A role for small RNAs in DNA double-strand break repair.

Eukaryotes have evolved complex mechanisms to repair DNA double-strand breaks (DSBs) through coordinated actions of protein sensors, transducers, and effectors. Here we show that ∼21-nucleotide small RNAs are produced from the sequences in the vicinity of DSB sites in Arabidopsis and in human cells. We refer to these as diRNAs for DSB-induced small RNAs. In Arabidopsis, the biogenesis of diRNAs requires the PI3 kinase ATR, RNA polymerase IV (Pol IV), and Dicer-like proteins. Mutations in these proteins as well as in Pol V cause significant reduction in DSB repair efficiency. In Arabidopsis, diRNAs are recruited by Argonaute 2 (AGO2) to mediate DSB repair. Knock down of Dicer or Ago2 in human cells reduces DSB repair. Our findings reveal a conserved function for small RNAs in the DSB repair pathway. We propose that diRNAs may function as guide molecules directing chromatin modifications or the recruitment of protein complexes to DSB sites to facilitate repair.

Improving the Surface Oxygen Vacancy Concentration of Bi2O4 through the Pretreatment of the NaBiO3·2H2O Precursor as a High-Performance Visible Light Photocatalyst.

The oxygen-deficient bismuth oxide, Bi2O4, synthesized by a typical hydrothermal method using commercial NaBiO3·2H2O as a raw material only has a relatively low concentration of surface oxygen vacancies (OVs). How to improve the visible light photocatalytic performance of Bi2O4 via tuning its surface OV concentration is still a huge challenge. In this study, improving the surface OVs of Bi2O4 was successfully realized through the pretreatment of commercial NaBiO3·2H2O, including thermal treatment in air and hydrothermal treatment in 10 M NaOH solution, forming NaBiO3·xH2O intermediate products first, and then hydrothermal preparation of Bi2O4 target products using NaBiO3·xH2O instead of commercial NaBiO3·2H2O as the precursor. The enhanced surface OV content not only narrows the band gap of Bi2O4 and thus extends its optical response range but also captures more photoexcited electrons and thus increases the charge carriers' separation efficiency and prolongs the charge carriers' lifetime of Bi2O4. Among the above-mentioned two pretreatment methods, the effects of the hydrothermal pretreatment are superior to those of the thermal treatment, involving the increase of surface OVs, the optical harvesting capacity, and the charge carriers' separation efficiency. Accordingly, Bi2O4 prepared by the hydrothermal pretreatment route exhibits the optimal visible light catalytic performance toward the removal of methyl orange (MO) and phenol due to its most abundant surface OV concentration, which is 2.59 times and 4.26 times higher than that of Bi2O4 synthesized directly by the commercial NaBiO3·2H2O route, respectively. Holes (h+) and superoxide radicals (•O2-) are identified as the main active species, while singlet oxygen (1O2) and hydroxyl radicals (•OH) are verified as the second and third important active species for organic pollutant removal, respectively. This work has developed a novel strategy to promote the catalytic performance of single Bi2O4 induced by the enhanced surface OV concentration through the pretreatment of the precursor, commercial NaBiO3·2H2O.

Left Atrial Enlargement is Associated with Stroke Severity with Cardioembolic and Cryptogenic Subtypes in a Chinese Population.

BACKGROUND: Left atrial enlargement is associated with increased risk for stroke. However, few studies that evaluated the correlation between left atrial size and ischemic stroke severity. In this study, we aim to evaluate the association between left atrial size and stroke severity, especially with cardioembolic and cryptogenic stroke in the Chinese population. METHODS: A total of 1271 patients with acute ischemic stroke were included in this study. Echocardiographic left atrial diameter was measured and indexed to height. Stroke severity was assessed at admission with the National Institutes of Health Stroke Scale (NIHSS). Moderate-to-severe neurologic deficit was defined as NIHSS greater than or equal to 5. Patients were divided into mild, moderate, or severe abnormal left atrial size by tertile distribution. Binary logistic regression analysis was used to identify independent predictors of severe stroke after adjustment. RESULTS: Among all enrolled patients, 328 (25.8%) were classified into moderate-to severe stroke severity (NIHSS ≥ 5). In the multivariable model, compared with the lowest tertile of left atrial size, the odds ratio for moderate-to-severe neurologic deficit was 0.902 (95% CI, 0.644-1.264, P = .550) when left atrial size was the highest tertile. Of all patients, 190 patients were further categorized as cardioembolic and cryptogenic subtypes, and 70 (36.8%) were classified into moderate-to-severe stroke severity. After adjusting for confounders, compared with the lowest tertile, the top tertile of left atrial size was significantly associated with moderate-to-severe stroke (3.156, 95% CI, 1.143-8.711, P = .027). CONCLUSION: Left atrial enlargement was associated with more severe initial neurologic deficits of embolic subtypes (cardioembolic and cryptogenic stroke) in patients with acute ischemic stroke.

