Populus euphratica R2R3-MYB transcription factor RAX2 binds ANN1 promoter to increase cadmium enrichment in Arabidopsis.

The expression of R2R3-MYB transcription factor PeRAX2 increased transiently upon CdCl2 exposure (100 µM, 48 h) in leaves and roots of Populus euphratica. We observed that overexpression of PeRAX2 increased Cd2+ concentration in Arabidopsis root cells and Cd2+ amount in whole plant, which was due to the increased Cd2+ influx into root tips. However, the Cd2+ influx facilitated by PeRAX2 overexpression was substantially reduced by LaCl3 (an inhibitor of Ca2+-channels), suggesting that PeRAX2 could promote the Cd2+ entering through PM Ca2+-permeable channels (CaPCs) in the roots. It is noting that the expression of annexin1 (AtANN1), which mediates the influx of divalent cations through the PM calcium channels, was upregulated by Cd2+ in PeRAX2-transgenic Arabidopsis. Bioinformatic analysis revealed that the AtANN1 promoter (AtANN1-pro) contains four cis-elements for MYB binding. The PeRAX2 interaction with AtANN1-pro was validated by LUC reporter assay, EMSA, and Y1H assay. Our data showed that PeRAX2 binds to the AtANN1 promoter region to regulate gene transcription and that AtANN1 mediates the Cd2+ entry through CaPCs in the PM, leading to a Cd2+ enrichment in transgenic plants. The PeRAX2-stimulated Cd2+ enrichment consequently resulted in high H2O2 production in root cells of transgenic plants. The expression of AtSOD and AtPOD and activities of CAT, SOD, POD increased in the transgenic lines under Cd2+ stress. However, the Cd2+-upregulated expression and activity of antioxidative enzymes were less pronounced in the PeRAX2-overexpressed lines, compared to the wildtype and vector controls. As a result, root length and plant growth were more suppressed by Cd2+ in the transgenic lines. Our data suggest that transcriptional regulation of AtANN1 by PeRAX2 can be utilized to improve Cd2+ enrichment and phytoremediation, although the enriched Cd2+ affected antioxidant defense system and plant growth in the model species.

Genetic variants, haplotype determination, and function of novel alleles of CYP2B6 in a Han Chinese population.

Amino acid variants in protein may result in deleterious effects on enzymatic activity. In this study we investigate the DNA variants on activity of CYP2B6 gene in a Chinese Han population for potential use in precision medicine. All exons in CYP2B6 gene from 1483 Chinese Han adults (Zhejiang province) were sequenced using Sanger sequencing. The effects of nonsynonymous variants on recombinant protein catalytic activity were investigated in vitro with Sf12 system. The haplotype of novel nonsynonymous variants with other single nucleotide variants in the same allele was determined using Nanopore sequencing. Of 38 alleles listed on the Pharmacogene Variation Consortium, we detected 7 previously reported alleles and 18 novel variants, of which 11 nonsynonymous variants showed lower catalytic activity (0.00-0.60) on bupropion compared to CYP2B6*1. Further, these 11 novel star-alleles (CYP2B6*39-49) were assigned by the Pharmacogene Variation Consortium, which may be valuable for pharmacogenetic research and personalized medicine.

Low concentrations of cyantraniliprole negatively affects the development of Spodoptera frugiperda by disruption of ecdysteroid biosynthesis and carbohydrate and lipid metabolism.

In addition to the acute lethal toxicity, insecticides might affect population dynamics of insect pests by inducing life history trait changes under low concentrations, however, the underlying mechanisms remain not well understood. Here we examined systemic impacts on development and reproduction caused by low concentration exposures to cyantraniliprole in the fall armyworm (FAW), Spodoptera frugiperda, and the putative underlying mechanisms were investigated. The results showed that exposure of third-instar larvae to LC10 and LC30 of cyantraniliprole significantly extended larvae duration by 1.46 and 5.41 days, respectively. Treatment with LC30 of cyantraniliprole significantly decreased the pupae weight and pupation rate as well as the longevity, fecundity and egg hatchability of female adults. Consistently, we found that exposure of FAW to LC30 cyantraniliprole downregulated the mRNA expression of four ecdysteroid biosynthesis genes including SfNobo, SfShd, SfSpo and SfDib and one ecdysone response gene SfE75 in the larvae as well as the gene encoding vitellogenin (SfVg) in the female adults. We also found that treatment with LC30 of cyantraniliprole significantly decreased the whole body levels of glucose, trehalose, glycogen and triglyceride in the larvae. Our results indicate that low concentration of cyantraniliprole inhibited FAW development by disruption of ecdysteroid biosynthesis as well as carbohydrate and lipid metabolism, which have applied implications for the control of FAW.

