Carbapenem-Resistant Pseudomonas aeruginosa Infection and Mixed Infections Are Risk Factors for Poor Outcome After Lung Transplant.

OBJECTIVES: In this study, we analyzed the effects of carbapenem-resistant Pseudomonas aeruginosa infection and mixed infection on the perioperative prognosis of lung transplant recipients and studied statistics on antibiotic resistance in P aeruginosa. MATERIALS AND METHODS: This was a retrospective casecontrol study. We collected data on lung transplant recipients with combined lower respiratory tract P aeruginosa infection within 48 hours after lung transplant at the China-Japan Friendship Hospital from August 2018 to April 2022. We grouped recipients according to P aeruginosa resistance to carbapenem antibiotics and summarized the clinical characteristics of carbapenem-resistant P aeruginosa infection. We analyzed the effects of carbapenemresistant P aeruginosa infection and mixed infections on all-cause mortality 30 days after lung transplant by Cox regression. We used the Kaplan-Meier method to plot survival curves. RESULTS: Patients in the carbapenem-resistant P aeruginosa group had a higher all-cause mortality rate than those in the carbapenem-sensitive P aeruginosa group at both 7 days (6 patients [22.3%] vs 2 patients [4.5%]; P = .022) and 30 days (12 patients [44.4%] vs 7 patients [15.9%]; P = .003) after lung transplant. In multivariate analysis, both carbapenemresistant P aeruginosa infection and P aeruginosa combined with bacterial infection were independent risk factors for death 30 days after transplant in lung transplant recipients (P < .05). In subgroup analysis, carbapenem-resistant P aeruginosa combined with bacterial infection increased the risk of death 30 days after transplant in lung transplant recipients compared with carbapenem-sensitive P aeruginosa combined with bacterial infection (12 patients [60%] vs 6 patients [19.4%]; P < .001). CONCLUSIONS: Combined lower respiratory tract carbapenem-resistant P aeruginosa infection and P aeruginosa combined with bacterial infection early after lung transplant increased the risk of 30-day mortality after lung transplant.

Association between the lung microbiome and perioperative prognosis in lung transplant recipients.

RATIONALE: Studies have confirmed that the lung microbiome of lung transplant recipients is altered and serves as a prognostic indicator for long-term mortality. Other studies reported that the lung microbiome affects host immunity and the transcriptome. However, the lung microbiome composition at the early post-transplant period following lung transplantation is unclear, and the relationship of the lung microbiome with pulmonary immunity and the host transcriptome is also not well understood. OBJECTIVES: We hypothesize that changes in the lung microbiome composition in the early post-transplant period may have a predictive value for perioperative outcomes following lung transplantation and that the lung microbiome is correlated with pulmonary immunity and the host transcriptome. Thus, this prospective study aimed at observing the lung microbiome composition in the early post-transplant period and the impact of the lung microbiome on pulmonary cytokines and the host transcriptome. Our findings will help us gain a comprehensive understanding of the distribution and significance of the lung microbiome in the early post-transplant period. METHODS: An observational study was conducted to identify the lung microbiome and the host transcriptome characteristics using next-generation sequencing. Luminex was employed for quantifying alveolar cytokines. Spearman's correlation analysis was utilized to assess the impact of the lung microbiome on pulmonary immunity and differentially expressed genes in patients who died perioperatively after lung transplantation. RESULTS: Patients with poor perioperative outcomes showed an increase in Mycoplasma and Arcobacter, a decrease of Gemella, and increased interleukin (IL)-10, IL-1ß, and tumor necrosis factor (TNF)-α concentration. The lung microbiome correlates with lung immunity in lung transplant recipients. In the death group, the function of differentially expressed genes is associated with cell apoptosis, and promoting TNF production is upregulated. The lung microbiome is related to differentially expressed genes between the two groups. CONCLUSIONS: The lung microbiome and cytokines can be considered as potential biomarkers for early prognosis in lung transplant recipients. The lung microbiome is associated with both lung immunity and differentially expressed genes in lung transplant recipients.

Mycorrhizal mediation of soil carbon in permafrost regions depends on soil nutrient stoichiometry and physical protection.

