Accelerating Sulfur Redox Chemistry by Atomically Dispersed Zn-N4 Sites Coupled with Pyridine-N Defects on Porous Carbon Sheets.

Single-atom catalysts (SACs) with specific N-coordinated configurations immobilized on the carbon substrates have recently been verified to effectively alleviate the shuttle effect of lithium polysulfides (LiPSs) in lithium-sulfur (Li─S) batteries. Herein, a versatile molten salt (KCl/ZnCl2 )-mediated pyrolysis strategy is demonstrated to fabricate Zn SACs composed of well-defined Zn-N4 sites embedded into porous carbon sheets with rich pyridine-N defects (Zn─N/CS). The electrochemical kinetic analysis and theoretical calculations reveal the critical roles of Zn-N4 active sites and surrounding pyridine-N defects in enhancing adsorption toward LiPS intermediates and catalyzing their liquid-solid conversion. It is confirmed by reducing the overpotential of the rate-determining step of Li2 S2 to Li2 S and the energy barrier for Li2 S decomposition, thus the Zn─N/CS guarantees fast redox kinetics between LiPSs and Li2 S products. As a proof of concept demonstration, the assembled Li─S batteries with the Zn─N/CS-based sulfur cathode deliver a high specific capacity of 1132 mAh g-1 at 0.1 C and remarkable capacity retention of 72.2% over 800 cycles at 2 C. Furthermore, a considerable areal capacity of 6.14 mAh cm-2 at 0.2 C can still be released with a high sulfur loading of 7.0 mg cm-2 , highlighting the practical applications of the as-obtained Zn─N/CS cathode in Li─S batteries.

Click-ExM enables expansion microscopy for all biomolecules.

Expansion microscopy (ExM) allows super-resolution imaging on conventional fluorescence microscopes, but has been limited to proteins and nucleic acids. Here we develop click-ExM, which integrates click labeling into ExM to enable a 'one-stop-shop' method for nanoscale imaging of various types of biomolecule. By click labeling with biotin and staining with fluorescently labeled streptavidin, a large range of biomolecules can be imaged by the standard ExM procedure normally used for proteins. Using 18 clickable labels, we demonstrate click-ExM on lipids, glycans, proteins, DNA, RNA and small molecules. We demonstrate that click-ExM is applicable in cell culture systems and for tissue imaging. We further show that click-ExM is compatible with signal-amplification techniques and two-color imaging. Click-ExM thus provides a convenient and versatile method for super-resolution imaging, which may be routinely used for cell and tissue samples.

Arabidopsis G-protein ß subunit AGB1 represses abscisic acid signaling via attenuation of the MPK3-VIP1 phosphorylation cascade.

Heterotrimeric G proteins play key roles in cellular processes. Although phenotypic analyses of Arabidopsis Gß (AGB1) mutants have implicated G proteins in abscisic acid (ABA) signaling, the AGB1-mediated modules involved in ABA responses remain unclear. We found that a partial AGB1 protein was localized to the nucleus where it interacted with ABA-activated VirE2-interacting protein 1 (VIP1) and mitogen-activated protein kinase 3 (MPK3). AGB1 acts as an upstream negative regulator of VIP1 activity by initiating responses to ABA and drought stress, and VIP1 regulates the ABA signaling pathway in an MPK3-dependent manner in Arabidopsis. AGB1 outcompeted VIP1 for interaction with the C-terminus of MPK3, and prevented phosphorylation of VIP1 by MPK3. Importantly, ABA treatment reduced AGB1 expression in the wild type, but increased in vip1 and mpk3 mutants. VIP1 associates with ABA response elements present in the AGB1 promoter, forming a negative feedback regulatory loop. Thus, our study defines a new mechanism for fine-tuning ABA signaling through the interplay between AGB1 and MPK3-VIP1. Furthermore, it suggests a common G protein mechanism to receive and transduce signals from the external environment.

