LncRNA cis- and trans-regulation provides new insight into drought stress responses in wild barley.

Drought is one of the most common abiotic stresses that affect barley productivity. Long noncoding RNA (lncRNA) has been reported to be widely involved in abiotic stress, however, its function in the drought stress response in wild barley remains unclear. In this study, RNA sequencing was performed to identify differentially expressed lncRNAs (DElncRNA) among two wild barley and two cultivated barley genotypes. Then, the cis-regulatory networks were according to the chromosome position and the expression level correction. The GO annotation indicates that these cis-target genes are mainly involved in "ion transport transporter activity" and "metal ion transport transporter activity". Through weighted gene co-expression network analysis (WGCNA), 10 drought-related modules were identified to contract trans-regulatory networks. The KEGG annotation demonstrated that these trans-target genes were enriched for photosynthetic physiology, brassinosteroid biosynthesis, and flavonoid metabolism. In addition, we constructed the lncRNA-mediated ceRNA regulatory network by predicting the microRNA response elements (MREs). Furthermore, the expressions of lncRNAs were verified by RT-qPCR. Functional verification of a candidate lncRNA, MSTRG.32128, demonstrated its positive role in drought response and root growth and development regulation. Hormone content analysis provided insights into the regulatory mechanisms of MSTRG.32128 in root development, revealing its involvement in auxin and ethylene signal transduction pathways. These findings advance our understanding of lncRNA-mediated regulatory mechanisms in barley under drought stress. Our results will provide new insights into the functions of lncRNAs in barley responding to drought stress.

Novel chymotrypsin C (CTRC) variants from real-world genetic testing of pediatric chronic pancreatitis cases.

BACKGROUND: Chymotrypsin C (CTRC) protects the pancreas against unwanted intrapancreatic trypsin activity through degradation of trypsinogen. Loss-of-function CTRC variants increase the risk for chronic pancreatitis (CP). The aim of the present study was to characterize novel CTRC variants found during genetic testing of CP cases at a pediatric pancreatitis center. METHODS: We used next-generation sequencing to screen patients. We analyzed the functional effects of CTRC variants in HEK 293T cells and using purified enzymes. RESULTS: In 5 separate cases, we detected 5 novel heterozygous CTRC variants: c.407C>T (p.Thr136Ile), c.550G>A (p.Ala184Thr), c.627Cdup (p.Ser210Leufs∗?, where the naming indicates a frame shift with no stop codon), c.628T>C (p.Ser210Pro), and c.779A>G (p.Asp260Gly). Functional studies revealed that with the exception of p.Ser210Leufs∗?, the CTRC variants were secreted normally from transfected cells. Enzyme activity of purified variants p.Thr136Ile, p.Ala184Thr, and p.Asp260Gly was similar to that of wild-type CTRC, whereas variant p.Ser210Pro was inactive. The frame-shift variant p.Ser210Leufs∗? was not secreted but accumulated intracellularly, and induced endoplasmic reticulum stress, as judged by elevated mRNA levels of HSPA5 and DDIT3, and increased mRNA splicing of XBP1. CONCLUSIONS: CTRC variants p.Ser210Pro and p.Ser210Leufs∗? abolish CTRC function and should be classified as pathogenic. Mechanistically, variant p.Ser210Pro directly affects the amino acid at the bottom of the substrate-binding pocket while the frame-shift variant promotes misfolding and thereby blocks enzyme secretion. Importantly, 3 of the 5 novel CTRC variants proved to be benign, indicating that functional analysis is indispensable for reliable determination of pathogenicity and the correct interpretation of genetic test results.

The Role of Pancreatitis Risk Genes in Endocrine Insufficiency Development After Acute Pancreatitis in Children.