HuoXueTongFu Formula Alleviates Intraperitoneal Adhesion by Regulating Macrophage Polarization and the SOCS/JAK2/STAT/PPAR-γ Signalling Pathway.

Intraperitoneal adhesion is a common complication after abdominal surgery, which seriously affects the quality of life of patients. HuoXueTongFu Formula (HXTF) plays an important role in the prevention and treatment of intraperitoneal adhesions. However, the molecular-related mechanisms are still not fully known. In this study, the model of Intrapetitoneal adhesion was established by cecum abrasion and treated with HXTF for one week. RAW264.7 cells were given LPS, IFN-γ, IL-4, HXTF-medicated serum, and PPAR-γ agonist/antagonist, respectively. Histopathology, flow cytometry, ELISA, real-time PCR, and Western blotting were used to further detect the related protein, M1/M2 polarization tendency, and PPAR-γ nuclear translocation. The deposition of collagen fibres reduced in the local area of rats after the operation with HXTF treatment. Similar to IL-4, HXTF induced a tendency for macrophages to polarize toward M2 and promoted peroxisome proliferator-activated receptor-gamma (PPAR-γ) nuclear translocation. Furthermore, the use of HXTF and PPAR-γ agonists downregulated macrophage M1 polarization-related factors IL-1, IL-6, and TNF-alpha and upregulated M2 polarization-related factors IL-4, IL-10, and TGF-beta 1. Meanwhile, the use of HXTF and PPAR-γ agonists downregulated the SOCS3/JAK2/STAT1 pathway and activated the SOCS1/STAT6/PPAR-γ pathway. These results show that HXTF may reduce intraperitoneal adhesion by inducing macrophage M2 polarization and regulating the SOCS/JAK2/STAT/PPAR-γ pathway.

The RNA surveillance complex Pelo-Hbs1 is required for transposon silencing in the Drosophila germline.

Silencing of transposable elements (TEs) in the metazoan germline is critical for genome integrity and is primarily dependent on Piwi proteins and associated RNAs, which exert their function through both transcriptional and posttranscriptional mechanisms. Here, we report that the evolutionarily conserved Pelo (Dom34)-Hbs1 mRNA surveillance complex is required for transposon silencing in the Drosophila germline. In pelo mutant gonads, mRNAs and proteins of some selective TEs are up-regulated. Pelo is not required for piRNA biogenesis, and our studies suggest that Pelo may function at the translational level to silence TEs: This function requires interaction with Hbs1, and overexpression of RpS30a partially reverts TE-silencing defects in pelo mutants. Interestingly, TE silencing and spermatogenesis defects in pelo mutants can also effectively be rescued by expressing the mammalian ortholog of Pelo. We propose that the Pelo-Hbs1 surveillance complex provides another level of defense against the expression of TEs in the germline of Drosophila and possibly all metazoa.

H3.3-H4 tetramer splitting events feature cell-type specific enhancers.

Previously, we reported that little canonical (H3.1-H4)(2) tetramers split to form "hybrid" tetramers consisted of old and new H3.1-H(4) dimers, but approximately 10% of (H3.3-H4)2 tetramers split during each cell cycle. In this report, we mapped the H3.3 nucleosome occupancy, the H3.3 nucleosome turnover rate and H3.3 nucleosome splitting events at the genome-wide level. Interestingly, H3.3 nucleosome turnover rate at the transcription starting sites (TSS) of genes with different expression levels display a bimodal distribution rather than a linear correlation towards the transcriptional activity, suggesting genes are either active with high H3.3 nucleosome turnover or inactive with low H3.3 nucleosome turnover. H3.3 nucleosome splitting events are enriched at active genes, which are in fact better markers for active transcription than H3.3 nucleosome occupancy itself. Although both H3.3 nucleosome turnover and splitting events are enriched at active genes, these events only display a moderate positive correlation, suggesting H3.3 nucleosome splitting events are not the mere consequence of H3.3 nucleosome turnover. Surprisingly, H3.3 nucleosomes with high splitting index are remarkably enriched at enhancers in a cell-type specific manner. We propose that the H3.3 nucleosomes at enhancers may be split by an active mechanism to regulate cell-type specific transcription.