Mycorrhizal associations are considered as one of the key drivers for soil carbon (C) accumulation and stability. However, how mycorrhizal associations influence soil organic C (SOC) and its fractions (i.e., particulate organic C [POC] and mineral-associated organic C [MAOC]) remain unclear. In this study, we examined effects of plant mycorrhizal associations with arbuscular mycorrhiza (AM), ectomycorrhiza (ECM), and their mixture (Mixed) on SOC and its fractions as well as soil stoichiometric ratios across 800-km transect in permafrost regions. Our results showed that soil with only ECM-associated trees had significantly higher SOC and POC compared to only AM-associated tree species, while soil in Mixed plots with both AM- and ECM- associated trees tend to be somewhat in the middle. Using structural equation models, we found that mycorrhizal association significantly influenced SOC and its fraction (i.e., POC, MAOC) indirectly through soil stoichiometric ratios (C:N, C:P, and N:P). These results suggest that selecting ECM tree species, characterized by a "slow cycling" nutrient uptake strategy, can effectively enhance accumulation of SOC and its fractions in permafrost forest ecosystems. Our findings provide novel insights for quantitatively assessing the influence of mycorrhiza-associated tree species on the management of soil C pool and biogeochemical cycling.

Risk factors and the value of microbiological examinations of COVID-19 associated pulmonary aspergillosis in critically ill patients in intensive care unit: the appropriate microbiological examinations are crucial for the timely diagnosis of CAPA.

Introduction: During the Omicron pandemic in China, a significant proportion of patients with Coronavirus Disease 2019 (COVID-19) associated pulmonary aspergillosis (CAPA) necessitated admission to intensive care unit (ICU) and experienced a high mortality. To explore the clinical risk factors and the application/indication of microbiological examinations of CAPA in ICU for timely diagnosis are very important. Methods: This prospective study included patients with COVID-19 admitted to ICU between December 1, 2022, and February 28, 2023. The clinical data of influenza-associated pulmonary aspergillosis (IAPA) patients from the past five consecutive influenza seasons (November 1, 2017, to March 31, 2022) were collected for comparison. The types of specimens and methods used for microbiological examinations were also recorded to explore the efficacy in early diagnosis. Results: Among 123 COVID-19 patients, 36 (29.3%) were diagnosed with probable CAPA. CAPA patients were more immunosuppressed, in more serious condition, required more advanced respiratory support and had more other organ comorbidities. Solid organ transplantation, APACHEII score ≥20 points, 5 points ≤SOFA score <10 points were independent risk factors for CAPA. Qualified lower respiratory tract specimens were obtained from all patients, and 84/123 (68.3%) patients underwent bronchoscopy to obtain bronchoalveolar lavage fluid (BALF) specimens. All patients' lower respiratory tract specimens underwent fungal smear and culture; 79/123 (64.2%) and 69/123 (56.1%) patients underwent BALF galactomannan (GM) and serum GM detection, respectively; metagenomic next-generation sequencing (mNGS) of the BALF was performed in 62/123 (50.4%) patients. BALF GM had the highest diagnostic sensitivity (84.9%), the area under the curve of the mNGS were the highest (0.812). Conclusion: The incidence of CAPA was extremely high in patients admitted to the ICU. CAPA diagnosis mainly depends on microbiological evidence owing to non-specific clinical manifestations, routine laboratory examinations, and CT findings. The bronchoscopy should be performed and the BALF should be obtained as soon as possible. BALF GM are the most suitable microbiological examinations for the diagnosis of CAPA. Due to the timely and accuracy result of mNGS, it could assist in early diagnosis and might be an option in critically ill CAPA patients.

Clinical and Temporal Radiological Findings from Critical Patients with COVID-19 Pneumonia: A Descriptive Study.