BACKGROUND & AIMS: Acute pancreatitis (AP) is increasingly recognized as a risk factor for diabetes mellitus (DM). We aimed to study the association of pancreatitis genes with pancreatic endocrine insufficiency (pre-DM and DM) development post-AP in children. METHODS: This was an observational cohort study that enrolled subjects ≤21 years with their first episode of AP and followed them for 12 months for the development of pancreatic endocrine insufficiency. Pancreatitis risk genes (CASR, CEL, CFTR, CLDN2, CPA1, CTRC, PRSS1, SBDS, SPINK1, and UBR1) were sequenced. A genetic risk score was derived from all genes with univariable P < .15. RESULTS: A total 120 subjects with AP were genotyped. Sixty-three subjects (52.5%) had at least 1 reportable variant identified. For modeling the development of pancreatic endocrine insufficiency at 1 year, 6 were excluded (2 with DM at baseline, 3 with total pancreatectomy, and 1 death). From this group of 114, 95 remained normoglycemic and 19 (17%) developed endocrine insufficiency (4 DM, 15 pre-DM). Severe AP (58% vs 20%; P = .001) and at least 1 gene affected (79% vs 47%; P = .01) were enriched among the endocrine-insufficient group. Those with versus without endocrine insufficiency were similar in age, sex, race, ethnicity, body mass index, and AP recurrence. A model for pre-DM/DM development included AP severity (odds ratio, 5.17 [1.66-16.15]; P = .005) and genetic risk score (odds ratio, 4.89 [1.83-13.08]; P = .002) and had an area under the curve of 0.74. CONCLUSIONS: In this cohort of children with AP, pancreatitis risk genes and AP disease severity were associated with pre-DM or DM development post-AP.

Inter-provincial embodied carbon emission space and industrial transfer paths in China.

To bolster the dual-circulation development model and green economy, this study delves into the spatiotemporal dynamics of implied carbon transfer in China's inter-provincial and inter-industrial trade, emphasizing its significance for the "dual carbon" objectives. Utilizing multi-regional input-output data from 2012, 2015, and 2017, we employed the multi-region input-output model to gauge embodied carbon transfers across 31 provinces and 28 industries. The Structural Decomposition Analysis (SDA) model further decomposed the growth of trade-related carbon emissions. Key findings include: (1) The electricity and thermal power sectors dominate carbon transfers, with secondary industries seeing rapid growth; (2) Northern provinces significantly outweigh southern ones in carbon transfers and the main direction of it is towards affluent southern coastal regions; (3) Scale effect plays a pivotal role in these transfers. Conclusively, it is crucial for regulatory authorities to rationally formulate region-specific emission policies for inter-regional coordination, and future studies can focus on industrial and spatial clustering effects.

Analysis of chitinase gene family in barley and function study of HvChi22 involved in drought tolerance.

BACKGROUND: Chitinase (Chi) is a pathogenesis-related protein, also reported to play an important role in plant responses to abiotic stress. However, its role in response to abiotic stress in barley is still unclear. RESULTS: In this study, a total of 61 Chi gene family members were identified from the whole genome of wild barley EC_S1. Phylogenetic analysis suggested that these family genes were divided into five groups. Among these genes, four pairs of collinearity genes were discovered. Besides, abundant cis-regulatory elements, including drought response element and abscisic acid response element were identified in the promoter regions of HvChi gene family members. The expression profiles revealed that most HvChi family members were significantly up-regulated under drought stress, which was also validated by RT-qPCR measurements. To further explore the role of Chi under drought stress, HvChi22 was overexpressed in Arabidopsis. Compared to wild-type plants, overexpression of HvChi22 enhanced drought tolerance by increasing the activity of oxidative protective enzymes, which caused less MDA accumulation. CONCLUSION: Our study improved the understanding of the Chi gene family under drought stress in barley, and provided a theoretical basis for crop improvement strategies to address the challenges posed by changing environmental conditions.

Drought-induced assembly of rhizosphere mycobiomes shows beneficial effects on plant growth.

