thiobacillus, Thiomonas and Thermomonas were found to be dominant at the bacterial genus level in PSAD. Additionally, the abundance of Thermomonas in the PSAD was greater than that observed in the SAD reactor. This result indirectly indicates that the PSAD system has more advantages in reducing N2O.

Heterogeneous Regulation of StaphylococcusAureus by Different StaphylococcusEpidermidisagr Types in Atopic Dermatitis.

The skin commensal Staphylococcus epidermidis exhibits a protective role in skin inflammation; however, the exact functions of S. epidermidis and their mechanisms in atopic dermatitis (AD) are not fully understood. Here, whole-genome sequencing was conducted on strains of S. epidermidis isolated from pediatric patients with AD and revealed significant strain-level heterogeneity in functional genes. Specific sequence analysis of S. epidermidis identified four types of accessory gene regulator (agr) according to locus variations in the agr operon, which was consistent with the metagenomic data of the contextual microbiota. The number of S. epidermidisagr type I was slightly decreased among AD isolates, whereas agr type IV was hardly detected in AD isolates. Functional experiments showed that strains of S. epidermidisagr types I and IV, but not types II and III, inhibited the expression of S. aureusagr-mediated virulence factors in vitro, suppressed S. aureus epidermal colonization, and attenuated skin inflammation in a mouse model. The delineation of genome signatures of S. epidermidis at the strain level in AD and the quorum-sensing interference between S. epidermidisagr type IV and S. aureus provide a foundation for the modulation of the skin microbiota and the treatment of AD.