Paeoniflorin alleviated muscle atrophy in cancer cachexia through inhibiting TLR4/NF-κB signaling and activating AKT/mTOR signaling.

Cancer cachexia is a progressive wasting syndrome, which is mainly characterized by systemic inflammatory response, weight loss, muscle atrophy, and fat loss. Paeoniflorin (Pae) is a natural compound extracted from the dried root of Paeonia lactiflora Pallas, which is featured in anti-inflammatory, antioxidant, and immunoregulatory pharmacological activities. While, the effects of Pae on cancer cachexia had not been reported before. In the present study, the effects of Pae on muscle atrophy in cancer cachexia were observed both in vitro and in vivo using C2C12 myotube atrophy cell model and C26 tumor-bearing cancer cachexia mice model. In the in vitro study, Pae could alleviate myotubes atrophy induced by conditioned medium of C26 colon cancer cells or LLC Lewis lung cancer cells by decreasing the expression of Atrogin-1 and inhibited the decrease of MHC and MyoD. In the in vivo study, Pae ameliorated weight loss and improved the decrease in cross-sectional area of muscle fibers and the impairment of muscle function in C26 tumor-bearing mice. The inhibition of TLR4/NF-κB pathway and the activation of AKT/mTOR pathway was observed both in C2C12 myotubes and C26 tumor-bearing mice treated by Pae, which might be the main basis of its ameliorating effects on muscle atrophy. In addition, Pae could inhibit the release of IL-6 from C26 tumor cells, which might also contribute to its ameliorating effects on muscle atrophy. Overall, Pae might be a promising candidate for the therapy of cancer cachexia.

Inorganic Carbon Pools and Their Drivers in Grassland and Desert Soils.

Inorganic carbon is an important component of soil carbon stocks, exerting a profound influence on climate change and ecosystem functioning. Drylands account for approximately 80% of the global soil inorganic carbon (SIC) pool within the top 200 cm. Despite its paramount importance, the components of SIC and their contributions to CO2 fluxes have been largely overlooked, resulting in notable gaps in understanding its distribution, composition, and responses to environmental factors across ecosystems, especially in deserts and temperate grasslands. Utilizing a dataset of 6011 samples from 173 sites across 224 million hectares, the data revealed that deserts and grasslands in northwestern China contain 20 ± 2.5 and 5 ± 1.3 petagrams of SIC in the top 100 cm, representing 5.5 and 0.76 times the corresponding soil organic carbon stock, respectively. Pedogenic carbonates (PIC), formed by the dissolution and re-precipitation of carbonates, dominated in grasslands, accounting for 60% of SIC with an area-weighted density of 3.4 ± 0.4 kg C m-2 at 0-100 cm depth, while lithogenic carbonates (LIC), inherited from soil parent materials, prevailed in deserts, constituting 55% of SIC with an area-weighted density of 7.1 ± 1.0 kg C m-2. Soil parent materials and elevation determined the SIC stocks by regulating the formation and loss of LIC in deserts, whereas natural acidification, mainly induced by rhizosphere processes including cation uptake and H+ release as well as precipitation, reduced SIC (mainly by PIC) in grasslands. Overall, the massive SIC pool underscores its irreplaceable role in maintaining the total carbon pool in drylands. This study sheds light on LIC and PIC and highlights the critical impact of natural acidification on SIC loss in grasslands.

High-density mapping of durable and broad-spectrum stripe rust resistance gene Yr30 in wheat.