Development and validation of a pyroptosis-related prognostic signature associated with osteosarcoma metastasis and immune infiltration.

Pyroptosis is a programmed cell death, which has garnered increasing attention because it relates to the immune and therapy response. However, few studies focus on the application of pyroptosis-related genes (PRGs) in predicting osteosarcoma (OS) patients' prognoses. In this study, the gene expression and clinical information of OS patients were downloaded from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database. Based on these PRGs and unsupervised clustering analysis, all OS samples can be classified into 2 clusters. The 8 key differential expressions for PRGs (LAG3, ITGAM, CCL2, TLR4, IL2RA, PTPRC, FCGR2B, and CD5) were established through the univariate Cox regression and utilized to calculate the risk score of all samples. According to the 8-gene signature, OS samples can be divided into high and low-risk groups and correlation analysis can be performed using immune cell infiltration and immune checkpoints. Finally, we developed a nomogram to improve the PRG-predictive model in clinical application. We verified the predictive performance using receiver operating characteristic (ROC) and calibration curves. There were significant differences in survival, immune cell infiltration and immune checkpoints between the low and high-risk groups. A nomogram was developed with clinical indicators and the risk scores were effective in predicting the prognosis of patients with OS. In this study, a prognostic model was constructed based on 8 PRGs were proved to be independent prognostic factors of OS and associated with tumor immune microenvironment. These 8 prognostic genes were involved in OS development and may serve as new targets for developing therapeutic drugs.

Populus euphratica PeNADP-ME interacts with PePLDδ to mediate sodium and ROS homeostasis under salinity stress.

Populus euphratica phospholipase Dδ (PePLDδ) is transcriptionally regulated and mediates reactive oxygen species (ROS) and ion homeostasis under saline conditions. The purpose of this study is to explore the post-transcriptional regulation of PePLDδ in response to salt environment. P. euphratica PePLDδ was shown to interact with the NADP-dependent malic enzyme (NADP-ME) by screening the yeast two-hybrid libraries. The transcription level of PeNADP-ME increased upon salt exposure to NaCl (200 mM) in leaves and roots of P. euphratica. PeNADP-ME had a similar subcellular location with PePLDδ in the cytoplasm, and the interaction between PeNADP-ME and PePLDδ was further verified by GST pull-down and yeast two-hybrid. To clarify whether PeNADP-ME interacts with PePLDδ to enhance salt tolerance, PePLDδ and PeNADP-ME were overexpressed singly or doubly in Arabidopsis thaliana. Dual overexpression of PeNADP-ME and PePLDδ resulted in an even more pronounced improvement in salt tolerance compared with single transformants overexpressing PeNADP-ME or PePLDδ alone. Greater Na+ limitation and Na+ efflux in roots were observed in doubly overexpressed plants compared with singly overexpressed plants with PeNADP-ME or PePLDδ. Furthermore, NaCl stimulation of SOD, APX, and POD activity and transcription were more remarkable in the doubly overexpressed plants. It is noteworthy that the enzymic activity of NADP-ME and PLD, and total phosphatidic acid (PA) concentrations were significantly higher in the double-overexpressed plants than in the single transformants. We conclude that PeNADP-ME interacts with PePLDδ in Arabidopsis to promote PLD-derived PA signaling, conferring Na+ extrusion and ROS scavenging under salt stress.

Axillary vein as an alternative venous access site for VV-ECMO cannulation: a case report.