Beneficial interactions between plants and rhizosphere fungi can enhance plant adaptability during drought stress. However, harnessing these interactions will require an in-depth understanding of the response of fungal community assembly to drought. Herein, by using different varieties of wheat plants, we analyzed the drought-induced changes in fungal community assembly in rhizosphere and bulk soil. We demonstrated that drought significantly altered the fungal communities, with the contribution of species richness to community beta diversity increased in both rhizosphere and bulk soil compartments during drought stress. The stochastic processes dominated fungal community assembly, but the relative importance of deterministic processes, mainly homogeneous selection, increased in the drought-stressed rhizosphere. Drought induced an increase in the relative abundance of generalists in the rhizosphere, as opposed to specialists, and the top 10 abundant taxa that enriched under drought conditions were predominantly generalists. Notably, the most abundant drought-enriched taxon in rhizosphere was a generalist, and the corresponding Chaetomium strain was found capable of improving root length and activating ABA signaling in wheat plants through culture-based experiment. Together, these findings provide evidence that host plants exert a strong influence on rhizospheric fungal community assembly during stress and suggest the fungal communities that have experienced drought have the potential to confer fitness advantages to the host plants. IMPORTANCE: We have presented a framework to integrate the shifts in community assembly processes with plant-soil feedback during drought stress. We found that environmental filtering and host plant selection exert influence on the rhizospheric fungal community assembly, and the re-assembled community has great potential to alleviate plant drought stress. Our study proposes that future research should incorporate ecology with plant, microbiome, and molecular approaches to effectively harness the rhizospheric microbiome for enhancing the resilience of crop production to drought.

Heat shock protein HvHSP16.9 from wild barley enhances tolerance to salt stress.

Heat shock proteins (HSPs) are known to play a crucial role in the response of plants to environmental stress, particularly heat stress. Nevertheless, the function of HSPs in salt stress tolerance in plants, especially in barley, remains largely unexplored. Here, we aimed to investigate and compare the salt tolerance mechanisms between wild barley EC_S1 and cultivated barley RGT Planet through a comprehensive analysis of physiological parameters and transcriptomic profiles. Results demonstrated that the number of differentially expressed genes (DEGs) in EC_S1 was significantly higher than in RGT Planet, indicating that wild barley gene regulation is more adaptive to salt stress. KEGG enrichment analysis revealed that DEGs were mainly enriched in the processes of photosynthesis, plant hormone signal transduction, and reactive oxygen species metabolism. Furthermore, the application of weighted gene correlation network analysis (WGCNA) enabled the identification of a set of key genes, including small heat shock protein (sHSP), Calmodulin-like proteins (CML), and protein phosphatases 2C (PP2C). Subsequently, a novel sHSP gene, HvHSP16.9 encoding a protein of 16.9 kDa, was cloned from wild barley, and its role in plant response to salt stress was elucidated. In Arabidopsis, overexpression of HvHSP16.9 increased the salt tolerance. Meanwhile, barley stripe mosaic virus-induced gene silencing (BSMV-VIGS) of HvHSP16.9 significantly reduced the salt tolerance in wild barley. Overall, this study offers a new theoretical framework for comprehending the tolerance and adaptation mechanisms of wild barley under salt stress. It provides valuable insights into the salt tolerance function of HSP, and identifies new candidate genes for enhancing cultivated barley varieties. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-024-01455-4.

Relationship between socioeconomic status and hypertension incidence among adults in southwest China: a population-based cohort study.

PURPOSE: To investigate the correlation between socioeconomic status (SES) and the incidence of hypertension among adults aged 18 or above in southwest China. METHODS: A multistage proportional stratified cluster sampling method was employed to recruited 9280 adult residents from 12 counties in southwest China, with all participants in the cohort tracked from 2016 to 2020. The questionnaire survey gathered information on demographics, lifestyle habits, and household income. The physical exam recorded height, weight, and blood pressure. Biochemical tests measured cholesterol levels. The chi-square test was employed to assess the statistical differences among categorical variables, while the Cox proportional hazards regression model was applied to evaluate the association between socioeconomic status (SES) and the incidence of hypertension. RESULTS: The finally effective sample size for the cohort study was 3546 participants, after excluding 5734 people who met the exclusion criteria. Adults in the highest household income group had a significantly lower risk of hypertension compared to those in the lowest income group (HR = 0.636, 95% CI: 0.478-0.845). Besides, when compared to individuals in the illiterate population, the risk of hypertension among adults with elementary school, junior high school, senior high school and associate degree educational level decreased respectively by 34.4% (HR = 0.656, 95%CI: 0.533-0.807), 44.9% (HR = 0.551, 95%CI: 0.436-0.697), 44.9% (HR = 0.551, 95%CI: 0.405-0.750), 46.1% (HR = 0.539, 95%CI: 0. 340-0.854). After conducting a thorough analysis of socioeconomic status, compared with individuals with a score of 6 or less, the risk of hypertension in participants with scores of 8, 10, 11, 12, and greater than 12 decreased respectively by 23.9% (HR = 0.761, 95%CI: 0.598-0.969), 29.7% (HR = 0.703, 95%CI: 0.538-0.919), 34.0% (HR = 0.660, 95%CI: 0.492-0.885), 34.3% (HR = 0.657, 95%CI: 0.447-0.967), 43.9% (HR = 0.561, 95%CI: 0.409-0.769). CONCLUSION: The findings indicate a negative correlation between socioeconomic status and hypertension incidence among adults in southwest China, suggesting that individuals with higher socioeconomic status are less likely to develop hypertension.

