Vascular endothelial glycocalyx shedding in ventilator-induced lung injury in rats.

Endothelial permeability deterioration is involved in ventilator-induced lung injury (VILI). The integrality of vascular endothelial glycocalyx (EG) is closely associated with endothelial permeability. The hypothesis was that vascular EG shedding participates in VILI through promoting endothelial permeability. In the present study, male Sprague-Dawley (SD) rats were ventilated with high tidal volume (VT =40 ml/kg) or low tidal volume (VT =8 ml/kg) to investigate the effects of different tidal volume and ventilation durations on EG in vivo. We report disruption of EG during the period of high tidal volume ventilation characterized by increased glycocalyx structural components (such as syndecan-1, heparan sulfate, hyaluronan) in the plasma and decreased the expression of syndecan-1 in the lung tissues. Mechanistically, the disruption of EG was associated with increased proinflammatory cytokines and matrix metalloproteinase in the lung tissues. Collectively, these results demonstrate that the degradation of EG is involved in the occurrence and development of VILI in rats, and the inflammatory mechanism mediated by activation of the NF-κB signaling pathway may be partly responsible for the degradation of EG in VILI in rats. This study enhances our understanding of the pathophysiological processes underlying VILI, shedding light on potential therapeutic targets to mitigate VILI.

Elder mistreatment and cognitive functioning among Chinese older adults in the U.S.

Elder mistreatment disproportionately affects racial and ethnic minority older adults, particularly Chinese older adults in the U.S. who face increased risks due to cultural disparities, intergenerational conflicts, and socioeconomic disparities. This study investigated the longitudinal association of elder mistreatment with cognitive functioning among Chinese older adults in the Greater Chicago area (N = 2,811). Self-reported elder mistreatment and cognitive performance were assessed across four waves of the study. Latent growth curve modeling analysis showed that respondents reporting previous mistreatment instances at baseline exhibited better initial functioning status (B = 0.07, p < .05); however, those reporting mistreatment incidents at three follow-ups showed a faster cognitive decline compared to those without such reports (B = -0.04, p < .05). Recent and potentially cumulative experiences of elder mistreatment have a negative effect on cognitive decline. Sociocultural contexts need to be considered when addressing elder mistreatment issues within the Chinese minority community.

Smoke exposure associated with higher urinary benzene biomarker muconic acid (MUCA) in Golestan Cohort Study participants.

Background. Benzene is a known human carcinogen. Human exposure to benzene can be assessed by measuring trans, trans-muconic acid (MUCA) in urine. Golestan Province in northeastern Iran has been reported to have high incidence of esophageal cancer linked to the use of tobacco products. This manuscript evaluates the urinary MUCA concentrations among the participants of the Golestan Cohort Study (GCS).Methods. We analyzed MUCA concentration in 177 GCS participants' urine samples and performed nonparametric pairwise multiple comparisons to determine statistically significant difference among six different product use groups. Mixed effects model was fitted on 22 participants who exclusively smoked cigarette and 51 participants who were classified as nonusers. The urinary MUCA data were collected at the baseline and approximately five years later, and intraclass correlation coefficient (ICC) was calculated from the model.Results. Compared with nonusers, tobacco smoking was associated with higher urinary MUCA concentrations. Based on the nonparametric test of pairwise multiple comparisons, MUCA concentrations among participants who smoked combusted tobacco products were statistically significantly higher compared to nonusers. Urinary MUCA collected five years apart from the same individuals showed moderate reliability (ICC = 0.41), which was expected given the relatively short half-life (∼6 h) of MUCA.Conclusion. Our study revealed that tobacco smoke was positively associated with increased levels of urinary MUCA concentration, indicating that it is a significant source of benzene exposure among GCS participants.

Effect of perioperative goal-directed fluid therapy on postoperative complications after thoracic surgery with one-lung ventilation: a systematic review and meta-analysis.