BACKGROUND: In late December 2019, Wuhan, the capital of Hubei Province, China, became the center of an outbreak of pneumonia caused by severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2). INTRODUCTION: The radiological changes in the lungs of critical people with coronavirus disease 2019 (COVID-19) pneumonia at different times have not been fully characterized. We aim to describe the computed tomography findings of patients with critical COVID-19 pneumonia at different disease stages. METHODS: Clinical and laboratory features of critical patients were assessed. CT scans were assigned to groups 1, 2, 3, or 4 based on the interval from symptom onset (within 2 weeks; ≥ 2-4 weeks; ≥ 4-6 weeks; or ≥ 6 weeks, respectively). Imaging features were analyzed and compared across the four groups. Total CT scores, corresponding periods of laboratory findings, and glucocorticoid dosages during the imaging intervals were longitudinally observed in five patients with complete data. RESULTS: All 11 critical patients (median age: 60 years [42-69]) underwent a total of 40 CT examinations, and the acquisition times ranged from 1-59 days after symptom onset. Median total CT scores were 18 (9-25.25); 44.5 (42.88-47.62); 43.75 (38.62-49.38); and 42 (32.25-53.25) in groups 1, 2, 3, and 4, respectively. The observed lesions were mainly bilateral (37 [92.5%]). The median values of involved lung segments were 10.5 (4.5-13.5); 17 (16-18.5); 18 (18-19.5); and 18 (18-19) in groups 1-4, respectively. The predominant patterns of observed abnormalities were ground-glass opacities (GGO) (9 [90%]); GGO with reticulation and mixed patterns (3 [37.5%] for both); GGO with consolidation (3 [30%]); and GGO with reticulation (8 [66.7%]) in groups 1-4, respectively. Patients developed fibrotic manifestations at later stages. CONCLUSION: Critical patients with COVID-19 infection generally presented with temporally changing abnormal CT features from focal unilateral to diffuse bilateral GGO and consolidation that progressed to or coexisted with reticulation in the long term after symptom onset. Low-dose glucocorticoids may be effective in patients with interstitial changes on CT findings.

The role of lung microbiota in primary graft dysfunction in lung transplant recipients.

BACKGROUND: Recent studies have shown that the lung microbiota is altered in critically ill patients and predicts clinical outcomes. Primary graft dysfunction (PGD) is a common complication and a leading cause of death within 1 month of lung transplantation, but the clinical significance of changes in the lung bacterial community during PGD is unclear. The aim of this study was to determine the contribution of the lung microbiota to the development and course of severe PGD. METHODS: We conducted a retrospective study to characterize the lung microbiota of 32 lung transplant patients with combined PGD using next-generation sequencing of bronchoalveolar lavage samples. The relationship between lung flora dysbiosis and lung immunity in PGD was assessed by quantification of alveolar cytokines. The contribution of microbiota characteristics to patient outcomes was assessed by estimating overall survival. RESULTS: Patients diagnosed with PGD grade 3 showed a reduction in alpha diversity, driven by a significant increase in the abundance of the genera Modestobacter, Scardovia and Selenomonas, and a reduction in the proportion of the genera Klebsiella and Oribacterium. Alpha diversity of the lung microbiota in PGD3 patients was negatively correlated with BALF interleukin (IL)-2 (r = -.752, p < .05). In addition, bacterial diversity in the lung microbiota of non-survivors was lower than that of survivors (p = .041). CONCLUSIONS: There is variation in the lung microbiota of PGD grade 3 patients and dysbiosis of the lung microbiota is associated with lung immunity. The lung microbiota has potential in the diagnosis and treatment of PGD grade 3.

Effects of nitrogen addition on greenhouse gas fluxes during continuous freeze-thaw cycles in a cold temperate forest.

Both nitrogen (N) deposition and soil freeze-thaw cycles (FTCs) induce pulses of greenhouse gas (GHG) emissions in cold temperate zones due to changes in soil carbon (C) and nitrogen (N) turnover. However, the combined effects of N addition and FTCs on GHG fluxes have received little research attention, particularly in boreal forests. We conducted a laboratory incubation experiment using intact soil cores from Rhododendron dauricum-Larix dahurica plots to investigate the GHG flux response to these combined effects. We separated the soil samples into seven groups (no, low, medium, and high sodium nitrate addition and low, medium, and high ammonium chloride addition) and exposed each group to continuous FTC conditions. The N2O and CO2 emissions were eventually stimulated by the FTCs, while CH4 uptake was inhibited by FTCs but responded differently under different N addition treatments. All the treatments had substantially increased N2O emissions compared to the control. However, the soil respiration rate significantly increased only with medium sodium nitrate addition, and high levels of N addition (regardless of form) inhibited CH4 uptake. These findings demonstrate that FTCs and N addition (in various forms and levels) have considerable effects on GHG emissions in temperate forest ecosystems. Moreover, dissolved organic carbon (DOC), microbial biomass carbon (MBC), microbial biomass nitrogen (MBN), and inorganic nitrogen in soil are potential factors that drive GHG emissions and are necessary considerations in predicting future feedback effects of GHG emissions on climate change.

