DNA damage poses a serious threat to genome integrity and greatly affects growth and development. To maintain genome stability, all organisms have evolved elaborate DNA damage response mechanisms ...including activation of cell cycle checkpoints and DNA repair. Here, we show that the DNA repair protein SNI1, a subunit of the evolutionally conserved SMC5/6 complex, directly links these two processes in Arabidopsis. SNI1 binds to the activation domains of E2F transcription factors, the key regulators of cell cycle progression, and represses their transcriptional activities. In turn, E2Fs activate the expression of SNI1, suggesting that E2Fs and SNI1 form a negative feedback loop. Genetically, overexpression of SNI1 suppresses the phenotypes of E2F-overexpressing plants, and loss of E2F function fully suppresses the sni1 mutant, indicating that SNI1 is necessary and sufficient to inhibit E2Fs. Altogether, our study revealed that SNI1 is a negative regulator of E2Fs and plays dual roles in DNA damage responses by linking cell cycle checkpoint and DNA repair.
Acute kidney injury remains a serious condition with a high mortality risk. In the absence of any new drugs, renal replacement therapy (RRT) is the most important treatment option. Randomized ...controlled trials have concluded that in critically ill patients without an emergency indication for RRT, a watchful waiting strategy is safe; however, further delays in RRT did not seem to confer any benefit, rather was associated with potential harm. During this process, balancing the risks of complications due to an unnecessary intervention with the risk of not correcting a potentially life-threatening complication remains a challenge. Dynamic renal function assessment, especially dynamic assessment of renal demand-capacity matching, combined with renal biomarkers such as neutrophil gelatinase-associated lipocalin and furosemide stress test, is helpful to identify which patients and when the patients may benefit from RRT.
Information about sepsis in mainland China remains scarce and incomplete. The purpose of this study was to describe the epidemiology and outcome of severe sepsis and septic shock in mixed ICU in ...mainland China, as well as the independent predictors of mortality.
We performed a 2-month prospective, observational cohort study in 22 closed multi-disciplinary intensive care units (ICUs). All admissions into those ICUs during the study period were screened and patients with severe sepsis or septic shock were included.
A total of 484 patients, 37.3 per 100 ICU admissions were diagnosed with severe sepsis (n = 365) or septic shock (n = 119) according to clinical criteria and included into this study. The most frequent sites of infection were the lung and abdomen. The overall ICU and hospital mortality rates were 28.7% (n = 139) and 33.5% (n = 162), respectively. In multivariate analyses, APACHE II score (odds ratioOR, 1.068; 95% confidential intervalCI, 1.027-1.109), presence of ARDS (OR, 2.676; 95%CI, 1.691-4.235), bloodstream infection (OR, 2.520; 95%CI, 1.142-5.564) and comorbidity of cancer (OR, 2.246; 95%CI, 1.141-4.420) were significantly associated with mortality.
Our results indicated that severe sepsis and septic shock were common complications in ICU patients and with high mortality in China, and can be of help to know more about severe sepsis and septic shock in China and to improve characterization and risk stratification in these patients.
This study aimed to investigate the effect and mechanism of Pentraxin 3 (PTX3) on myocardial injury in sepsis.
Thirty male C57BL/6 mice were randomly assigned to Groups A, B, or C. Mice in Groups A ...and B were injected with unloaded lentivirus, while mice in Group C were injected with lentivirus encoding PTX3 overexpression. Seven days after injection, septic myocardial injury mouse models were constructed following intraperitoneal injection with LPS in Groups B and C, and mice in Group A were intraperitoneally injected with normal saline. Cardiac function was examined using echocardiography; pathological variation of myocardial cells was measured through HE staining, transmission electron microscopy, and TUNEL staining; and Western blot was used to measure the expression of PI3K/AKT/mTOR pathway-related, autophagy-related, and apoptosis-related proteins in mice myocardial cells.
PTX3 significantly improved cardiac function and structure in sepsis-stricken mice, and PTX3 alleviated cardiac damage caused by sepsis. PTX3 reduced the relative protein expression of p-PI3K, p-AKT, mTOR, LC3I/II, Beclin, ATG5, Bax, Caspase-3, and Caspase-9 in septic mouse cardiomyocytes and increased the relative protein expression of Bcl-2.
PTX3 can attenuate myocardial injury in sepsis due to the down-regulation of apoptosis and autophagy induced by the PI3K/AKT/mTOR pathway.