BACKGROUND: An understanding of the impact of goal-directed fluid therapy (GDFT) on the outcomes of patients undergoing one-lung ventilation (OLV) for thoracic surgery remains incomplete and controversial. This meta-analysis aimed to assess the effect of GDFT compared to other fluid therapy strategies on the incidence of postoperative complications in patients with OLV. METHODS: The Embase, Cochrane Library, Web of Science, and MEDLINE via PubMed databases were searched from their inception to November 30, 2022. Forest plots were constructed to present the results of the meta-analysis. The quality of the included studies was evaluated using the Cochrane Collaboration tool and Risk Of Bias In Non-Randomized Study of Interventions (ROBINS-I). The primary outcome was the incidence of postoperative complications. Secondary outcomes were the length of hospital stay, PaO2/FiO2 ratio, total fluid infusion, inflammatory factors (TNF-α, IL-6), and postoperative bowel function recovery time. RESULTS: A total of 1318 patients from 11 studies were included in this review. The GDFT group had a lower incidence of postoperative complications [odds ratio (OR), 0.47; 95% confidence interval (95% CI), 0.29-0.75; P = 0.002; I 2, 67%], postoperative pulmonary complications (OR 0.48, 95% CI 0.27-0.83; P = 0.009), and postoperative anastomotic leakage (OR 0.51, 95% CI 0.27-0.97; P = 0.04). The GDFT strategy reduces total fluid infusion. CONCLUSIONS: GDFT is associated with lower postoperative complications and better survival outcomes after thoracic surgery for OLV.

Amplification and Preparation of Cellular O-Glycomes for Functional Glycomics.

Mucin-type O-glycans play key roles in many cellular processes, and they are often altered in human diseases. A major challenge in studying the role of O-glycans through functional O-glycomics is the absence of a complete repertoire of the glycans that comprise the human O-glycome. Here we describe a cellular O-glycome preparation strategy, Preparative Cellular O-Glycome Reporter/Amplification (pCORA), that introduces 4-N3-Bn-GalNAc(Ac)3 as a novel precursor in large-scale cell cultures to generate usable amounts of O-glycans as a potential O-glycome factory. Cultured human non-small cell lung cancer (NSCLC) A549 cells take up the precursor, which is extended by cellular glycosyltransferases to produce 4-N3-Bn-α-O-glycans that are secreted into the culture medium. The O-glycan derivatives can be clicked with a fluorescent bifunctional tag that allows multidimensional HPLC purification and production of a tagged glycan library, representing the O-glycome of the corresponding cells. We obtained ∼5% conversion of precursor to O-glycans and purified a tagged O-glycan library of over 100 O-glycan derivatives, many of which were present in >100 nmol amounts and were sequenced by sequential MS fragmentation (MSn). These O-glycans were successfully printed onto epoxy glass slides as an O-glycome shotgun microarray. We used this novel array to explore binding activity of serum IgM in healthy persons and NSCLC patients at different cancer stages. This novel strategy provides access to complex O-glycans in significant quantities and may offer a new route to discovery of potential diagnostic disease biomarkers.

Preparative scale purification of natural glycans by closed-loop recycle HPLC.

While glycoscience has become well recognized as an indispensable area in biomedical research, studies on the function of individual glycans remains a great challenge due to the lack of tools and methods. One of the greatest impediments to progress in this area is the lack of biomedically relevant complex glycans in sufficient quantity and purity for structural and functional analysis. Despite recent advances in chemoenzymatic synthesis of complex glycans, generating significant amounts of pure glycans is limited to laboratories with specialized expertise. We have previously reported the oxidative release of natural glycans (ORNG) using household bleach, which provides large quantities of biologically relevant glycans that can be a source of glycans in quantities (>mg scale) suitable for functional studies. However, the preparative scale separation of complicated glycan mixtures has not been studied due largely to the fact that gram quantities of starting glycans have not been available until now. Here we report the adoption of closed-loop, recycle HPLC to resolve closely related glycan structures, including complex glycan isomers at preparative scale (10-100 mg).

Next-Generation Glycan Microarray Enabled by DNA-Coded Glycan Library and Next-Generation Sequencing Technology.