The impact of heteroaggregation between nZVI and SNPs on the co-transport of Cd(II) in saturated sand columns.

This study investigated the co-transport behaviors of nano zero-valent iron (nZVI) and Cd(II) in the presence of soil nanoparticles (SNPs) under various SNPs/nZVI mass ratios. It was illustrated that the mobility of colloidal Cd(II) was highly dependent on the nZVI-SNPs heteroaggregation behavior. In the case of 40 mg/L nZVI with SNPs/nZVI mass ratios > 1, the formation of stable SNPs-nZVI heteroaggregates with hydrodynamic diameters (Dh) < 500 nm facilitated the nZVI and colloidal Cd(II) transport at their effluent mass recoveries of 34.76-37.82 % and 9.81-17.17 %, respectively. However, in the case of 100 mg/L nZVI with SNPs/nZVI mass ratios of 0.4-2, the interception of nZVI-SNPs heteroaggregates with Dh > 1500 nm by quartz sands led to almost complete retention of nZVI and colloidal Cd(II) in the columns. Combined with analytical results of zeta potentials and XRD spectrum, it was revealed that the Cd(II) ions could accelerate nZVI corrosion. The positively charged Fe3O4 and γ-FeOOH on corroded nZVI surface could facilitate the heteroaggregation of nZVI-SNPs by the patch-charge attraction, which further reduced the environmental risk of colloidal Cd(II) transport. These findings revealed the important effects of heteroaggregation between nZVI and SNPs on the transport risk of Cd(II) in groundwater.

Critical care therapies pre- and post-heart transplant and their impact: Analysis from the Pediatric Cardiac Critical Care Consortium.

BACKGROUND: Few studies highlighting the critical care management of patients after heart HTx (HTx) have been published to date. This analysis provides a contemporary representation of pre- and post-HTx critical care in various patient cohorts and outlines the impact of intensive care unit (ICU) therapies on outcomes. METHODS: Data from PC4 Collaborative Registry were analyzed for pediatric patients undergoing HTx between August 2014 and April 2022. RESULTS: A total of 1877 HTx in 1857 patients were reported from 42 centers; 56.5% had congenital heart disease (CHD). Patients with CHD were younger, smaller, more likely male, White race, and publicly insured. CHD patients had higher need for catheterization, increased likelihood of inotropic support and mechanical ventilation and lower VAD rates. Their operative courses were significant for longer bypass and cross-clamp times. Postoperatively, CHD patients required more CPR , utilized more ICU therapies and had higher hospital mortality (7.8% vs. 1.8% for non-CHD patients, p<0.0001). Longer cardiopulmonary bypass, longer deep hypothermic circulatory arrest times and delayed sternal closure were independent risk factors for hospital mortality. Lastly, center transplant volume but not surgical volume was associated with transplant outcomes. CONCLUSIONS: A diagnosis of CHD before HTx is associated with a greater use of ICU-specific therapies compared non-CHD cohort. Operative factors, particularly in patients with CHD, are independently associated with higher hospital mortality as was low transplant volume at the center. The study provides basis for further investigating ICU and operative factors that can be modified to improve transplant outcomes.

Colonization of root endophytic fungus Serendipita indica improves drought tolerance of Pinus taeda seedlings by regulating metabolome and proteome.