BACKGROUND: Ultrasound-guided percutaneous axillary vein cannulation can reduce cannulation failure and mechanical complications, is as safe and effective as internal jugular vein cannulation, and is superior to subclavian vein cannulation using landmark technique. As far, reports of venovenous extracorporeal membrane oxygenation (VV-ECMO) with percutaneous axillary vein cannulation are rare. CASE PRESENTATION: A 64-year-old man presenting with dyspnea and chest tightness after aspirating sewage was admitted to the emergency department. Computed tomography (CT) showed diffuse exudation of both lungs and arterial blood gas analysis showed an oxygenation index of 86. He was diagnosed with aspiration pneumonia-induced acute respiratory distress syndrome (ARDS) and intubated for deteriorated oxygenation. Despite the combination therapy of protective mechanical ventilation and prone position, the patient's oxygenation deteriorated further, accompanied with multiple organ dysfunction syndrome, which indicated the requirement of support with VV-ECMO. However, vascular ultrasound detected multiple thrombus within bilateral internal jugular veins. As an alternative, right axillary vein was chosen as the access site of return cannula. Subsequently, femoral-axillary VV-ECMO was successfully implemented under the ultrasound guidance, and the patient's oxygenation was significantly improved. Unfortunately, the patient died of hyperkalemia-induced ventricular fibrillation after 36 h of VV-ECMO running. Despite the poor prognosis, the blood flow during ECMO run was stable, and we observed no bleeding complication, vascular injury, or venous return disorder. CONCLUSIONS: Axillary vein is a feasible alternative access site of return cannula for VV-ECMO if internal jugular vein access were unavailable.

Functional Characterization and Putative Regulatory Mechanism of an RNAi Efficiency-Related Nuclease (REase) in the Fall Armyworm, Spodoptera frugiperda.

The lepidopteran-specific RNAi efficiency-related nuclease (REase) has been shown to contribute to double-strand RNA (dsRNA) degradation in several lepidopteran insects. However, little is known about its regulatory mechanism. In this study, we identified and characterized SfREase in Spodoptera frugiperda. The exposure of the third-instar larvae to dsEGFP and high temperature led to the upregulation of SfREase, whereas starvation treatment resulted in the downregulation of SfREase. Further experiments revealed that dsRNA degraded more slowly in the hemolymph or midgut fluid extracted from dsSfREase-injected or dsSfREase-ingested larvae compared with those from dsEGFP-treated larvae, and the recombinant SfREase degraded dsRNA in a concentration-dependent manner. Additionally, the knockdown of SfREase improved RNAi efficiency. Finally, both RNAi and dual-luciferase reporter assay in Sf9 cells revealed that SfREase is negatively regulated by FOXO. These data provide insights into the function and regulatory mechanism of REase and have applied implications for the development of an RNAi-based control strategy of S. frugiperda.

Photocatalytic Cyclization Cascades by Radical Relay toward Pyrrolo[1,2-a]indoles: Synthesis, Mechanism, and Application.

A photocatalytic annulation cascade of unactivated N-alkene-linked indoles with Langlois' reagent by a radical relay is developed at room temperature under blue LED irradiation. The reaction afforded a series of tri/difluoromethylated pyrrolo[1,2-a]indoles in moderate to good yields. The DFT study suggests that the reaction is ascribed to a rhodamine 6G-induced cyclization cascade involving vinyl addition-radical relay and hydrogen-atom-abstraction (HAA) processes, and interestingly, pyrrolo[1,2-a]indoles are applied as fluorescent dyes into the fluorescence spectrum and live-cell imaging. This paper represents an initial example on photocatalytic cyclization cascades by radical relay and the HAA process.

Effect of NaCl on ammonium and nitrate uptake and transport in salt-tolerant and salt-sensitive poplars.