Interactions of glycans with proteins, cells, and microorganisms play important roles in cell-cell adhesion and host-pathogen interaction. Glycan microarray technology, in which multiple glycan structures are immobilized on a single glass slide and interrogated with glycan-binding proteins (GBPs), has become an indispensable tool in the study of protein-glycan interactions. Despite its great success, the current format of the glycan microarray requires expensive, specialized instrumentation and labor-intensive assay and image processing procedures, which limit automation and possibilities for high-throughput analyses. Furthermore, the current microarray is not suitable for assaying interaction with intact cells due to their large size compared to the two-dimensional microarray surface. To address these limitations, we developed the next-generation glycan microarray (NGGM) based on artificial DNA coding of glycan structures. In this novel approach, a glycan library is presented as a mixture of glycans and glycoconjugates, each of which is coded with a unique oligonucleotide sequence (code). The glycan mixture is interrogated by GBPs followed by the separation of unbound coded glycans. The DNA sequences that identify individual bound glycans are quantitatively sequenced (decoded) by powerful next-generation sequencing (NGS) technology, and copied numbers of the DNA codes represent relative binding specificities of corresponding glycan structures to GBPs. We demonstrate that NGGM generates glycan-GBP binding data that are consistent with that generated in a slide-based glycan microarray. More importantly, the solution phase binding assay is directly applicable to identifying glycan binding to intact cells, which is often challenging using glass slide-based glycan microarrays.

A study on the differences in the flocculation of dredged slurries and the influencing mechanisms.

In the water treatment process of natural water bodies, a large amount of dredged slurry with high water content is generated and required for treatment. The coagulation-flocculation method can improve the efficiency of separation, and a suitable scheme is of great significance. It is unclear whether there is a significant difference in flocculation and separation of dredged slurries from different sources and which constituents dominate this process. Facing these problems, the tests were conducted for dredged sediments from 10 different sources, including rivers, lake, and ocean. Under the same flocculation conditions, the difference in the increment of particle size d10, the specific resistance of filtration, and the suspended solids (SS) of the supernatant after sedimentation are 0-4.6 times, 0-2.4 orders of magnitude, and 0-4 orders of magnitude, respectively. It was found that the main constituents in the dredged slurries, such as clay minerals, fulvic acid and humic acid, impact on flocculation and separation effects by affecting the zeta potential of the particles. However, there is no single constituent in the dredged slurry which dominates the flocculation and separation effect. When these constituents are incorporated, the zeta potential exhibited in the slurry determines the difference in flocculation and separation effects.

Anthranilic Acid as a Versatile Fluorescent Tag and Linker for Functional Glycomics.

The advancement of glycoscience is critically dependent on the access to a large number of glycans for their functional study. Naturally occurring glycans are considered a viable source for diverse and biologically relevant glycan libraries. A mixture of free reducing glycans released from natural sources can be fluorescently tagged and separated by chromatography to produce a natural glycan library. Anthranilic acid (AA) has been widely used to fluorescently tag reducing glycans for HPLC or LC/MS analysis. However, AA conjugated glycans are not efficiently immobilized on microarray slides due to the lack of a primary alkylamine functional group. In this study, we have developed simple and efficient chemistry for bioconjugation and further functionalization of glycan-AA conjugates. This new approach enables quick preparation of glycan microarrays and neoglycoproteins from glycan-AA conjugates, which can be separated by weak anion exchange (WAX) and C18 reversed-phase HPLC.

Impacts of Acculturation on Depressive Symptoms and Activities of Daily Living of U.S. Older Chinese Immigrants.

BACKGROUND AND OBJECTIVES: Acculturation is a critical aspect of social experience for immigrants, including Asian immigrants. Existing literature has shown mixed findings on the health impacts of acculturation and largely relied on cross-sectional studies, preventing drawing definitive conclusions. This study aimed to examine the long-term effects of acculturation on depressive symptoms and activities of daily living (ADL) limitations in a large sample of older Chinese immigrants in the United States. RESEARCH DESIGN AND METHODS: Data were drawn from 2,811 older Chinese immigrants from the Population Study of Chinese Elderly in Chicago. Acculturation was assessed at baseline, and questionnaires on depressive symptoms and ADL limitations were completed at 4 assessments. RESULTS: Overall, results showed that acculturation was not associated with depressive symptoms at baseline but was associated with a faster decline in depressive symptoms over time. No associations were found between acculturation and ADL limitations. Stratified analyses showed that the significant relationship between acculturation and a faster decline in depressive symptoms was only evident among female participants. Also, acculturation was associated with a lower risk of reporting ADL limitations at baseline in female participants but a higher risk of reporting ADL limitations in male participants. DISCUSSION AND IMPLICATIONS: This study indicates the long-term benefits of acculturation on mental health among older Chinese immigrants in the United States, particularly among females. Initiatives supporting the acculturation process need to consider sex disparities and individual preferences, aiming to foster sustained benefits for healthy aging in this population.