KEY MESSAGE: The durable stripe rust resistance gene Yr30 was fine-mapped to a 610-kb region in which five candidate genes were identified by expression analysis and sequence polymorphisms. The emergence of genetically diverse and more aggressive races of Puccinia striiformis f. sp. tritici (Pst) in the past twenty years has resulted in global stripe rust outbreaks and the rapid breakdown of resistance genes. Yr30 is an adult plant resistance (APR) gene with broad-spectrum effectiveness and its durability. Here, we fine-mapped the YR30 locus to a 0.52-cM interval using 1629 individuals derived from residual heterozygous F5:6 plants in a Yaco"S"/Mingxian169 recombinant inbred line population. This interval corresponded to a 610-kb region in the International Wheat Genome Sequencing Consortium (IWGSC) RefSeq version 2.1 on chromosome arm 3BS harboring 30 high-confidence genes. Five genes were identified as candidate genes based on functional annotation, expression analysis by RNA-seq and sequence polymorphisms between cultivars with and without Yr30 based on resequencing. Haplotype analysis of the target region identified six haplotypes (YR30_h1-YR30_h6) in a panel of 1215 wheat accessions based on the 660K feature genotyping array. Lines with YR30_h6 displayed more resistance to stripe rust than the other five haplotypes. Near-isogenic lines (NILs) with Yr30 showed a 32.94% higher grain yield than susceptible counterparts when grown in a stripe rust nursery, whereas there was no difference in grain yield under rust-free conditions. These results lay a foundation for map-based cloning Yr30.

Yr29 combined with QYr.nwafu-4BL.3 confers durable resistance to stripe rust in wheat cultivar Jing 411.

KEY MESSAGE: The combination of a QTL on chromosome arm 4BL and Yr29 provides durable resistance with no significant yield penalty. Wheat stripe rust or yellow rust (YR), caused by Puccinia striiformis f. sp. tritici (Pst), causes substantial yield reductions globally, but losses can be minimized by using resistance genes. Chinese wheat cultivar Jing 411 (J411) has continued to display an acceptable level of adult-plant resistance (APR) to YR in varied field conditions since its release in the 1990s. A recombinant inbred line (RIL) population comprising 187 lines developed from a cross of J411 and Kenong 9204 (KN9204) was evaluated in multiple environments to identify genomic regions carrying genes for YR resistance. A total of five quantitative trait loci (QTL) on chromosome arm 1BL, 3BS, 4BL, 6BS, and 7BL from J411 and two QTL on 3DS and 7DL from KN9204 were detected using inclusive composite interval mapping with the wheat 660 K SNP array. QYr.nwafu-1BL.5 and QYr.nwafu-4BL.3 from J411 were robust and showed similar effects in all environments. QYr.nwafu-1BL.5 was likely the pleiotropic gene of Yr29/Lr46. QYr.nwafu-4BL.3 was located within a 1.0 cM interval delimited by KASP markers AX-111609222 and AX-89755491. Based on haplotype analysis, Yr29 and QYr.nwafu-4BL.3 were identified as genetic components of quantitative resistance in a number of wheat cultivars. Moreover, RILs with Yr29 and QYr.nwafu-4BL.3 individually or when combined showed higher resistance to YR in rust nurseries compared with RILs without them, and there was no negative effect of their presence on agronomic traits under rust-free conditions. These results suggest that effective polymerization strategy is important for breeding high yielding and durable resistance cultivars.

Screening results and mutation frequency analysis of G6PD deficiency in 1,291,274 newborns in Huizhou, China: a twenty-year experience.

OBJECTIVES: This study aimed to investigate the incidence rate and spectrum of gene mutations of Glucose-6-phosphate dehydrogenase (G6PD) deficiency in the Huizhou city of southern China to provide a scientific basis for disease prevention and control in the area. METHODS: From March 2003 to December 2022, newborn screening for G6PD enzyme activity was carried out in Huizhou city using the fluorescence quantitative method. Infants who tested positive during the initial screening were diagnosed using the nitroblue tetrazolium ratio method, while a subset of infants received further gene mutation analysis using the multicolor probe melting curve analysis method. RESULTS: A total of 1,291,274 newborns were screened and the screening rate has increased from 20.39% to almost 100%. In the 20-year period, 57,217 (4.43%) infants testing positive during the initial screening. Out of these infants, 49,779 (87%) were recalled for confirmatory testing. G6PD deficiency was confirmed in 39,261 of the recalled infants, indicating a positive predictive value of 78.87%. The estimated incidence rate of G6PD deficiency in the region was 3.49%, which was significantly higher than the average incidence rate of 2.1% in southern China. On the other hand, seven pathogenic G6PD variants were identified in the analysis of the 99 diagnosed infants with the most common being c.1388 G > A (48.5%), followed by c.95 A > G (19.2%), c.1376 G > T (15.2%), c.871 G > A (9.1%), c.1360 C > T (3.0%), c.392 G > T (3.0%), and c.487 G > A (1.0%). CONCLUSION: The incidence of G6PD deficiency in newborns in the Huizhou city was higher than the southern China average level, while the types and frequencies of gene mutations were found to vary slightly from other regions. Our findings suggested that free government screening and nearby diagnosis strategies could reduce the incidence of G6PD deficiency in the area.