Pinus taeda is an important forest tree species for plantations because of its rapid growth and high yield of oleoresins. Although P. taeda plantations distribute in warm and wet southern China, drought, sometime serious and long time, often occurs in the region. To explore drought tolerance of P. taeda and usage of beneficial microorganisms, P. taeda seedlings were planted in pots and were inoculated with root endophytic fungus Serendipita indica and finally were treated with drought stress for 53 d. Metabolome and proteome of their needles were analyzed. The results showed that S. indica inoculation of P. taeda seedlings under drought stress caused great changes in levels of some metabolites in their needles, especially some flavonoids and organic acids. Among them, the levels of eriocitrin, trans-aconitic acid, vitamin C, uric acid, alpha-ketoglutaric acid, vitamin A, stachydrine, coumalic acid, itaconic acid, calceolarioside B, 2-oxoglutaric acid, and citric acid were upregulated more than three times in inoculated seedlings under drought stress, compared to those of non-inoculated seedlings under drought stress. KEGG analysis showed that some pathways were enriched in inoculated seedlings under drought stress, such as flavonoid biosynthesis, ascorbate and aldarate metabolism, C5-branched dibasic acid metabolism. Proteome analysis revealed some specific differential proteins. Two proteins, namely, H9X056 and H9VDW5, only appeared in the needles of inoculated seedlings under drought stress. The protein H9VNE7 was upregulated more than 11.0 times as that of non-inoculated seedlings under drought stress. In addition, S. indica inoculation increased enrichment of water deficient-inducible proteins (such as LP3-1, LP3-2, LP3-3, and dehydrins) and those involved in ribosomal structures (such as A0A385JF23). Meanwhile, under drought stress, the inoculation caused great changes in biosynthesis and metabolism pathways, mainly including phenylpropanoid biosynthesis, cutin, suberine and wax biosynthesis, and 2-oxocarboxylic acid metabolism. In addition, there were positive relationships between accumulation of some metabolites and enrichment of proteins in P. taeda under drought stress. Altogether, our results showed great changes in metabolome and proteome in inoculated seedlings under drought stress and provided a guideline to further study functions of metabolites and proteins, especially those related to drought stress.

Loop PDE of viral capsid protein is involved in immune escape of the emerging novel variant infectious bursal disease virus.

Infectious bursa disease (IBD) is an acute, highly contactable, lethal, immunosuppressive infectious disease caused by the Infectious bursa disease virus (IBDV). Currently, the emerged novel variant IBDV (nVarIBDV) and the sustainedly prevalent very virulent IBDV (vvIBDV) are the two most prevalent strains of IBDV in China. The antigenic properties of the two prevalent strains differed significantly, which led to the escape of nVarIBDV from the immune protection provided by the existing vvIBDV vaccine. However, the molecular basis of the nVarIBDV immune escape remains unclear. In this study, we demonstrated, for the first time, that residues 252, 254, and 256 in the PDE of VP2 are involved in the immune escape of the emerging nVarIBDV. Firstly, the IFA-mediated antigen-antibody affinity assay showed that PBC and PDE of VP2 could affect the affinity of vvIBDV antiserum to VP2, of which PDE was more significant. The key amino acids of PDE influencing the antigen-antibody affinity were also identified, with G254N being the most significant, followed by V252I and I256V. Then the mutated virus with point or combined mutations was rescued by reverse genetics. it was further demonstrated that mutations of V252I, G254N, and I256V in PDE could individually or collaboratively reduce antigen-antibody affinity and interfere with antiserum neutralization, with G254N being the most significant. This study revealed the reasons for the widespread prevalence of nVarIBDV in immunized chicken flocks and provided innovative ideas for designing novel vaccines that match the antigen of the epidemic strain.

Targeted delivery of NO donor and ROS scavenger for synergistic treatment of rheumatoid arthritis.