Sleep quality and cognitive functioning among Chinese older adults living in the US: A mixed-effects model analysis.

Background: Racial and ethnic disparities in sleep quality and cognitive health are increasingly recognized, yet little is understood about their associations among Chinese older adults living in the United States. This study aims to examine the relationships between sleep parameters and cognitive functioning in this population, utilizing data from the Population Study of Chinese Elderly in Chicago (PINE). Methods: This observational study utilized a two-wave panel design as part of the PINE, including 2,228 participants aged 65 years or older, self-identified as Chinese, who completed interviews at two time points. Cognitive functioning was assessed using a battery of tests on perceptual speed, episodic memory, working memory, and mental status. Sleep quality was assessed using Pittsburgh sleep quality index (PSQI) with four aspects: subjective sleep quality, sleep latency, sleep efficiency, and sleep duration at night. Insomnia was assessed using four items from the Women's Health Initiative Insomnia Rating Scale. Mixed-effects regression models were estimated to assess the predictive effects of sleep parameters on baseline cognitive functioning and the rate of cognitive change over time. Results: Significant negative associations were observed between poor sleep quality and baseline cognitive functioning across various domains, although these initial negative associations diminished over time. More insomnia problems were related to poorer perceptual speed and episodic memory. Long sleep latency, or a long time to sleep onset, was associated with worse functioning across all domains except mental status. Sleep efficiency showed inconsistent associations with various cognitive domains, while sleep duration showed no significant relation to any domains. Conclusions: These findings suggest that poor sleep quality indicators serve as early markers of cognitive impairments. Hence, targeted interventions aimed at improving sleep quality could potentially enhance cognitive health outcomes.

Social Disconnectedness, Perceived Loneliness, and Cognitive Functioning: The Role of Neighborhood Environment.

Background and Objectives: Social disconnectedness and loneliness pose significant challenges for older Chinese immigrants. Yet, it remains unclear whether they are associated with an increased risk of cognitive decline in this population. This study aimed to investigate the association of social disconnectedness and loneliness with cognitive functioning and examine the moderation role of neighborhood contexts. Research Design and Methods: This longitudinal analysis examined a sample of individuals aged 60 years and older from the Population Study of Chinese Elderly in Chicago (N = 2,044). Global cognition was assessed using the averaged z-scores of cognitive performance tests. Social disconnectedness was constructed using 5 indicators about structural aspects of social relationships. Loneliness was assessed with the R-UCLA loneliness scale. Neighborhood socioeconomic status (NSES) and neighborhood segregation index were constructed using 2010-2014 American Community Survey data at the census tract level. Individual perceptions about neighborhood environments were used to construct neighborhood cohesion index and neighborhood disorder index (NDI). Latent growth curve models with adjusted cluster robust standard errors were estimated. Results: More loneliness was associated with a higher level of initial cognitive functioning (B = 0.030, p < .01), but also with a faster decline rate over time (B = -0.007, p < .01) after adjusting for covariates. High NSES and less neighborhood segregation buffered the negative effects of loneliness on cognitive decline, respectively. High NDI amplified the positive relationship between loneliness and initial functioning, but accelerated the rate of cognitive decline associated with loneliness. Discussion and Implications: The study revealed that perceived loneliness, but not social disconnectedness, is a risk factor for cognitive decline among older Chinese immigrants. Living in a neighborhood with low socioeconomic status, more segregation, and high disorder elevated the detrimental effect of loneliness on long-term cognitive decline. Further research needs to investigate the complex interplay between social relationships, neighborhood environment, and cognition.

Para-aortic lymph node dissection with or without nerve-sparing in gynecological malignancies.