Interleukin-22 induces interleukin-18 expression from epithelial cells during intestinal infection.

T helper 1 (Th1) cell-associated immunity exacerbates ileitis induced by oral Toxoplasma gondii infection. We show here that attenuated ileitis observed in interleukin-22 (IL-22)-deficient mice was associated with reduced production of Th1-cell-promoting IL-18. IL-22 not only augmented the expression of Il18 mRNA and inactive precursor protein (proIL-18) in intestinal epithelial cells after T. gondii or Citrobacter rodentium infection, but also maintained the homeostatic amount of proIL-18 in the ileum. IL-22, however, did not induce the processing to active IL-18, suggesting a two-step regulation of IL-18 in these cells. Although IL-18 exerted pathogenic functions during ileitis triggered by T. gondii, it was required for host defense against C. rodentium. Conversely, IL-18 was required for the expression of IL-22 in innate lymphoid cells (ILCs) upon T. gondii infection. Our results define IL-18 as an IL-22 target gene in epithelial cells and describe a complex mutual regulation of both cytokines during intestinal infection.

A Concise Synthesis of (2R,6R)-Hydroxynorketamine.

A concise synthesis of (2R,6R)-hydroxynorketamine was accomplished in eight steps, starting from commercially available materials. This synthesis features a cerium chloride-enhanced Stork-Danheiser reaction, an asymmetric reduction of ketone by the Corey-Bakshi-Shibata reaction, a signature Overman rearrangement, and a facial selective dihydroxylation of an electronically deficient olefin by RuCl3/NaIO4. The overall yield is 7.3% with 94.5% ee.

Effects of oxygen adsorption on the corrosion behavior of the Ti(0001) surface: a DFT investigation.

The electrochemical corrosion of Ti surfaces is significantly affected by O adsorption, yet the underlying mechanisms remain unexplored. Herein, density functional theory calculations are employed to examine the adsorption energies, structural properties, electronic structures, and thermodynamic stability of atomic O on Ti(0001) surfaces during initial oxidation. Additionally, the impact of O adsorption on Ti dissolution is assessed by introducing a Ti vacancy on the Ti(0001) surface. The passivation of the Ti(0001) surface is predominantly ascribed to the robust adsorption of O atoms. The thermodynamic results reveal that bulk TiO2 easily forms at 300 K, which explains the spontaneous passivation of the Ti(0001) surface. The formation of an O monolayer on the Ti(0001) surface increases the work function (Φ), positively shifting the equilibrium potential and reducing the corrosion rate. The surface vacancy formation energy of Ti on the Ti(0001)/O surface surpasses that on the clean surface. The electrode potential shift for a Ti atom dissolving from the Ti(0001)/O surface is positive, indicating that oxidation impedes the formation of Ti vacancies, rendering Ti atoms less soluble. This study enhances our comprehension of the corrosion mechanism in Ti metal.

Effects of adsorption of O2 and H2O molecules on the corrosion behavior of the NiTi alloy surface: a DFT investigation.