Rheumatoid arthritis (RA) is characterized by high level of reactive oxygen species (ROS) and proinflammatory cytokines, which facilitate the activation of the inflammatory signaling such as NF-κB pathway and exacerbate the development of inflammation. Herein, we designed a nanodrug by encapsulating the NO donor S-nitrosoglutathione (GSNO) into an emulsion and coating the surface with a polydopamine (PDA) layer to yield GSNO@PDA, which simultaneously scavenged the extra ROS and suppressed NF-κB signaling for potent RA treatment. To enhance the cellular uptake and NO generation efficiency, dextran sulfate (DS) and Cu2+ were anchored on the surface of GSNO@PDA to obtain the final formulation GSNO@PDA@DS. Our results demonstrated that GSNO@PDA@DS were successfully prepared and the modification of DS effectively boosted the cellular uptake of GSNO@PDA@DS. Moreover, GSNO@PDA@DS lowered cellular ROS and elevated intracellular NO, resulting in a decrease of M1 phenotype, inhibition of NF-κB pathway and down-regulation of proinflammatory cytokine tumor necrosis factor-α (TNF-α). Further in vivo studies confirmed that GSNO@PDA@DS significantly relieved symptoms and bone erosion by regulating the microenvironment of RA, highlighting the potential of GSNO@PDA@DS for RA therapy through ROS scavenging and NO-mediated suppression of inflammatory signaling.

Enhanced efficiencies on purifying acid mine drainage in constructed wetlands based on synergistic adsorption of attapulgite-soda residue composites and microbial sulfate reduction.

Constructed wetlands (CWs) are a promising approach for treating acid mine drainage (AMD). However, the extreme acidity and high loads of heavy metals in AMD can easily lead to the collapse of CWs without proper pre-treatment. Therefore, it is considered essential to maintain efficient and stable performance for AMD treatment in CWs. In this study, pre-prepared attapulgite-soda residue (ASR) composites were used to improve the substrate of CWs. Compared with CWs filled with gravel (CWs-G), the removal efficiencies of sulfate and Fe, Mn, Cu, Zn Cd and Pb in CWs filled with ASR composites (CWs-ASR) were increased by 30% and 10-70%, respectively. These metals were mainly retained in the substrate in stable forms, such as carbonate-, Fe/Mn (oxide)hydroxide-, and sulfide-bound forms. Additionally, higher levels of photosynthetic pigments and antioxidant enzyme activities in plants, along with a richer microbial community, were observed in CWs-ASR than in CWs-G. The application of ASR composites alleviated the adverse effects of AMD stresses on wetland plants and microorganisms. In return, the increased bacteria abundance, particularly SRB genera (e.g., Thermodesulfovibrionia and Desulfobacca), promoted the formation of metal sulfides, enabling the saturated ASR adsorbed with metals to regenerate and continuously capture heavy metals. The synergistic adsorption of ASR composites and microbial sulfate reduction maintained the stable and efficient operation of CWs. This study contributes to the resource utilization of industrial alkaline by-products and promotes the breakthrough of new techniques for low-cost and passive treatment systems such as CWs.

LaMYC7, a positive regulator of linalool and caryophyllene biosynthesis, confers plant resistance to Pseudomonas syringae.

Linalool and caryophyllene are the main monoterpene and sesquiterpene compounds in lavender; however, the genes regulating their biosynthesis still remain many unknowns. Here, we identified LaMYC7, a positive regulator of linalool and caryophyllene biosynthesis, confers plant resistance to Pseudomonas syringae. LaMYC7 was highly expressed in glandular trichomes, and LaMYC7 overexpression could significantly increase the linalool and caryophyllene contents and reduce susceptibility to P. syringae in Nicotiana. In addition, the linalool possessed antimicrobial activity against P. syringae growth and acted dose-dependently. Further analysis demonstrated that LaMYC7 directly bound to the promoter region of LaTPS76, which encodes the terpene synthase (TPS) for caryophyllene biosynthesis, and that LaTPS76 was highly expressed in glandular trichomes. Notably, the LaMYC7 promoter contained hormone and stress-responsive regulatory elements and responded to various treatments, including ultraviolet, low temperature, salt, drought, methyl jasmonate, and P. syringae infection treatments. Under these treatments, the changes in the linalool and caryophyllene contents were similar to those in LaMYC7 transcript abundance. Based on the results, LaMYC7 could respond to P. syringae infection in addition to being involved in linalool and caryophyllene biosynthesis. Thus, the MYC transcription factor gene LaMYC7 can be used in the breeding of high-yielding linalool and caryophyllene lavender varieties with pathogen resistance.

Mechanical Ventilation and Outcomes of Children Who Undergo Ventricular Assist Device Placement: 2014-2020 Linked Analysis From the Advanced Cardiac Therapies Improving Outcomes Network and Pediatric Cardiac Critical Care Consortium Registries.