Nitrogen (N) plays an important role in mitigating salt stress in tree species. We investigate the genotypic differences in the uptake of ammonium (NH4+) and nitrate (NO3-) and the importance for salt tolerance in two contrasting poplars, salt-tolerant Populus euphratica Oliv. and salt-sensitive P. simonii × (P. pyramidalis ×Salix matsudana) (P. popularis cv. 35-44, P. popularis). Total N content, growth and photosynthesis were significantly reduced in P. popularis after 7 days of exposure to NaCl (100 mM) supplied with 1 mM NH4+ and 1 mM NO3-, while the salt effects were not pronounced in P. euphratica. The 15NH4+ trace and root flux profiles showed that salt-stressed poplars retained ammonium uptake, which was related to the upregulation of ammonium transporters (AMTs) in roots, as two of the four AMTs tested significantly increased in salt-stressed P. euphratica (i.e., AMT1.2, 2.1) and P. popularis (i.e., AMT1.1, 1.6). It should be noted that P. euphratica differs from salt-sensitive poplar in the maintenance of NO3- under salinity. 15NO3- tracing and root flux profiles showed that P. euphratica maintained nitrate uptake and transport, while the capacity to uptake NO3- was limited in salt-sensitive P. popularis. Salt increased the transcription of nitrate transporters (NRTs), NRT1.1, 1.2, 2.4, 3.1, in P. euphratica, while P. popularis showed a decrease in the transcripts of NRT1.1, 2.4, 3.1 after 7 days of salt stress. Furthermore, salt-stimulated transcription of plasmalemma H+-ATPases (HAs), HA2, HA4 and HA11 contributed to H+-pump activation and NO3- uptake in P. euphratica. However, salt stimulation of HAs was less pronounced in P. popularis, where a decrease in HA2 transcripts was observed in the stressed roots. We conclude that the salinity-decreased transcripts of NRTs and HAs reduced the ability to uptake NO3- in P. popularis, resulting in limited nitrogen supply. In comparison, P. euphratica maintains NH4+ and NO3- supply, mitigating the negative effects of salt stress.

Dynamic arterial elastance as a predictor of arterial pressure response to norepinephrine weaning in mechanically ventilated patients with vasoplegic syndrome-a systematic review and meta-analysis.

Introduction: During the de-escalation phase of circulatory shock, norepinephrine weaning may induce diverse arterial pressure responses in patients with different vasomotor tones. Dynamic arterial elastance (Eadyn) has been extensively studied to predict the arterial pressure response to interventions. We conducted this meta-analysis to systematically assess the predictive performance of Eadyn for the mean arterial pressure (MAP) response to norepinephrine weaning in mechanically ventilated patients with vasoplegic syndrome. Materials and methods: A systematic literature search was conducted on May 29, 2023 (updated on January 21, 2024), to identify relevant studies from electronic databases. The area under the hierarchical summary receiver operating characteristic curve (AUHSROC) was estimated as the primary measure of diagnostic accuracy because of the varied thresholds reported. Additionally, we observed the distribution of the cutoff values of Eadyn, while computing the optimal value and its corresponding 95% confidential interval (CI). Results: A total of 5 prospective studies met eligibility, comprising 183 participants, of whom 67 (37%) were MAP responders. Eadyn possessed an excellent ability to predict the MAP response to norepinephrine weaning in patients with vasoplegic syndrome, with an AUHSROC of 0.93 (95% CI: 0.91-0.95), a pooled sensitivity of 0.94 (95% CI: 0.85-0.98), a pooled specificity of 0.73 (95% CI: 0.65-0.81), and a pooled diagnostic odds ratio of 32.4 (95% CI: 11.7-89.9). The cutoff values of Eadyn presented a nearly conically symmetrical distribution; the mean and median cutoff values were 0.89 (95% CI: 0.80-0.98) and 0.90 (95% CI: not estimable), respectively. Conclusions: This meta-analysis with limited evidences demonstrates that Eadyn may be a reliable predictor of the MAP response to norepinephrine weaning in mechanically ventilated patients with vasoplegic syndrome. Systematic Review Registration: PROSPERO CRD42023430362.

Populus euphratica GRP2 Interacts with Target mRNAs to Negatively Regulate Salt Tolerance by Interfering with Photosynthesis, Na+, and ROS Homeostasis.