The influence of O2 and H2O adsorption significantly affects the electrochemical corrosion of the NiTi alloy, with unresolved corrosion disparities between the NiTi-B2 and NiTi-B19' phases. Density functional theory (DFT) calculations are utilized in this investigation to explore the adsorption of O atoms at varying coverages on the NiTi-B2(110) and NiTi-B19'(010) surfaces. The goal is to elucidate their oxidation behavior differences. Subsequently, the effect of O adsorption on the dissolution trends of these phases is assessed by inducing Ni/Ti vacancies to simulate alloy dissolution thermodynamically. Additionally, interactions between H2O molecules and O-pre-adsorbed NiTi alloy surfaces are examined to simulate the atomic evolution of the oxidized surface under exposure to humid air and corrosive solutions. The findings indicate a propensity of the NiTi-B19' phase to react with O, forming an oxide film more readily than the NiTi-B2 phase. O adsorption facilitates Ni dissolution and retards Ti dissolution on the alloy surface. Higher O coverage promotes easier dissolution of Ni and Ti atoms on the NiTi-B2(110) surface compared to the NiTi-B19'(010) surface, underscoring the greater corrosion resistance of the NiTi-B19' phase. Both clean and O-pre-adsorbed NiTi alloy surfaces physically adsorb H2O molecules. Notably, an O monolayer substantially mitigates the detrimental effects of H2O molecules on the corrosion resistance of alloy surfaces. This research contributes to a deeper comprehension of the corrosion mechanisms in NiTi alloys.

High Respiratory and Cardiac Drive Exacerbate Secondary Lung Injury in Patients With Critical Illness.

The high respiratory and cardiac drive is essential to the host-organ unregulated response. When a primary disease and an unregulated secondary response are uncontrolled, the patient may present in a high respiratory and cardiac drive state. High respiratory drive can cause damage to the lungs, pulmonary circulation, and diaphragm, while high cardiac drive can lead to fluid leakage and infiltration as well as pulmonary interstitial edema. A "respiratory and cardiac dual high drive" state may be a sign of an unregulated response and can lead to secondary lung injury through the increase of transvascular pressure and pulmonary microcirculation injury. Ultrasound examination of the lung, heart, and diaphragm is important when evaluating the phenotype of high respiratory drive in critically ill patients. Ultrasound assessment can guide sedation, analgesia, and antistress treatment and reduce the risk of high respiratory and cardiac drive-induced lung injury in these patients.

Prospective Evaluation of the Peripheral Perfusion Index in Assessing the Organ Dysfunction and Prognosis of Adult Patients With Sepsis in the ICU.

Background: The peripheral perfusion index (PI) reflects microcirculatory blood flow perfusion and indicates the severity and prognosis of sepsis. Method: The cohort comprised 208 patients admitted to the intensive care unit (ICU) with infection, among which 117 had sepsis. Demographics, medication history, ICU variables, and laboratory indexes were collected. Primary endpoints were in-hospital mortality and 28-day mortality. Secondary endpoints included organ function variables (coagulation function, liver function, renal function, and myocardial injury), lactate concentration, mechanical ventilation time, and length of ICU stay. Univariate and multivariate analyses were conducted to assess the associations between the PI and clinical outcomes. Sensitivity analyses were performed to explore the associations between the PI and organ functions in the sepsis and nonsepsis groups. Result: The PI was negatively associated with in-hospital mortality (odds ratio [OR] 0.29, 95% confidence interval [CI] 0.15 to 0.55), but was not associated with 28-day mortality. The PI was negatively associated with the coagulation markers prothrombin time (PT) (ß -0.36, 95% CI -0.59 to 0.13) and activated partial thromboplastin time (APTT) (ß -1.08, 95% CI -1.86 to 0.31), and the myocardial injury marker cardiac troponin I (cTnI) (ß -2085.48, 95% CI -3892.35 to 278.61) in univariate analysis, and with the PT (ß -0.36, 95% CI -0.60 to 0.13) in multivariate analysis. The PI was negatively associated with the lactate concentration (ß -0.57, 95% CI -0.95 to 0.19), mechanical ventilation time (ß -23.11, 95% CI -36.54 to 9.69), and length of ICU stay (ß -1.28, 95% CI -2.01 to 0.55). Sensitivity analyses showed that the PI was significantly associated with coagulation markers (PT and APTT) and a myocardial injury marker (cTnI) in patients with sepsis, suggesting that the associations between the PI and organ function were stronger in the sepsis group than the nonsepsis group. Conclusion: The PI provides new insights for assessing the disease severity, short-term prognosis, and organ function damage in ICU patients with sepsis, laying a theoretical foundation for future research.