OBJECTIVES: Placement of a ventricular assist device (VAD) improves outcomes in children with advanced heart failure, but adverse events remain important consequences. Preoperative mechanical ventilation (MV) increases mortality, but it is unknown what impact prolonged postoperative MV has. DESIGN: Advanced Cardiac Therapies Improving Outcomes Network (ACTION) and Pediatric Cardiac Critical Care Consortium (PC 4 ) registries were used to identify and link children with initial VAD placement admitted to the cardiac ICU (CICU) from August 2014 to July 2020. Demographics, cardiac diagnosis, preoperative and postoperative CICU courses, and outcomes were compiled. Univariable and multivariable statistics assessed association of patient factors with prolonged postoperative MV. Multivariable logistic regression sought independent associations with outcomes. SETTING: Thirty-five pediatric CICUs across the United States and Canada. PATIENTS: Children on VADs included in both registries. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Two hundred forty-eight ACTION subjects were linked to a matching patient in PC 4 . Median (interquartile) age 7.7 years (1.5-15.5 yr), weight 21.3 kg (9.1-58 kg), and 56% male. Primary diagnosis was congenital heart disease (CHD) in 35%. Pre-VAD explanatory variables independently associated with prolonged postoperative MV included: age (incidence rate ratio [IRR], 0.95; 95% CI, 0.93-0.96; p < 0.01); preoperative MV within 48 hours (IRR, 2.76; 95% CI, 1.59-4.79; p < 0.01), 2-7 days (IRR, 1.82; 95% CI, 1.15-2.89; p = 0.011), and greater than 7 days before VAD implant (IRR, 2.35; 95% CI, 1.62-3.4; p < 0.01); and CHD (IRR, 1.96; 95% CI, 1.48-2.59; p < 0.01). Each additional day of postoperative MV was associated with greater odds of mortality (odds ratio [OR], 1.09 per day; p < 0.01) in the full cohort. We identified an associated greater odds of mortality in the 102 patients with intracorporeal devices (OR, 1.24; 95% CI, 1.04-1.48; p = 0.014), but not paracorporeal devices (77 patients; OR, 1.04; 95% CI, 0.99-1.09; p = 0.115). CONCLUSIONS: Prolonged MV after VAD placement is associated with greater odds of mortality in intracorporeal devices, which may indicate inadequacy of cardiopulmonary support in this group. This linkage provides a platform for future analyses in this population.

Epidemiology of Postoperative Junctional Ectopic Tachycardia in Infants Undergoing Cardiac Surgery.

BACKGROUND: Junctional ectopic tachycardia (JET) complicates congenital heart surgery in 2% to 8.3% of cases. JET is associated with postoperative morbidity in single-center studies. We used the Pediatric Cardiac Critical Care Consortium data registry to provide a multicenter epidemiologic description of treated JET. METHODS: This is a retrospective study (February 2019-August 2022) of patients with treated JET. Inclusion criteria were (1) <12 months old at the index operation, and (2) treated for JET <72 hours after surgery. Diagnosis was defined by receiving treatment (pacing, cooling, and medications). A multilevel logistic regression analysis with hospital random effect identified JET risk factors. Impact of JET on outcomes was estimated by margins/attributable risk analysis using previous risk-adjustment models. RESULTS: Among 24,073 patients from 63 centers, 1436 (6.0%) were treated for JET with significant center variability (0% to 17.9%). Median time to onset was 3.4 hours, with 34% present on admission. Median duration was 2 days (interquartile range, 1-4 days). Tetralogy of Fallot, atrioventricular canal, and ventricular septal defect repair represented >50% of JET. Patient characteristics independently associated with JET included neonatal age, Asian race, cardiopulmonary bypass time, open sternum, and early postoperative inotropic agents. JET was associated with increased risk-adjusted durations of mechanical ventilation (incidence rate ratio, 1.6; 95% CI, 1.5-1.7) and intensive care unit length of stay (incidence rate ratio, 1.3; 95% CI, 1.2-1.3), but not mortality. CONCLUSIONS: JET is treated in 6% of patients with substantial center variability. JET contributes to increased use of postoperative resources. High center variability warrants further study to identify potential modifiable factors that could serve as targets for improvement efforts to ameliorate deleterious outcomes.