Establishment of a Risk Prediction Model for Metabolic Syndrome in High Altitude Areas in Qinghai Province, China: A Cross-Sectional Study.

Purpose: The prevalence of metabolic syndrome (MetS) is increasing worldwide, and early prediction of MetS risk is highly beneficial for health outcomes. This study aimed to develop and validate a nomogram to predict MetS risk in Qinghai Province, China, and it provides a methodological reference for MetS prevention and control in Qinghai Province, China. Patients and Methods: A total of 3073 participants living between 1900 and 3710 meters above sea level in Qinghai Province participated in this study between March 2014 and March 2016. We omitted 12 subjects who were missing diagnostic component data for MetS, ultimately resulting in 3061 research subjects, 70% of the subjects were assigned randomly to the training set, and the remaining subjects were assigned to the validation set. The least absolute shrinkage and selection operator (LASSO) regression analysis method was used for variable selection via running cyclic coordinate descent with 10-fold cross-validation. Multivariable logistic regression was then performed to develop a predictive model and nomogram. The receiver operating characteristic (ROC) curves was used for model evaluation, and calibration plot and decision curve analysis (DCA) were used for model validation. Results: Of 24 variables studied, 6 risk predictors were identified by LASSO regression analysis: hyperlipidaemia, hyperglycemia, abdominal obesity, systolic blood pressure (SBP), diastolic blood pressure (DBP), and body mass index (BMI). A prediction model including these 6 risk factors was constructed and displayed good predictability with an area under the ROC curve of 0.914 for the training set and 0.930 for the validation set. DCA revealed that if the threshold probability of MetS is less than 82%, the application of this nomogram is more beneficial than both the treat-all or treat-none strategies. Conclusion: The nomogram developed in our study demonstrated strong discriminative power and clinical applicability, making it a valuable reference for meets prevention and control in the plateau areas of Qinghai Province.

Analysis of Nursing Effect of Comprehensive Nursing Intervention on Hemodialysis Patients with Uremia.

Uremic pruritus affects 50-90% of hemodialysis patients, making it one of the most frequent medical issues among this group. Pruritus can lead to skin infections, desquamation, pathological skin changes, sleep problems, anxiety, depression, and social problems. The epidemic of uremia pneumonia has put a lot of stress on hemodialysis patients, resulting in negative feelings. As a result, during the prevention and control of uremia, rigorous management and improved nursing intervention are critical. During the uremia disease outbreak, this study will examine and assess the impact of clinically refined nurse intervention on patients receiving maintenance hemodialysis.

Prolonged Maternal Separation Induces the Depression-Like Behavior Susceptibility to Chronic Unpredictable Mild Stress Exposure in Mice.

Early life stress is an important determinant for developing depression later in life. It is reported that maternal separation (MS) could trigger stress sensitivity in adulthood when exposed to stress again. However, it could also result in resilience to stress-induced depression. The conclusions are contradictory. To address this issue, C57BL/6N newborn pups were exposed to either daily short MS (MS for 15 min per day; MS15) or prolonged MS (MS for 180 min per day; MS180) from the first day postpartum (PD1) to PD21. Adult mice were then subjected to chronic unpredictable mild stress (CUMS) exposure from PD64 to PD105. The behavior tests such as the forced swimming test (FST), tail suspension test (TST), and open-field test were performed once a week during this time. Besides, the hippocampal neurosteroids, serum stress hormones, and hippocampal monoamine neurotransmitters were measured at PD106. We found that mice in the MS180 group displayed the reduced struggling time and the increased latency to immobility in both FST and TST. However, there was no significant difference in the MS15 group. The levels of hippocampal neurosteroids (progesterone and allopregnanolone) were decreased, and the serum levels of corticosterone, corticotropin-releasing hormone, and adrenocorticotropic hormone were overexpressed in the MS180 group. Besides, the expressions of monoamine neurotransmitters such as 5-hydroxytryptamine and 5-hydroxy indole acetic acid significantly decreased in the MS180 group, but not in the MS15 group. All findings revealed that prolonged MS, rather than short MS, could increase the susceptibility to depression-like behavior when reexposed to stress in adulthood. However, future studies are warranted to identify the underlying neuromolecular mechanism of the MS experience on the susceptibility to adult stress reexposure.