Responses of soil enzyme activity to freeze-thaw alternation in Greater Khingan Mountains, China.

We examined the effects of freeze-thaw cycles (0, 1, 3, 5, 7, 15 cycles) on the activities of urease, invertase, and proteinase in the different layers of the soil under the four typical stands in the cold temperate zone, i.e., Pinus pumila stand, Rhododendron-Betula platyphylla stand, Rhododendron-Larix gmelinii stand, Ledum-Larix gmelinii stand, with the indoor freeze-thaw simulation culture method being used. The relationship between soil enzyme activity and multiple physicochemical variables was analyzed during freeze-thaw alternation. The results showed that the activity of soil urease was firstly increased and then inhibited during freeze-thaw alternation. After freeze-thaw, urease activity did not differ from that without freeze-thaw. Invertase activity was firstly inhibited and then increased during freeze-thaw alternation, and was significantly increased by 8.5%-40.3% after freeze-thaw. Proteinase activity was firstly increased and then inhibited during freeze-thaw alternation, and was significantly decreased by 13.8%-68.9% after freeze-thaw. After freezing and thawing, there was significant positive correlation between urease activity and ammonium nitrogen and soil water content in Ledum-L. gmelinii stand and P. pumila stand, respectively, and proteinase activity had significant negative correlation with inorganic nitrogen concentration in P. pumila stand, Rhododendron-B. platyphylla stand, and Ledum-L. gmelinii stand. Invertase activity had significant positive correlation with organic matter in Rhododendron-L. gmelinii stand and Ledum-L. gmelinii stand.

The shift of soil microbial community induced by cropping sequence affect soil properties and crop yield.

Rational cropping maintains high soil fertility and a healthy ecosystem. Soil microorganism is the controller of soil fertility. Meanwhile, soil microbial communities also respond to different cropping patterns. The mechanisms by which biotic and abiotic factors were affected by different cropping sequences remain unclear in the major grain-producing regions of northeastern China. To evaluate the effects of different cropping sequences under conventional fertilization practices on soil properties, microbial communities, and crop yield, six types of plant cropping systems were performed, including soybean monoculture, wheat-soybean rotation, wheat-maize-soybean rotation, soybean-maize-maize rotation, maize-soybean-soybean rotation and maize monoculture. Our results showed that compared with the single cropping system, soybean and maize crop rotation in different combinations or sequences can increase soil total organic carbon and nutrients, and promote soybean and maize yield, especially using soybean-maize-maize and maize-soybean-soybean planting system. The 16S rRNA and internal transcribed spacer (ITS) amplicon sequencing showed that different cropping systems had different effects on bacterial and fungal communities. The bacterial and fungal communities of soybean monoculture were less diverse when compared to the other crop rotation planting system. Among the different cropping sequences, the number of observed bacterial species was greater in soybean-maize-maize planting setup and fungal species in maize-soybean-soybean planting setup. Some dominant and functional bacterial and fungal taxa in the rotation soils were observed. Network-based analysis suggests that bacterial phyla Acidobacteria and Actinobacteria while fungal phylum Ascomycota showed a positive correlation with other microbial communities. The phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt) result showed the presence of various metabolic pathways. Besides, the soybean-maize-maize significantly increased the proportion of some beneficial microorganisms in the soil and reduced the soil-borne animal and plant pathogens. These results warrant further investigation into the mechanisms driving responses of beneficial microbial communities and their capacity on improving soil fertility during legume cropping. The present study extends our understanding of how different crop rotations effect soil parameters, microbial diversity, and metabolic functions, and reveals the importance of crop rotation sequences. These findings could be used to guide decision-making from the microbial perspective for annual crop planting and soil management approaches.

Clinical characteristics of new-onset acute kidney injury in patients with established acute respiratory distress syndrome: A prospective single-center post hoc observational study.