OBJECTIVE: Para-aortic lymph node dissection (PALND) is a widely used treatment that causes many complications. This study is to evaluate the efficacy and safety of nerve-sparing para-aortic lymph node dissection (NSPALND) by comparing it with conventional PALND in gynecological malignancies and to prove whether locating the superior hypogastric plexus (SHP) can help reveal the para-aortic nerves. METHODS: This is a retrospective study of the patients who underwent para-aortic lymphadenectomy from January 2020 to December 2022 at Zhejiang Cancer Hospital. All of them were divided into NSPALND and PALND groups according to whether or not nerve-sparing was performed. The surgical, functional and oncological outcomes were evaluated. RESULTS: There were 43 patients enrolled, of which, 20 patients underwent NSPALND and 23 patients underwent PALND. The para-aortic nerves were successfully revealed by locating the SHP in all 20 cases of NSPALND. The post-operative anal exhaust time in the NSPALND group was significantly shorter than that in the PALND group (2.5 vs. 4 days, p=0.006), and the incidence of acute intestinal obstruction in the NSPALND group was significantly lower than that in the PALND group (10% vs. 39%, p=0.029). There was no difference between the two groups in terms of catheterization duration, urinary retention, dysuria, as well as the number of lymph nodes removed and the para-aortic recurrence rate. CONCLUSION: NSPALND can significantly reduce the rate of acute intestinal obstruction and improve post-operative intestinal function. Locating the SHP and using it as an anatomical landmark to reveal the para-aortic nerves is feasible. Its exact clinical value needs to be further studied.

Coordination and persistence of aggressive visual communication in Siamese fighting fish.

Animals coordinate their behavior with each other during both cooperative and agonistic social interactions. Such coordination often adopts the form of "turn taking", in which the interactive partners alternate the performance of a behavior. Apart from acoustic communication, how turn taking between animals is coordinated is not well understood. Furthermore, the neural substrates that regulate persistence in engaging in social interactions are poorly studied. Here, we use Siamese fighting fish ( Betta splendens ), to study visually-driven turn-taking aggressive behavior. Using encounters with conspecifics and with animations, we characterize the dynamic visual features of an opponent and the behavioral sequences that drive turn taking. Through a brain-wide screen of neuronal activity during coordinated and persistent aggressive behavior, followed by targeted brain lesions, we find that the caudal portion of the dorsomedial telencephalon, an amygdala-like region, promotes persistent participation in aggressive interactions, yet is not necessary for coordination. Our work highlights how dynamic visual cues shape the rhythm of social interactions at multiple timescales, and points to the pallial amygdala as a region controlling engagement in such interactions. These results suggest an evolutionarily conserved role of the vertebrate pallial amygdala in regulating the persistence of emotional states.

Phosphoproteomic analysis reveals changes in A-Raf-related protein phosphorylation in response to Toxoplasma gondii infection in porcine macrophages.

BACKGROUND: Toxoplasma gondii is an obligate intracellular protozoan parasite that causes severe threats to humans and livestock. Macrophages are the cell type preferentially infected by T. gondii in vivo. Protein phosphorylation is an important posttranslational modification involved in diverse cellular functions. A rapidly accelerated fibrosarcoma kinase (A-Raf) is a member of the Raf family of serine/threonine protein kinases that is necessary for MAPK activation. Our previous research found that knockout of A-Raf could reduce T. gondii-induced apoptosis in porcine alveolar macrophages (3D4/21 cells). However, limited information is available on protein phosphorylation variations and the role of A-Raf in macrophages infected with T. gondii. METHODS: We used immobilized metal affinity chromatography (IMAC) in combination with liquid chromatography tandem mass spectrometry (LC-MS/MS) to profile changes in phosphorylation in T. gondii-infected 3D4/21 and 3D4/21-ΔAraf cells. RESULTS: A total of 1647 differentially expressed phosphorylated proteins (DEPPs) with 3876 differentially phosphorylated sites (DPSs) were identified in T. gondii-infected 3D4/21 cells (p3T group) when compared with uninfected 3D4/21 cells (pho3 group), and 959 DEPPs with 1540 DPSs were identified in the p3T group compared with infected 3D4/21-ΔAraf cells (p3KT group). Venn analysis revealed 552 DPSs corresponding to 406 DEPPs with the same phosphorylated sites when comparing p3T/pho3 versus p3T/p3KT, which were identified as DPSs and DEPPs that were directly or indirectly related to A-Raf. CONCLUSIONS: Our results revealed distinct responses of macrophages to T. gondii infection and the potential roles of A-Raf in fighting infection via phosphorylation of crucial proteins.