[Impact of Land Use Type on the Stability and Organic Carbon Content of Soil Aggregates in the Weibei Dryland].

Soil aggregates are important indicators of soil quality and sustainable land utilization, and impact the retention abilities of water and fertilizers and the release of nutrients in soil. This study aimed to understand the effects of two land use types (an orchard and farmland) on the distribution, stability, and organic carbon content of soil aggregates, and provides a theoretical basis for the optimal management of the soil carbon pool in the Weibei Dryland of the Loess Plateau. We examined the soils from an orchard and from farmland by simultaneous sampling and wet sieving; the proportions of large macroaggregates (>2 mm), small macroaggregates (0.25-2 mm), microaggregates (0.053-0.25 mm), and silt and clay (<0.053 mm) were then determined; the content of organic carbon in each aggregate fraction at soil depths of 0-40 cm were also measured, and the total organic carbon content of all aggregates fractions was determined for each soil. The results showed that the type of agricultural land use had a significant effect on the distribution and stability of soil aggregates in the 0-20 cm soil layer, with the relative proportions of the different sized aggregates (>2, 0.25-2, 0.053-0.25, and<0.053 mm) being 12.9%, 51.3%, 28.8%, and 7.0% in the orchards, respectively, and 8.3%, 49.7%, 33.6%, and 8.4% on the farmland, respectively. The proportion of macro-aggregates (>0.25 mm) was significantly higher in the orchard soils than in the farmland soils. Mean weight diameter (MWD) and geometric mean diameter (GMD) are important indicators of the soil aggregate stability; the MWD and GWD of the farmland soils were significantly lower than the orchard soils in the 0-40 cm depth zone (P<0.05). The effects of different land use types on the organic carbon content of soil aggregates was most marked in the 0-10 cm layer. Compared with farmland, the organic carbon content in the large aggregates, intermediate aggregates, micro-aggregates, and the silt and clay fraction of orchard soils were relatively increased by 56.0% (P<0.05), 57.1% (P<0.05), 40.8% (P>0.05), and 13.0% (P>0.05), respectively. Organic carbon storage in each aggregate class (excluding the<0.053 mm fraction) in the orchard soils was higher than in the farmland soils. In the orchard soils, the proportion of soil macro-aggregates (>0.25 mm) and the associated organic carbon content was elevated, damage to aggregates was reduced, and the organic carbon stability was enhanced. In general, the soil aggregate stability and organic carbon content of orchard soils were higher than for the farmland soils. Orchards appear to enhance the physical stability of aggregates with respect to soil organic carbon, contribute to soil organic carbon accumulation, and thus promote soil carbon sequestration.

microRNA expression in hepatitis B virus infected primary treeshrew hepatocytes and the independence of intracellular miR-122 level for de novo HBV infection in culture.

Infection of Hepatitis B virus (HBV) in hepatocytes has been known to be controlled by multiple cellular factors, while the relationship of the infection and liver microRNAs remains obscure. In this study, a miRNA database, containing 168 unique mature miRNA members from primary hepatocytes of a primate-like animal, northern treeshrew (Tupaia belangeri) that is the only species susceptible for HBV infection other than human and chimpanzee, was established. The relative level of a liver predominant microRNA, miR-122, was markedly increased upon HBV infection of the primary tupaia hepatocyte (PTH). However, introducing neither miR-122 nor its antagonist anti-miR-122 into PTHs, or, HepG2-NTCP that is HepG2 cells with the newly identified receptor sodium taurocholate cotransporting polypeptide (NTCP) did not alter the viral infection on these cells. These data suggest that de novo HBV infection of cultured hepatocytes does not depend on the expression level of intracellular miR-122 of the target cells.