Background: We assessed the incidence and clinical characteristics of acute kidney injury (AKI) in acute respiratory distress syndrome (ARDS) patients and its effect on clinical outcomes. Methods: We conducted a single-center prospective longitudinal study. Patients who met the Berlin definition of ARDS in the medical ICU in China-Japan Friendship Hospital from March 1, 2016, to September 30, 2020, were included. AKI was defined according to the KDIGO clinical practice guidelines. Early and late AKI were defined as AKI occurring within 48 h after ARDS was diagnosed or after 48 h, respectively. Results: Of the 311 ARDS patients, 161 (51.8%) developed AKI after ICU admission. Independent risk factors for AKI in ARDS patients were age (OR 1.027, 95% CI 1.009-1.045), a history of diabetes mellitus (OR 2.110, 95%CI 1.100-4.046) and chronic kidney disease (CKD) (OR 9.328, 95%CI 2.393-36.363), APACHE II score (OR 1.049, 95%CI 1.008-1.092), average lactate level in the first 3 days (OR 1.965, 95%CI 1.287-3.020) and using ECMO support (OR 2.359, 95%CI 1.154-4.824). Early AKI was found in 91 (56.5%) patients and late AKI was found in 70 (43.5%). Early AKI was related to the patient's underlying disease and the severity of hospital admission, while late AKI was related to the application of nephrotoxic drugs. The mortality rate of ARDS combined with AKI was 57.1%, which was independently associated with shock (OR 54.943, 95%CI 9.751-309.573). Conclusion: A significant number of patients with ARDS developed AKI, and the mortality rate for ARDS patients was significantly higher when combined with AKI. Therapeutic drug monitoring should be routinely used to avoid drug toxicity during treatment.

GPR87 promotes renal tubulointerstitial fibrosis by accelerating glycolysis and mitochondrial injury.

Renal tubulointerstitial fibrosis is the hallmark of chronic kidney disease (CKD) and the best predictor of renal survival. However, current treatments for CKD remain extremely limited. Therefore, novel therapeutic targets are urgently needed to either stop or reverse CKD progression. The present study was designed to explore the potential role of GPR87, a member of the G protein-coupled receptors (GPCRs) family, in the pathogenesis of tubulointerstitial fibrosis. It was found that GPR87 was significantly induced in the kidney, especially in tubular areas, from different mouse models of renal fibrosis, including unilateral ureteral obstruction (UUO) nephropathy, aristolochic acid nephropathy, and diabetic nephropathy, respectively. Tubule-specific GPR87 deletion dramatically ameliorated tubulointerstitial fibrosis in UUO mice. Mechanistically, GPR87 accelerated glycolysis and mitochondrial injury by YAP-hexokinase-2 signaling, thereby promoting renal fibrosis. Importantly, the upregulation of GPR87 was also found in the kidney from patients with various CKD, indicating that the induction of GPR87 may be a common feature of human kidney diseases. Collectively, our studies for the first time demonstrate that GPR87 plays a pivotal role in renal fibrosis at least in part by accelerating glycolysis and mitochondrial injury, suggesting that targeting GPR87 may represent a novel therapeutic strategy for patients with CKD.

Intravenous Calcium Alginate Microspheres as Drug Delivery Vehicles in Acute Kidney Injury Treatment.

Acute kidney injury (AKI) is a common and severe problem associated with high morbidity, mortality, and healthcare costs. There are no reliable therapeutic interventions except dialysis that could improve survival, limit injury, or speed up recovery. Thus, it is essential to develop new therapies to treat AKI. Previous studies revealed that histone deacetylase inhibitor (HDACi) could attenuate renal injury and enhance kidney recovery in AKI. However, the hydrophobic nature of HDACi, such as vorinostat (SAHA), requires organic solvents to promote its dissolution, leading to inevitable detrimental effects. Herein, calcium alginate microspheres (CAM) were prepared by the microfluidic method as HDACi carriers to treat AKI by intravenous injection. First, we designed the structure of the microfluidic channel for the fabrication of the PDMS microfluidic chip in which the emulsion state of droplets was analyzed. As the flow rate increases, the continuous phase changed from laminar flow to the dripping pattern in the microfluidic device. Then, the CAM was fabricated by a W/O microfluidic emulsion template and the size of the microspheres was adjusted from 3 to 7 µm by the concentration of alginate and the flow rate of the continuous phase and dispersal phase. The higher degree of cross-linking of sodium alginate with calcium ions would lead to longer drug release time but lower swelling rates. Furthermore, we selected CAM with suitable sizes as the HDACi carrier and delivered the HDACi-loaded CAM to the AKI mice by intravenous tail injection. The in vivo results showed that the HDACi-loaded CAM could effectively reduce the renal regional inflammatory response and attenuate renal injury.