A unique Au-Ag-Au triangular motif in a trimetallic halonium dication: silver incorporation in a gold(I) catalyst.

As a result of explorations into the solution chemistry of silver/gold mixtures, a unique diphosphine trimetallic chloronium dication was discovered that incorporates silver-arene chelation and a triangular mixed gold/silver core in the solid state. Notably, it was isolated from a Celite prefiltered solution initially thought to be silver-free. The crystal structure also incorporates the coordination to silver of one fluorine atom of one SbF6(-) counterion. The structure was compared to two new, but well-precedented, phosphine digold chloride cations. DFT calculations supported significant silver-halide and silver-arene interactions in the mixed gold/silver complex and metallophilic interactions in all three complexes. Comparison of computed data revealed that the ωB97X-D functional, which has a long-range corrected hybrid with atom-atom dispersion corrections, gave a better fit to the experimental data compared with the PBE0 functional, which has previously failed to capture aurophilic interactions. Preliminary studies support the presence of the mixed gold/silver structure in solution.

Residential Segregation, Perceived Neighborhood Environment, and All-Cause Mortality Among Community-Dwelling Older Chinese Americans.

OBJECTIVES: Residential segregation profoundly affects mental and physical health. However, impacts of residential segregation and other neighborhood characteristics on health among older Asian Americans are not fully understood. This study aimed to close this gap by examining effects of residential segregation, perceived neighborhood cohesion, and neighborhood disorder on all-cause mortality among older Chinese immigrants, as well as testing whether the association between residential segregation and mortality would be mediated by perceived neighborhood cohesion and neighborhood disorder. METHODS: Data were drawn from a subsample of 3,094 older Chinese Americans aged 60 and older (mean age = 72.8 years) from the Population Study of Chinese Elderly in Chicago. Residential segregation was derived using 2010-2014 American Community Survey data. Participants completed surveys on perceived neighborhood cohesion and neighborhood disorder between 2011 and 2013. All-cause mortality was tracked until December 2021. RESULTS: Residential segregation was associated with elevated all-cause mortality risk; this association, however, was no longer statistically significant after controlling for sociodemographic, behavioral, and health covariates. Perceived neighborhood cohesion, but not neighborhood disorder, was significantly associated with decreased mortality risks. There were no indirect effects of residential segregation on all-cause mortality through perceived neighborhood cohesion or neighborhood disorder. These effects were consistent across male and female participants. DISCUSSION: These results suggest the importance of neighborhood social environment, specifically perceptions of neighborhood cohesion, in influencing mortality risk among older Chinese immigrants. The findings also indicate the need to conduct further research to examine the health impact of residential segregation among this population.

Effects of acute stress on risky decision-making are related to neuroticism: An fMRI study of the Balloon Analogue Risk Task.

BACKGROUND: Decision making under acute stress is frequent in daily life. While evidence suggests for a modulatory role of neuroticism on risky decision-making behaviors, the neural correlates underlying the association between neuroticism and risky decision-making under acute stress remain to be elucidated. METHODS: Based on a modified Balloon Analogue Risk Task (BART) with concurrent functional magnetic resonance imaging, we evaluated the effect of acute stress on risk-taking behavior in 27 healthy male adults, and further assessed stress-induced changes in brain activation according to the individual differences in neuroticism. RESULTS: Higher trait neuroticism levels positively correlated with increased stress-modulated activation of the right dorsal anterior cingulate cortex during risk-taking, and negatively correlated with decreased stress-modulated activation of the right dorsolateral prefrontal cortex during cash-outs. LIMITATIONS: Only male participants were recruited. CONCLUSIONS: We found a positive correlation between neuroticism and greater risk-taking behavior under acute stress. These results extend our understanding of the increased risk-taking propensity in high neurotic individuals under acute stress.

Toxoplasma gondii infection regulates apoptosis of host cells via miR-185/ARAF axis.