Endophytic fungi are not only ubiquitous in plants, but also play an important role in the balancing of plant microecosystems. Numerous studies have shown that plant species and environment have a ...significant influence on the richness of endophytic fungi, and endophytic fungi often provide different forms of fitness benefits to their associated host plants. The present work aimed to isolate and identify endophytic fungi harboured in the tissues of the native medicinal plant
Cornus officinalis
and screen beneficial fungi to inhibit cornel pathogens. A total of 208 strains were recovered from 720 tissue segments. The overall colonisation and isolation rates of endophytic fungi were 33.89% and 28.89%, with triennial twigs (53.33%, 55%) and fruits (6.67%, 3.33%) having the highest and lowest rates, respectively. On the basis of morphological characteristics and internal transcribed spacer sequence analysis, 183 isolates were classified into 13 genera. Amongst them,
Alternaria
,
Botryosphaeria
and
Talaromyces
were dominant communities, and their relative abundances were 31.25%, 26.92% and 10.10%, respectively. A detailed calculation of the Shannon diversity (H′ = 1.65) and Margalef’s richness indices (Dmg = 2.30) revealed that the overall biodiversity of fungal endophytes in
C. officinalis
was relatively high, with the stems harbouring the highest diversity. The antagonism assay of 75 representative endophytes on the four main fungal pathogens of
C. officinalis
indicated that nine strains with antibiosis and eight strains with inhibition rate of more than 50% were obtained by the dual culture. To the best of our knowledge, this is the first study that investigated the distribution and antifungal activity of endophytic fungi from the medicinal plant
C. officinalis
.
Patient-ventilator asynchrony is common during mechanical ventilation (MV) in intensive care unit (ICU), leading to worse MV care outcome. Identification of asynchrony is critical for optimizing MV ...settings to reduce or eliminate asynchrony, whilst current clinical visual inspection of all typical types of asynchronous breaths is difficult and inefficient. Patient asynchronies create a unique pattern of distortions in hysteresis respiratory behaviours presented in pressure-volume (PV) loop. Identification method based on hysteretic lung mechanics and hysteresis loop analysis is proposed to delineate the resulted changes of lung mechanics in PV loop during asynchronous breathing, offering detection of both its incidence and 7 major types. Performance is tested against clinical patient data with comparison to visual inspection conducted by clinical doctors. The identification sensitivity and specificity of 11 patients with 500 breaths for each patient are above 89.5% and 96.8% for all 7 types, respectively. The average sensitivity and specificity across all cases are 94.6% and 99.3%, indicating a very good accuracy. The comparison of statistical analysis between identification and human inspection yields the essential same clinical judgement on patient asynchrony status for each patient, potentially leading to the same clinical decision for setting adjustment. The overall results validate the accuracy and robustness of the identification method for a bedside monitoring, as well as its ability to provide a quantified metric for clinical decision of ventilator setting. Hence, the method shows its potential to assist a more consistent and objective assessment of asynchrony without undermining the efficacy of the current clinical practice.
In the ICU ward, septic cirrhotic patients are susceptible to suffering from sepsis-associated encephalopathy and/or hepatic encephalopathy, which are two common neurological complications in such ...patients. However, the mutual pathogenesis between sepsis-associated and hepatic encephalopathies remains unclear. We aimed to identify the mutual hub genes, explore effective diagnostic biomarkers and therapeutic targets for the two common encephalopathies and provide novel, promising insights into the clinical management of such septic cirrhotic patients.
The precious human post-mortem cerebral tissues were deprived of the GSE135838, GSE57193, and GSE41919 datasets, downloaded from the Gene Expression Omnibus database. Furthermore, we identified differentially expressed genes and screened hub genes with weighted gene co-expression network analysis. The hub genes were then subjected to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway functional enrichment analyses, and protein-protein interaction networks were constructed. Receiver operating characteristic curves and correlation analyses were set up for the hub genes. Finally, we explored principal and common signaling pathways by using Gene Set Enrichment Analysis and the association between the hub genes and immune cell subtype distribution by using CIBERSORT algorithm.
We identified seven hub genes-GPR4, SOCS3, BAG3, ZFP36, CDKN1A, ADAMTS9, and GADD45B-by using differentially expressed gene analysis and weighted gene co-expression network analysis method. The AUCs of these genes were all greater than 0.7 in the receiver operating characteristic curves analysis. The Gene Set Enrichment Analysis results demonstrated that mutual signaling pathways were mainly enriched in hypoxia and inflammatory response. CIBERSORT indicated that these seven hub genes were closely related to innate and adaptive immune cells.
We identified seven hub genes with promising diagnostic value and therapeutic targets in septic cirrhotic patients with sepsis-associated encephalopathy and/or hepatic encephalopathy. Hypoxia, inflammatory, and immunoreaction responses may share the common downstream pathways of the two common encephalopathies, for which earlier recognition and timely intervention are crucial for management of such septic cirrhotic patients in ICU.