A nomogram for predicting postpartum post-traumatic stress disorder: a prospective cohort study.

BACKGROUND: Postpartumpost-traumatic stress disorder (PTSD), as a psychological stress disorder, has long-term and widespread harm. Still, compared with other postpartum psychiatric disorders, postpartum PTSD has received relatively littleattention in China. This study aims to investigate the risk factors of postpartum PTSD and to develop a convenient and rapid nomogram screening tool to help clinical staff identify high-risk pregnant womenin time and take preventative and management measures. METHODS: Recruited pregnant women hospitalized for delivery in Qingdao Municipal Hospital and Jinzhou Maternal and Child Health Hospital from November 2022 to October 2023 as convenient samples for the questionnaire survey. Telephone follow-up was conducted 42 days after delivery. After univariate analysis, multicollinearity analysis, and logistic regression analysis, the risk factors of postnatal PTSD were obtained, a prediction model was established, and a nomogram was drawn by R software. G*power3.1.9.7 calculated the effectiveness of the test. The model was validated internally using the Bootstrap approach, and external validation was carried out using a verification group. The accuracy of the model's predictions and its clinical application value were evaluated by the area under the curve, calibration plot, and decision curve analysis. RESULTS: A total of 602 women were recruited in this study, and the incidence of postpartum PTSD was 11.1% (67/602). Multifactorial logistic regression analysis showed that poor self-assessment of sleep status in late pregnancy (OR = 5.336), cesarean section (OR = 2.825), instrumental delivery (OR = 5.994), having fear of labor (OR = 4.857), and a high score of Five Factors Inventory Neuroticism subscale (OR = 1.244) were independent risk factors for developing postpartum PTSD. A high Quality of Relationship Index score (OR = 0.891) was a protective factor for postpartum PTSD. In the training and validation sets, the nomogram model's area under the ROC curve was 0.928 and 0.907, respectively. The calibration curves showed that the nomogram model was well-fitted, and the Decision Curve Analysis indicated that the nomogram model had good value for clinical application. CONCLUSIONS: With its strong predictive capacity, the prediction model built using postpartum PTSD risk factors can help clinical caregivers identify high-risk pregnant women early on and implement timely preventive intervention strategies.

Psychometric characteristics of the Chinese version of the Pregnancy Exercise Attitudes Scale (C-PEAS).

BACKGROUND: Reasonable instruction and promotion of appropriate exercise are crucial to improving the exercise status of pregnant women and safeguarding the health of both mother and fetus. However, there is a lack of validated Pregnancy Exercise Attitude Scales with a complete evaluation system in China. This study aims to assess the validity and reliability of the Pregnancy Exercise Attitude Scale (C-PEAS) in Chinese to give medical professionals a reference for carrying out pregnancy care services and promoting the health of the mother and fetus. METHODS: In this study, the scale was translated, back-translated, and cross-culturally adapted using the Brislin translation model to form the C-PEAS. 528 pregnant women were conveniently selected for the questionnaire survey to evaluate the scale's reliability. The scale's content validity was assessed by the content validity index, while its structural validity was investigated using exploratory factor analysis (EFA) and confirmatory factor analysis (CFA). Cronbach's alpha coefficient, McDonald's omega coefficient, split-half reliability, and retest reliability were used to evaluate the scale's internal consistency. RESULTS: The C-PEAS contains two dimensions with 37 entries. The EFA supports a two-factor structure with a cumulative variance contribution of 62.927%. The CFA model was well fitted (χ2/df = 1.597, RMSEA = 0.048, IFI = 0.955, TLI = 0.952, and CFI = 0.955). The C- PEAS' Cronbach's alpha coefficient was 0.973, and the range of Cronbach's alpha values for the dimensions was 0.976, 0.944. McDonald's omega coefficient was 0.971, the half-point reliability of the scale was 0.856, and the retest reliability was 0.966. CONCLUSIONS: The Chinese version of C-PEAS has good psychometric properties. It can be used as an effective measurement tool to evaluate the attitude of pregnant women to exercise during pregnancy.