BACKGROUND: Toxoplasmosis is a zoonosis with a worldwide presence that is caused by the intracellular parasite Toxoplasma gondii. Active regulation of apoptosis is an important immune mechanism by which host cells resist the growth of T. gondii or avoid excessive pathological damage induced by this parasite. Previous studies found that upregulated expression of microRNA-185 (miR-185) during T. gondii infection has a potential role in regulating the expression of the ARAF gene, which is reported to be associated with cell proliferation and apoptosis. METHODS: The expression levels of miR-185 and the ARAF gene were evaluated by qPCR and Western blot, respectively, in mice tissues, porcine kidney epithelial cells (PK-15) and porcine alveolar macrophages (3D4/21) following infection with the T. gondii ToxoDB#9 and RH strains. The dual luciferase reporter assay was then used to verify the relationship between miR-185 and ARAF targets in PK-15 cells. PK-15 and 3D4/21 cell lines with stable knockout of the ARAF gene were established by CRISPR, and then the apoptosis rates of the cells following T. gondii infection were detected using cell flow cytometry assays. Simultaneously, the activities of cleaved caspase-3, as a key apoptosis executive protein, were detected by Western blot to evaluate the apoptosis levels of cells. RESULTS: Infection with both the T. gondii ToxoDB#9 and RH strains induced an increased expression of miR-185 and a decreased expression of ARAF in mice tissues, PK-15 and 3D4/21 cells. MiR-185 mimic transfections showed a significantly negative correlation in expression levels between miR-185 and the ARAF gene. The dual luciferase reporter assay confirmed that ARAF was a target of miR-185. Functional investigation revealed that T. gondii infection induced the apoptosis of PK-15 and 3D4/21 cells, which could be inhibited by ARAF knockout or overexpression of miR-185. The expression levels of cleaved caspase-3 protein were significantly lower in cells with ARAF knockout than in normal cells, which were consistent with the results of the cell flow cytometry assays. CONCLUSIONS: Toxoplasma gondii infection could lead to the upregulation of miR-185 and the downregulation of ARAF, which was not related to the strain of T. gondii and the host cells. Toxoplasma gondii infection could regulate the apoptosis of host cells via the miR-185/ARAF axis, which represents an additional strategy used by T. gondii to counteract host-cell apoptosis in order to maintain survival and reproduce in the host cells.

Effect of Driving Pressure-Oriented Ventilation on Patients Undergoing One-Lung Ventilation During Thoracic Surgery: A Systematic Review and Meta-Analysis.

Background: Hypoxemia and fluctuations in respiratory mechanics parameters are common during one-lung ventilation (OLV) in thoracic surgery. Additionally, the incidence of postoperative pulmonary complications (PPCS) in thoracic surgery is higher than that in other surgeries. Previous studies have demonstrated that driving pressure-oriented ventilation can reduce both mortality in patients with acute respiratory distress syndrome (ARDS) and the incidence of PPCS in patients undergoing general anesthesia. Our aim was to determine whether driving pressure-oriented ventilation improves intraoperative physiology and outcomes in patients undergoing thoracic surgery. Methods: We searched MEDLINE via PubMed, Embase, Cochrane, Web of Science, and ClinicalTrials.gov and performed a meta-analysis to compare the effects of driving pressure-oriented ventilation with other ventilation strategies on patients undergoing OLV. The primary outcome was the PaO2/FiO2 ratio (P/F ratio) during OLV. The secondary outcomes were the incidence of PPCS during follow-up, compliance of the respiratory system during OLV, and mean arterial pressure during OLV. Results: This review included seven studies, with a total of 640 patients. The PaO2/FiO2 ratio was higher during OLV in the driving pressure-oriented ventilation group (mean difference [MD]: 44.96; 95% confidence interval [CI], 24.22-65.70.32; I 2: 58%; P < 0.0001). The incidence of PPCS was lower (OR: 0.58; 95% CI, 0.34-0.99; I 2: 0%; P = 0.04) and the compliance of the respiratory system was higher (MD: 6.15; 95% CI, 3.97-8.32; I 2: 57%; P < 0.00001) in the driving pressure-oriented group during OLV. We did not find a significant difference in the mean arterial pressure between the two groups. Conclusion: Driving pressure-oriented ventilation during OLV in patients undergoing thoracic surgery was associated with better perioperative oxygenation, fewer PPCS, and improved compliance of the respiratory system. Systematic Review Registration: PROSPERO, identifier: CRD42021297063.