Light traps are used to determine the temporal and spatial dynamics of the migratory brown planthoppers (BPHs) Nilaparvata lugens. But very little is known whether newly emerged adults respond to ...local light traps during the emigration period. Thus, it is important to evaluate the efficiency of light traps in attracting emigrant and immigrant populations to improve forecasting and control of this pest. The migration periods of N. lugens were determined by field surveys in Fuyang, Zhejiang province in 2012 and Yongfu, Guangxi Zhuang Autonomous Region in 2013. Mark-release-recapture experiments with both newly emerged (unflown) and flight experienced (flown) N. lugens were conducted at the two study sites. The marking method did not have any significant effect on the survival or flight capability of the N. lugens. A total of 4800 marked flown and 8400 unflown BPHs were released at a distance of 10, 20 and 30 m from 45-watt fluorescent actinic light traps. The results showed that without wind (< 3.2 m/s) or rainfall conditions, the overall recapture rate of flown BPHs was higher than that of unflown BPHs (9.60% and 0.92%, respectively; χ21 = 589.66, P < 0.0001). Curve estimation regression analysis showed that flown BPHs were attracted to the light source at a distance of 19.77 m, and unflown BPH at a distance of 5.35 m, with these distances corresponding to a 5% recapture rate. Given that the population dynamics of BPHs in the light traps were not synchronous with that in the fields, our results indicate that only a few emerging BPHs in an infested site can be captured locally by light traps. Therefore, care must be taken in estimating the abundance of the sample to absolute local abundance during sedentary and emigration period.
Wheat sheath blight mainly infected by Rhizoctonia cerealis is one of the soil-borne fungal diseases of wheat worldwide and prevalent in major wheat growing areas in China at present. This study ...aimed to evaluate the antifungal activity of 163 endophytic fungi on R. cerealis. Antifungal strains were identified and their biosynthetic potential was analysed. The antifungal activity of the strains was evaluated via dual-culture antagonism assay. The antifungal strains were identified on the basis of morphological characteristics and internal transcribed spacer gene sequencing. The polyketide synthases (PKSs) and nonribosomal peptide synthetase (NRPS) genes in antifungal strains were detected via specific amplification of chromosomal DNA. Twelve out of 163 fungal strains, including seven strains with matrix competition and five strains with antibiosis, were obtained. The twelve antifungal strains belonged to four genera: Alternaria, Ascochyta, Botryosphaeria, and Talaromyces. The inhibition rate of the seven strains with matrix competition was greater than 50%, with that of Botryosphaeria dothidea S2-33 being the highest at 84.6%. The inhibition zone of Talaromyces assiutensis R-03 amongst the five strains with antibiosis was the widest at up to 7 mm. Among the twelve antifungal strains, the strain S2-16 contained all the genes tested, five B. dothidea strains contained PKS-II and NRPS genes, two Alternaria alternata strains only contained PKS-II gene and the remaining four strains did not contain any.
Acute kidney injury (AKI) is a major complication of cardiac surgery, with high rates of morbidity and mortality. The aim of this study was to identify risk factors for the incidence and prognosis of ...AKI in high-risk patients before and after surgery for acute type A aortic dissection (TAAD) in the intensive care unit (ICU).
We performed a retrospective cohort study from April 2018 to April 2019. The primary end points of this study were morbidity due to AKI and risk factors for incidence, and the secondary end points were mortality at 28 days and risk factors for death.
We enrolled 60 patients, 52 (86.67%) patients developed postoperative AKI, 28 (53.84%) patients died. Preoperative lactic acid level (P=0.022) and cardiopulmonary bypass (CPB) duration (P=0.009) were identified as independent risk factors for postoperative AKI. The 28-day mortality for postoperative patients with TAAD was 46.67%, 53.84% for those with TAAD and AKI, 67.5% for those who required continue renal replacement therapy (CRRT). The risk factors for 28-day mortality due to postoperative AKI for patients requiring CRRT were CPB duration (P=0.019) and norepinephrine dose upon diagnosis of AKI (P=0.037).
Morbidity due to AKI in postoperative patients with TAAD was 86.67%, and preoperative lactic acid level and CPB duration were independent risk factors. The 28-day mortality of postoperative patients with TAAD was 46.67%, 53.84% for those with TAAD and AKI, and 67.5% for those requiring CRRT. CPB duration and norepinephrine dose upon diagnosis of AKI may influence patients' short-term prognosis.
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