The transcription of glycine-rich RNA-binding protein 2 (PeGRP2) transiently increased in the roots and shoots of Populus euphratica (a salt-resistant poplar) upon initial salt exposure and tended to decrease after long-term NaCl stress (100 mM, 12 days). PeGRP2 overexpression in the hybrid Populus tremula × P. alba '717-1B4' (P. × canescens) increased its salt sensitivity, which was reflected in the plant's growth and photosynthesis. PeGRP2 contains a conserved RNA recognition motif domain at the N-terminus, and RNA affinity purification (RAP) sequencing was developed to enrich the target mRNAs that physically interacted with PeGRP2 in P. × canescens. RAP sequencing combined with RT-qPCR revealed that NaCl decreased the transcripts of PeGRP2-interacting mRNAs encoding photosynthetic proteins, antioxidative enzymes, ATPases, and Na+/H+ antiporters in this transgenic poplar. Specifically, PeGRP2 negatively affected the stability of the target mRNAs encoding the photosynthetic proteins PETC and RBCMT; antioxidant enzymes SOD[Mn], CDSP32, and CYB1-2; ATPases AHA11, ACA8, and ACA9; and the Na+/H+ antiporter NHA1. This resulted in (i) a greater reduction in Fv/Fm, YII, ETR, and Pn; (ii) less pronounced activation of antioxidative enzymes; and (iii) a reduced ability to maintain Na+ homeostasis in the transgenic poplars during long-term salt stress, leading to their lowered ability to tolerate salinity stress.

Exploring gut-lung axis crosstalk in SARS-CoV-2 infection: Insights from a hACE2 mouse model.

Based on the forefront of clinical research, there is a growing recognition that the gut microbiota, which plays a pivotal role in shaping both the innate and adaptive immune systems, may significantly contribute to the pathogenesis of coronavirus disease 2019 (COVID-19). Although an association between altered gut microbiota and COVID-19 pathogenesis has been established, the causative mechanisms remain incompletely understood. Additionally, the validation of the precise functional alterations within the gut microbiota relevant to COVID-19 pathogenesis has been limited by a scarcity of suitable animal experimental models. In the present investigation, we employed a newly developed humanized ACE2 knock-in (hACE2-KI) mouse model, capable of recapitulating critical aspects of pulmonary and intestinal infection, to explore the modifications in the gut microbiota following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Examination of fecal samples using 16S rRNA gene profiling unveiled a notable reduction in species richness and conspicuous alterations in microbiota composition at 6 days postinfection (dpi). These alterations were primarily characterized by a decline in beneficial bacterial species and an escalation in certain opportunistic pathogens. Moreover, our analysis entailed a correlation study between the gut microbiota and plasma cytokine concentrations, revealing the potential involvement of the Lachnospiraceae_NK4A136_group and unclassified_f_Lachnospiraceae genera in attenuating hyperinflammatory responses triggered by the infection. Furthermore, integration of gut microbiota data with RNA-seq analysis results suggested that the increased presence of Staphylococcus in fecal samples may signify the potential for bacterial coinfection in lung tissues via gut translocation. In summary, our hACE2-KI mouse model effectively recapitulated the observed alterations in the gut microbiota during SARS-CoV-2 infection. This model presents a valuable tool for elucidating gut microbiota-targeted strategies aimed at mitigating COVID-19.

Significance of Oxidative Stress in the Diagnosis and Subtype Classification of Intervertebral Disc Degeneration.

Intervertebral disc degeneration (IVDD) is a common illness of aging, and its pathophysiological process is mainly manifested by cell aging and apoptosis, an imbalance in the production and catabolism of extracellular matrix, and an inflammatory response. Oxidative stress (OS) is an imbalance that decreases the body's intrinsic antioxidant defense system and/or raises the formation of reactive oxygen species and performs multiple biological functions in the body. However, our current knowledge of the effect of OS on the progression and treatment of IVDD is still extremely limited. In this study, we obtained 35 DEGs by differential expression analysis of 437 OS-related genes (OSRGs) between IVDD patients and healthy individuals from GSE124272 and GSE150408. Then, we identified six hub OSRGs (ATP7A, MELK, NCF1, NOX1, RHOB, and SP1) from 35 DEGs, and the high accuracy of these hub genes was confirmed by constructing ROC curves. In addition, to forecast the risk of IVDD patients, we developed a nomogram. We obtained two OSRG clusters (clusters A and B) by consensus clustering based on the six hub genes. Then, 3147 DEGs were obtained by differential expression analysis in the two clusters, and all samples were further divided into two gene clusters (A and B). We investigated differences in immune cell infiltration levels between different clusters and found that most immune cells had higher infiltration levels in OSRG cluster B or gene cluster B. In conclusion, OS is important in the formation and progression of IVDD, and we believe that our work will help guide future research on OS in IVDD.