Long-Term Manure Amendment Sustains Black Soil Biodiversity by Mitigating Acidification Induced by Chemical N Fertilization.

The long-term use of chemical N fertilization may have a negative impact upon soil fertility and quality. On the contrary, organic fertilization is considered a sustainable development agricultural strategy. However, the remediation effect of organic fertilization on agroecosystems remains unclear. This study was conducted in a long-term (1979−2020) field experiment to investigate the influence of organic and chemical fertilizers on the soil microbiome assembly processes. The experiment consisted of six treatments: chemical N fertilization (N), double N fertilization (N2), organic fertilization (M), organic and N fertilization (MN), double organic and N fertilization (M2N2), and unfertilized control. The chemical N fertilization (N and N2) treatments significantly decreased soil microbial diversity, as well as soil pH, compared to the Control treatments (p < 0.05). MN and M2N2 treatments increased microbial diversity compared to that of N and N2 treatments. The combination of organic and chemical N fertilizer recovered the decreased microbial diversity to the level of the Control and M treatments, but the application of double organic fertilizer (M2N2) still showed a significantly lower microbial diversity than that of the Control and M treatments. From the results of the microbial community assembly processes, it was found that environmental filtering was induced by N fertilization, while organic fertilization developed a stochastic process and mitigated the role of environmental filtering in the community assembly process. An ecological network analysis showed that the decrease in Acidobacteria in organic fertilization treatments played a key role in mitigating the soil acidification induced by 40-year chemical N fertilization. It indicated that organic fertilizer could mitigate the decrease in soil fertility induced by chemical N fertilization. Higher environmental filtering effects in M2N2 than those in MN treatments suggested that the mitigation effect of organic fertilizer was weakened when double chemical N fertilization was applied in black soils. These results are helpful for a unified understanding of the ecological processes for microbial communities in the development of sustainable agriculture.

Impact of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers on the Inflammatory Response and Viral Clearance in COVID-19 Patients.

Objectives: To evaluate the impact of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) on the inflammatory response and viral clearance in coronavirus disease 2019 (COVID-19) patients. Methods: We included 229 patients with confirmed COVID-19 in a multicenter, retrospective cohort study. Propensity score matching at a ratio of 1:3 was introduced to eliminate potential confounders. Patients were assigned to the ACEI/ARB group (n = 38) or control group (n = 114) according to whether they were current users of medication. Results: Compared to the control group, patients in the ACEI/ARB group had lower levels of plasma IL-1ß [(6.20 ± 0.38) vs. (9.30 ± 0.31) pg/ml, P = 0.020], IL-6 [(31.86 ± 4.07) vs. (48.47 ± 3.11) pg/ml, P = 0.041], IL-8 [(34.66 ± 1.90) vs. (47.93 ± 1.21) pg/ml, P = 0.027], and TNF-α [(6.11 ± 0.88) vs. (12.73 ± 0.26) pg/ml, P < 0.01]. Current users of ACEIs/ARBs seemed to have a higher rate of vasoconstrictive agents (20 vs. 6%, P < 0.01) than the control group. Decreased lymphocyte counts [(0.76 ± 0.31) vs. (1.01 ± 0.45)*109/L, P = 0.027] and elevated plasma levels of IL-10 [(9.91 ± 0.42) vs. (5.26 ± 0.21) pg/ml, P = 0.012] were also important discoveries in the ACEI/ARB group. Patients in the ACEI/ARB group had a prolonged duration of viral shedding [(24 ± 5) vs. (18 ± 5) days, P = 0.034] and increased length of hospitalization [(24 ± 11) vs. (15 ± 7) days, P < 0.01]. These trends were similar in patients with hypertension. Conclusions: Our findings did not provide evidence for a significant association between ACEI/ARB treatment and COVID-19 mortality. ACEIs/ARBs might decrease proinflammatory cytokines, but antiviral treatment should be enforced, and hemodynamics should be monitored closely. Since the limited influence on the ACEI/ARB treatment, they should not be withdrawn if there was no formal contraindication.