The level of partial pressure of carbon dioxide affects organ perfusion in respiratory failure patients undergoing pressure support ventilation with venovenous extracorporeal membrane oxygenation: a prospective study.

BACKGROUND: We evaluated the influence of different partial carbon dioxide pressure (PaCO2) levels on organ perfusion in patients with respiratory failure receiving pressure-support ventilation with veno-venous extracorporeal membrane oxygenation (V-V ECMO). METHODS: In this twelve patients prospective study, ECMO gas-flow was decreased from baseline (PaCO2 < 40 mmHg) until PaCO2 increased by 5-10 mmHg (High-CO2 phase). Resistance indices of gut, spleen, and snuffbox artery, the peripheral perfusion index (PPI), and heart rate variability were measured at baseline and High-CO2 phase. RESULTS: When PaCO2 increased from 36 (36-37) mmHg at baseline to 42 (41-43) mmHg in the High-CO2 phase (p < 0.001), PPI decreased significantly (p = 0.026). The snuffbox artery (p = 0.022), superior mesenteric artery (p = 0.042), and spleen (p = 0.012) resistance indices increased significantly. The root mean square of successive differences (RMSSD) decreased from 19.5(18.1-22.7) to 15.9(14.4-18.6) ms (p = 0.034), and the ratio of low-frequency to high-frequency components(LF/HF) increased from 0.47 ± 0.23 to 0.70 ± 0.38 (p = 0.013). CONCLUSIONS: High PaCO2 might cause decreased peripheral tissue and visceral organ perfusion through autonomic nervous system in patients with respiratory failure undergoing PSV with V-V ECMO.

Echocardiographic features of right ventricle in septic patients with elevated central venous pressure.

BACKGROUND: Elevated central venous pressure (CVP) is deemed as a sign of right ventricular (RV) dysfunction. We aimed to characterize the echocardiographic features of RV in septic patients with elevated CVP, and quantify associations between RV function parameters and 30-day mortality. METHODS: We retrospectively reviewed a cohort of septic patients with CVP ≥ 8 mmHg in a tertiary hospital intensive care unit. General characteristics and echocardiographic parameters including tricuspid annular plane systolic excursion (TAPSE), pulmonary vascular resistance (PVR) as well as prognostic data were collected. Associations between RV function parameters and 30-day mortality were assessed using Cox regression models. RESULTS: Echocardiography was performed in 244 septic patients with CVP ≥ 8 mmHg. Echocardiographic findings revealed that various types of abnormal RV function can occur individually or collectively. Prevalence of RV systolic dysfunction was 46%, prevalence of RV enlargement was 34%, and prevalence of PVR increase was 14%. In addition, we collected haemodynamic consequences and found that prevalence of systemic venous congestion was 16%, prevalence of RV-pulmonary artery decoupling was 34%, and prevalence of low cardiac index (CI) was 23%. The 30-day mortality of the enrolled population was 24.2%. In a Cox regression analysis, TAPSE (HR:0.542, 95% CI:0.302-0.972, p = 0.040) and PVR (HR:1.384, 95% CI:1.007-1.903, p = 0.045) were independently associated with 30-day mortality. CONCLUSIONS: Echocardiographic findings demonstrated a high prevalence of RV-related abnormalities (RV enlargement, RV systolic dysfunction and PVR increase) in septic patients with elevated CVP. Among those echocardiographic parameters, TAPSE and PVR were independently associated with 30-day mortality in these patients.