"We are in the forgotten corner!" a qualitative study of experiences and challenges among Chinese older women at the onset of acute myocardial infarction.

Background: Acute myocardial infarction (AMI) is a common and serious cardiovascular disease (CVD) that is one of the leading causes of death among women globally and in China. However, there are sex-associated differences and inequalities in the detection and management of AMI, especially in older people. There is little research demonstrating how challenges and barriers affect older women's help-seeking behavior and health-related procedures in China. Purpose: The objective of this study was to explore the experiences of older women with AMI, focusing on their perception, challenges, and coping strategies at the onset of AMI in Wuhan, China. Methods: This study utilized a qualitative research design approach and conducted semi-structured, in-depth, and audio-recorded interviews with 18 women aged 65-84 years, purposively selected from two tertiary hospitals in Wuhan City from November 2021 to April 2022. Results: Interpretative Phenomenological Analysis (IPA) was used in this study to analyze the data on 18 participants and three major themes were generated: disease perception disorder, negative coping strategies, and barriers due to social-environmental contexts. Conclusion: To reduce older women's delay in seeking help, healthcare professionals should provide public health education that emphasizes sex-related disparities, and age-specific knowledge-attitude aspects to high-risk groups. Policy-based and health administration recommendations, including e-health information support, access to care, and social-environmental factors, should be highlighted to promote women's health behavior.

Compared to antibiotic, feeding peony byproducts can improve growth performance, rumen fermentation, slaughter parameters, and meat quality of lambs.

Our objective was to determine effects of feeding lamb's peony byproducts, including stem and leaves (PSL), root (PR), and seeds meal (PSM), on growth, rumen fermentation, slaughter parameters, and meat quality. Sixty-four lambs (14.0 ± 2.1 kg) were allocated into eight treatments based on BW: no additives (CON), 0.15% aureomycin (CONA), low/high levels of PSL (5%/10% PSL replaced 5%/10% Chinese hay), PR (basal diet with 0.5%/1.0% PR), PSM (5%/10% PSM replaced 5%/10% soybean meal). Growth, digestibility, and rumen fermentation had dose responses whereas slaughter parameters, meat quality, or amino acids indexes were not. Peony byproducts increased DMI (p < 0.001) compared to CON, but higher levels were more advantageous (p = 0.003). However, low levels of peony byproducts decreased the NH3 -N concentration, but increased total volatile fatty acids mole percent more than high levels of that (p < 0.001). All peony byproducts increased dressing percentage (p < 0.05), increased pH and tenderness than CON (p < 0.05). In addition, PSL and PSM improved amino acid profiles of meat compared to CON, and were even better than CONA (p < 0.05). Therefore, peony byproducts not only improved animal growth but also reduced the frequency of antibiotic use in animal feeding.

Mortality and Cumulative Kidney Score are Associated with Transient and Persistent Acute Kidney Injury in Septic Patients: A Retrospective Study Based on MIMIC-IV.

BACKGROUND: Acute kidney injury (AKI) is frequently caused by sepsis. Recently, the Acute Disease Quality Initiative (ADQI) workgroup further classified AKI as transient or persistent. Oliguria and increased serum creatinine represent two different kinds of renal impairment. The aim of the study was to assess mortality and cumulative AKI score associated with transient and persistent AKI in septic patients. METHODS: Septic patients were stratified according to the presence and AKI development (considered persistent when remaining >48 h) were included. An adjusted logistic regression model was used to determine hospital mortality. In addition, we calculated an AKI score by combining both Kidney Disease: Improving Global Outcomes (KDIGO) criteria of urine output and creatinine AKI stages. The relationship between the cumulative AKI score and persistent AKI was further examined using the logistic regression model and receiver operating characteristic (ROC) curve analysis. RESULTS: 12928 septic patients were enrolled in the study. AKI occurred in 73.7% of septic patients, in 39.5% was transient and in 60.5% was persistent. Patients with persistent AKI had higher severity scores and more severe renal dysfunction upon admission. Persistent AKI, but not transient AKI, was associated with increased intensive care units (ICUs) and hospital mortality. Then we found that the cumulative AKI score was associated with an increased risk of persistent AKI. This association was consistent across three original KDIGO severity stages and subgroup analyses. CONCLUSIONS: It was found that persistent AKI was independently associated with mortality in septic patients. Furthermore, serum creatinine and urine output criteria had cumulative effects on KDIGO AKI staging and provided more information about the relationship between AKI and outcomes.