CLEC14A protects against podocyte injury in mice with adriamycin nephropathy.

Podocyte injury is a major determinant of focal segmental glomerular sclerosis (FSGS) and the identification of potential therapeutic targets for preventing podocyte injury has clinical importance for the treatment of FSGS. CLEC14A is a single-pass transmembrane glycoprotein belonging to the vascular expressed C-type lectin family. CLEC14A is found to be expressed in vascular endothelial cells during embryogenesis and is also implicated in tumor angiogenesis. However, the current understanding of the biological functions of CLEC14A in podocyte is very limited. In this study, we found that CLEC14A was expressed in podocyte and protected against podocyte injury in mice with Adriamycin (ADR)-induced FSGS. First, we observed that CLEC14A was downregulated in mice with ADR nephropathy and renal biopsies from individuals with FSGS and other forms of podocytopathies. Moreover, CLEC14A deficiency exacerbated podocyte injury and proteinuria in mice with ADR nephropathy accompanied by enhanced inflammatory cell infiltration and inflammatory responses. In vitro, overexpression of CLEC14A in podocyte had pleiotropic protective actions, including anti-inflammatory and anti-apoptosis effects. Mechanistically, CLEC14A inhibited high-mobility group box 1 protein (HMGB1) release, at least in part by directly binding HMGB1, and suppressed HMGB1-mediated signaling, including NF-κB signaling and early growth response protein 1 (EGR1) signaling. Taken together, our findings provide new insights into the pivotal role of CLEC14A in maintaining podocyte function, indicating that CLEC14A may be an innovative therapeutic target in FSGS.

Efficient Nitrogen Fixation to Ammonia through Integration of Plasma Oxidation with Electrocatalytic Reduction.

Present one-step N2 fixation is impeded by tough activation of the N≡N bond and low selectivity to NH3 . Here we report fixation of N2 -to-NH3 can be decoupled to a two-step process with one problem effectively solved in each step, including: 1) facile activation of N2 to NOx - by a non-thermal plasma technique, and 2) highly selective conversion of NOx - to NH3 by electrocatalytic reduction. Importantly, this process uses air and water as low-cost raw materials for scalable ammonia production under ambient conditions. For NOx - reduction to NH3 , we present a surface boron-rich core-shell nickel boride electrocatalyst. The surface boron-rich feature is the key to boosting activity, selectivity, and stability via enhanced NOx - adsorption, and suppression of hydrogen evolution and surface Ni oxidation. A significant ammonia production of 198.3 µmol cm-2 h-1 was achieved, together with nearly 100 % Faradaic efficiency.

Graphene oxide affects growth and physiological indexes in Larix olgensis seedlings and the soil properties of Haplic Cambisols in Northeast China.

Changbai larch (Larix olgensis A. Henry) seedlings growing in a Haplic Cambisol and receiving 0 (Ck), 25, 50, 100, 250, or 500 mg L-1 graphene oxide (GO) were incubated for 30, 40, or 50 days, and the effects of applying GO on the growth and physiological characteristics of the seedlings and soil chemical properties and enzyme activities were investigated. The superoxide anion (except for 25 mg L-1 at 40 days and 50 mg L-1 at 50 days) and hydrogen peroxide contents of the leaves increased at 25-100 mg L-1 GO; however, superoxide dismutase (SOD) and peroxidase (POD) (except for 100 mg L-1 at 50 days) activities, soluble protein (except for 100 mg L-1 at 30 and 40 days), proline (except for 100 mg L-1 at 50 days), as well as seedling biomass (except for stems at 25-100 mg L-1, and leaves and roots at 50-100 mg L-1 for 30 days) all decreased. However, when the seedlings were exposed to 250-500 mg L-1 GO, especially at 40 and 50 days, these trends for tree growth and physiological parameters were reversed, suggesting the beneficial effect of GO at high concentrations on the seedlings. GO decreased the organic matter, alkali-hydrolyzale nitrogen, available phosphorus, and potassium contents of the soil at 40 and 50 days (except for available phosphorus at 50 days), as well as the acid phosphatase, urease (except for 30 days), dehydrogenase, and catalase activities (except for 30 and 40 days); thus, GO may inhibit nitrogen and phosphorus cycling in Haplic Cambisols (except for nitrogen at 30 days).