Characterization and childhood exposure assessment of toxic heavy metals in household dust under true living conditions from 10 China cities.

Health hazards caused by metal exposure in household dust are concerning environmental health problems. Exposure to toxic metals in household dust imposes unclear but solid health risks, especially for children. In this multicenter cross-sectional study, a total of 250 household dust samples were collected from ten stratified cities in China (Panjin, Shijiazhuang, Qingdao, Lanzhou, Luoyang, Ningbo, Xi'an, Wuxi, Mianyang, Shenzhen) between April 2018 and March 2019. Questionnaire was conducted to gather information on individuals' living environment and health status in real-life situations. Multivariate logistic regression and principal component analysis were conducted to identify risk factors and determine the sources of metals in household dust. The median concentration of five metals in household dust from 10 cities ranged from 0.03 to 73.18 µg/g. Among the five heavy metals, only chromium in household dust of Mianyang was observed significantly both higher in the cold season and from the downwind households. Mercury, cadmium, and chromium were higher in the third-tier cities, with levels of 0.08, 0.30 and 97.28 µg/g, respectively. There were two sources with a contribution rate of 38.3 % and 25.8 %, respectively. Potential risk factors for increased metal concentration include long residence time, close to the motorway, decoration within five years, and purchase of new furniture within one year. Under both moderate and high exposure scenarios, chromium showed the highest level of exposure with 6.77 × 10-4 and 2.28 × 10-3 mg·kg-1·d-1, and arsenic imposed the highest lifetime carcinogenic risk at 1.67 × 10-4 and 3.17 × 10-4, respectively. The finding highlighted the priority to minimize childhood exposure of arsenic from household dust.

CD13 expression affects glioma patient survival and influences key functions of human glioblastoma cell lines in vitro.

CD13 (APN) is an Alanyl-Aminopeptidase with diverse functions. The role of CD13 for gliomas is still unknown. In this study, data of glioma patients obtained by TCGA and CGGA databases were used to evaluate the survival rate and prognostic value of CD13 expression level. Protein expression of CD13 was confirmed by immunofluorescence staining of fresh patient tissues. Eight human glioblastoma cell lines were studied by RT-PCR, Western Blot, immunofluorescence staining and flow cytometry to define CD13 expression. Cell lines with different CD13 expression status were treated with a CD13 inhibitor, bestatin, and examined by MTT, scratch and colony formation assaysas well as by apoptosis assay and Western Blots. Bioinformatics analysis indicated that patients with high expression of CD13 had poor survival and prognosis. Additionally, CD13 protein expression was positively associated with clinical malignant characteristics. Investigated glioblastoma cell lines showed distinct expression levels and subcellular localization of CD13 with intracellular enrichment. Bestatin treatment reduced proliferation, migration and colony formation of glioma cells in a CD13-dependent manner while apoptosis was increased. In summary, CD13 has an impact on glioma patient survival and is important for the main function of specific glioma cells.

Linoleic acid induces human ovarian granulosa cell inflammation and apoptosis through the ER-FOXO1-ROS-NFκB pathway.

Polycystic ovary syndrome (PCOS) is a complex reproductive endocrinological disorder influenced by a combination of genetic and environmental factors. Linoleic acid (LA) is a widely consumed ω-6 polyunsaturated fatty acid, accounting for approximately 80% of daily fatty acid intake. Building upon the prior investigations of our team, which established a connection between LA levels in the follicular fluid and PCOS, this study deeply examined the specific impact of LA using a granulosa cell line. Our findings revealed that LA exerts its influence on granulosa cells (GCs) by binding to the estrogen receptor (ER). Activated ER triggers the transcription of the FOXO1 gene. Reactive oxygen species (ROS)-related oxidative stress (OS) and inflammation occur downstream of LA-induced FOXO1 activation. Increased OS and inflammation ultimately culminate in GC apoptosis. In summary, LA modulates the apoptosis and inflammation phenotypes of GCs through the ER-FOXO1-ROS-NF-κB pathway. Our study provides additional experimental evidence to comprehend the pathophysiology of PCOS and provides novel insights into the dietary management of individuals with PCOS.