Prophylactic noninvasive respiratory support in the immediate postoperative period after cardiac surgery - a systematic review and network meta-analysis.

BACKGROUND: Noninvasive respiratory support has been increasingly applied in the immediate postoperative period to prevent postoperative pulmonary complications (PPCs). However, the optimal approach remains uncertain. We sought to evaluate the comparative effectiveness of various noninvasive respiratory strategies used in the immediate postoperative period after cardiac surgery. METHODS: We conducted a frequentist random-effect network meta-analysis (NMA) of randomized controlled trials (RCTs) comparing the prophylactic use of noninvasive ventilation (NIV), continuous positive airway pressure (CPAP), high flow nasal cannula (HFNC), or postoperative usual care (PUC) in the immediate postoperative period after cardiac surgery. Databases were systematically searched through September 28, 2022. Study selection, data extraction, and quality assessment were performed in duplicate. The primary outcome was the incidence of PPCs. RESULTS: Sixteen RCTs enrolling 3011 patients were included. Compared with PUC, NIV significantly reduced the incidence of PPCs [relative risk (RR) 0.67, 95% confidence interval (CI): 0.49 to 0.93; absolute risk reduction (ARR) 7.6%, 95% CI: 1.6-11.8%; low certainty] and the incidence of atelectasis (RR 0.65, 95% CI: 0.45 to 0.93; ARR 19.3%, 95% CI: 3.9-30.4%; moderate certainty); however, prophylactic NIV was not associated with a decreased reintubation rate (RR 0.82, 95% CI: 0.29 to 2.34; low certainty) or reduced short-term mortality (RR 0.64, 95% CI: 0.16 to 2.52; very low certainty). As compared to PUC, the preventive use of CPAP (RR 0.85, 95% CI: 0.60 to 1.20; very low certainty) or HFNC (RR 0.74, 95% CI: 0.46 to 1.20; low certainty) had no significant beneficial effect on the incidence of PPCs, despite exhibiting a downward trend. Based on the surface under the cumulative ranking curve, the highest-ranked treatment for reducing the incidence of PPCs was NIV (83.0%), followed by HFNC (62.5%), CPAP (44.3%), and PUC (10.2%). CONCLUSIONS: Current evidence suggest that the prophylactic use of NIV in the immediate postoperative period is probably the most effective noninvasive respiratory approach to prevent PPCs in patients undergoing cardiac surgery. Given the overall low certainty of the evidence, further high-quality research is warranted to better understand the relative benefits of each noninvasive ventilatory support. CLINICAL TRIAL REGISTRATION: PROSPERO, https://www.crd.york.ac.uk/prospero/ , registry number: CRD42022303904.

A novel hACE2 knock-in mouse model recapitulates pulmonary and intestinal SARS-CoV-2 infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission is responsible for the coronavirus disease 2019 (COVID-19) pandemic. SARS-CoV-2 uses the angiotensin-converting enzyme 2 (ACE2) receptor to enter the host, and the gastrointestinal tract is a potential infection site as this receptor is expressed on it. Multiple studies have indicated that an increasing number of COVID-19 patients presented with gastrointestinal symptoms that are highly associated with disease severity. Moreover, emerging evidence has demonstrated that alterations in the gut immune microenvironment induced by intestinal SARS-CoV-2 infection can regulate respiratory symptoms. Therefore, targeting the intestines may be a candidate therapeutic strategy in patients with COVID-19; however, no mouse model can serve as an appropriate infection model for the development of fatal pneumonia while mimicking intestinal infection. In this study, a novel human ACE2 knock-in (KI) mouse model (or hACE2-KI) was systemically compared with the popular K18-hACE2 mice; it showed differences in the distribution of lung and intestinal infections and pathophysiological characteristics. These newly generated hACE2-KI mice were susceptible to intranasal infection with SARS-CoV-2, and not only developed mild to severe lung injury, but also acquired intestinal infection. Consequently, this model can be a useful tool for studying intestinal SARS-CoV-2 infection and developing effective therapeutic strategies.