The level of partial pressure of carbon dioxide affects respiratory effort in COVID-19 patients undergoing pressure support ventilation with extracorporeal membrane oxygenation.

BACKGROUND: Patients with COVID-19 undergoing pressure support ventilation (PSV) with extracorporeal membrane oxygenation (ECMO) commonly had high respiratory drive, which could cause self-inflicted lung injury. The aim of this study was to evaluate the influence of different levels of partial pressure of carbon dioxide(PaCO2) on respiratory effort in COVID-19 patients undergoing PSV with ECMO. METHODS: ECMO gas flow was downregulated from baseline (respiratory rate < 25 bpm, peak airway pressure < 25 cm H2O, tidal volume < 6 mL/kg, PaCO2 < 40 mmHg) until PaCO2 increased by 5 - 10 mmHg. The pressure muscle index (PMI) and airway pressure swing during occlusion (ΔPOCC) were used to monitor respiratory effort, and they were measured before and after enforcement of the regulations. RESULTS: Ten patients with COVID-19 who had undergone ECMO were enrolled in this prospective study. When the PaCO2 increased from 36 (36 - 37) to 42 (41-43) mmHg (p = 0.0020), there was a significant increase in ΔPOCC [from 5.6 (4.7-8.0) to 11.1 (8.5-13.1) cm H2O, p = 0.0020] and PMI [from 3.0 ± 1.4 to 6.5 ± 2.1 cm H2O, p < 0.0001]. Meanwhile, increased inspiratory effort determined by elevated PaCO2 levels led to enhancement of tidal volume from 4.1 ± 1.2 mL/kg to 5.3 ± 1.5 mL/kg (p = 0.0003) and respiratory rate from 13 ± 2 to 15 ± 2 bpm (p = 0.0266). In addition, the increase in PaCO2 was linearly correlated with changes in ΔPOCC and PMI (R2 = 0.7293, p = 0.0003 and R2 = 0.4105, p = 0.0460, respectively). CONCLUSIONS: In patients with COVID-19 undergoing PSV with ECMO, an increase of PaCO2 could increase the inspiratory effort.

Transcriptional regulation of intermolecular Ca2+ signaling in hibernating ground squirrel cardiomyocytes: The myocardin-junctophilin axis.

The contraction of heart cells is controlled by the intermolecular signaling between L-type Ca2+ channels (LCCs) and ryanodine receptors (RyRs), and the nanodistance between them depends on the interaction between junctophilin-2 (JPH2) in the sarcoplasmic reticulum (SR) and caveolin-3 (CAV3) in the transversal tubule (TT). In heart failure, decreased expression of JPH2 compromises LCC-RyR communication leading to deficient blood-pumping power. In the present study, we found that JPH2 and CAV3 transcription was concurrently regulated by serum response factor (SRF) and myocardin. In cardiomyocytes from torpid ground squirrels, compared with those from euthermic counterparts, myocardin expression was up-regulated, which boosted both JPH2 and CAV3 expression. Transmission electron microscopic imaging showed that the physical coupling between TTs and SRs was tightened during hibernation and after myocardin overexpression. Confocal Ca2+ imaging under the whole-cell patch clamp condition revealed that these changes enhanced the efficiency of LCC-RyR intermolecular signaling and fully compensated the adaptive down-regulation of LCCs, maintaining the power of heart contraction while avoiding the risk of calcium overload during hibernation. Our finding not only revealed an essential molecular mechanism underlying the survival of hibernating mammals, but also demonstrated a "reverse model of heart failure" at the molecular level, suggesting a strategy for treating heart diseases.