Comparative metabolomics of two saline-alkali tolerant plants Suaeda glauca and Puccinellia tenuiflora based on GC-MS platform.

Suaeda glauca and Puccinellia tenuiflora are two important saline-alkali tolerant plants that can improve the soil properties. For exploring the different tolerance mechanisms between them, GC-MS-based metabolomics was used to comprehensively evaluate the primary metabolites differences, a total of 51 different metabolites were present in different quantities. The identified compounds were mainly 11 sugars, 7 amino acids, 5 alcohols and 18 organic acids; they play an important role in responding to the saline-alkali stress and distinguish between S. glauca and P. tenuiflora. All identified metabolites classes showed similar trend to largely accumulate in P. tenuiflora roots and S. glauca shoots, this reveals that the two plants used different physiological strategies to cope with saline-alkali stress.

Acute Kidney Injury in Patients with the Coronavirus Disease 2019: A Multicenter Study.

INTRODUCTION: Severe acute respiratory viral infections are frequency accompanied by multiple organ dysfunction, including acute kidney injury (AKI). In December 2019, the coronavirus disease 2019 (COVID-19) outbreak began in Wuhan, Hubei Province, China, and rapidly spread worldwide. While diffuse alveolar damage and acute respiratory failure are the main features of COVID-19, other organs may be involved, and the incidence of AKI is not well described. We assessed the incidence and clinical characteristics of AKI in patients with laboratory-confirmed COVID-19 and its effects on clinical outcomes. METHODS: We conducted a multicenter, retrospective, observational study of patients with COVID-19 admitted to two general hospitals in Wuhan from 5 January 2020 to 21 March 2020. Demographic data and information on organ dysfunction were collected daily. AKI was defined according to the KDIGO clinical practice guidelines. Early and late AKI were defined as AKI occurring within 72 h after admission or after 72 h, respectively. RESULTS: Of the 116 patients, AKI developed in 21 (18.1%) patients. Among them, early and late AKI were found in 13 (11.2%) and 8 (6.9%) patients, respectively. Compared with patients without AKI, patients with AKI had more severe organ dysfunction, as indicated by a higher level of disease severity status, higher sequential organ failure assessment (SOFA) score on admission, an increased prevalence of shock, and a higher level of respiratory support. Patients with AKI had a higher SOFA score on admission (4.5 ± 2.1 vs. 2.8 ± 1.4, OR 1.498, 95% CI 1.047-2.143 ) and greater hospital mortality (57.1% vs. 12.6%, OR 3.998, 95% CI 1.088-14.613) than patients without AKI in both the univariate and multivariate analyses. Patients with late AKI, but not those with early AKI, had a significantly prolonged length of stay (19.6 vs. 9.6 days, p = 0.015). CONCLUSION: Our findings show that admission SOFA score was an independent risk factor for AKI in COVID-19 patients, and patients with AKI had higher in-hospital mortality. Moreover, AKI development after 72 h of admission was related to prolonged hospitalization time.

Histone Deacetylase Inhibitor-loaded Calcium Alginate Microspheres for Acute Kidney Injury Treatment.

The protective effects of histone deacetylase (HDAC) inhibitors were highlighted in the treatment of kidney diseases, especially acute kidney injury (AKI). However, the currently available HDAC inhibitor cannot be delivered to the kidney properly because of its poor solubility in aqueous solutions. Therefore, calcium alginate (Ca-ALG) microspheres were proposed as microcarriers for the delivery of HDAC inhibitors in this study. First, Ca-ALG microspheres with high sphericity were obtained by a single-emulsion microfluidic strategy. Then, we selected suitable Ca-ALG microspheres for HDAC inhibitor loading by analyzing the swelling ratio and the release property using different parameters. Besides, thermal stimulation will change the drug release property of Ca-ALG microspheres in in vitro experiments. Furthermore, the HDAC inhibitor-loaded microspheres were delivered to the kidney by renal subcapsular injection for evaluating the treatment effects in mice with ischemia-reperfusion-induced AKI. The in vivo results showed that the HDAC inhibitor-loaded Ca-ALG microspheres could effectively reduce the renal regional inflammatory response and macrophage infiltration. Taken together, we proposed a promising therapy with an effective kidney-targeted drug delivery for the treatment of AKI.