Binding by the Polycomb complex component BMI1 and H2A monoubiquitination shape local and long-range interactions in the Arabidopsis genome.

Three-dimensional (3D) chromatin organization is highly dynamic during development and seems to play a crucial role in regulating gene expression. Self-interacting domains, commonly called topologically associating domains (TADs) or compartment domains (CDs), have been proposed as the basic structural units of chromatin organization. Surprisingly, although these units have been found in several plant species, they escaped detection in Arabidopsis (Arabidopsis thaliana). Here, we show that the Arabidopsis genome is partitioned into contiguous CDs with different epigenetic features, which are required to maintain appropriate intra-CD and long-range interactions. Consistent with this notion, the histone-modifying Polycomb group machinery is involved in 3D chromatin organization. Yet, while it is clear that Polycomb repressive complex 2 (PRC2)-mediated trimethylation of histone H3 on lysine 27 (H3K27me3) helps establish local and long-range chromatin interactions in plants, the implications of PRC1-mediated histone H2A monoubiquitination on lysine 121 (H2AK121ub) are unclear. We found that PRC1, together with PRC2, maintains intra-CD interactions, but it also hinders the formation of H3K4me3-enriched local chromatin loops when acting independently of PRC2. Moreover, the loss of PRC1 or PRC2 activity differentially affects long-range chromatin interactions, and these 3D changes differentially affect gene expression. Our results suggest that H2AK121ub helps prevent the formation of transposable element/H3K27me1-rich long loops and serves as a docking point for H3K27me3 incorporation.

Chromatin remodeling complexes regulate genome architecture in Arabidopsis.

In eukaryotes, three-dimensional (3D) chromatin architecture maintains genome stability and is important in regulating gene transcription. However, little is known about the mechanisms by which diverse ATP-dependent chromatin remodeling complexes regulate the 3D chromatin structure in plants. We examined the 3D chromatin structure within the ATPase subunit of the SWI/SNF, ISWI, INO80, and CHD remodeling complexes in wild-type (WT) and mutant Arabidopsis thaliana plants by combining high-throughput sequencing with in situ Hi-C, the enrichment of histone marks, nucleosome density, and gene expression. We found that compartment regions switched and compartmental strength was significantly weakened in all four enzyme mutants. Chromatin remodeling complexes differentially regulated the nucleosome distribution pattern and density within the switching compartments. Alterations of nucleosome distribution pattern and density were associated with a reduction in H3K27me3 levels in the chromatin remodeling enzyme mutants and led to compartment switching. Our data show that chromatin remodeling complexes regulate the linear nucleosome distribution pattern and density to promote H3K27me3 deposition, which in turn regulates 3D chromatin structure.

Integrated analysis of transcriptome and small RNAome reveals regulatory network of rapid and long-term response to heat stress in Rhododendron moulmainense.

MAIN CONCLUSION: The post-transcriptional gene regulatory pathway and small RNA pathway play important roles in regulating the rapid and long-term response of Rhododendron moulmainense to high-temperature stress. The Rhododendron plays an important role in maintaining ecological balance. However, it is difficult to domesticate for use in urban ecosystems due to their strict optimum growth temperature condition, and its evolution and adaptation are little known. Here, we combined transcriptome and small RNAome to reveal the rapid response and long-term adaptability regulation strategies in Rhododendron moulmainense under high-temperature stress. The post-transcriptional gene regulatory pathway plays important roles in stress response, in which the protein folding pathway is rapidly induced at 4 h after heat stress, and alternative splicing plays an important role in regulating gene expression at 7 days after heat stress. The chloroplasts oxidative damage is the main factor inhibiting photosynthesis efficiency. Through WGCNA analysis, we identified gene association patterns and potential key regulatory genes responsible for maintaining the ROS steady-state under heat stress. Finally, we found that the sRNA synthesis pathway is induced under heat stress. Combined with small RNAome, we found that more miRNAs are significantly changed under long-term heat stress. Furthermore, MYBs might play a central role in target gene interaction network of differentially expressed miRNAs in R. moulmainense under heat stress. MYBs are closely related to ABA, consistently, ABA synthesis and signaling pathways are significantly inhibited, and the change in stomatal aperture is not obvious under heat stress. Taken together, we gained valuable insights into the transplantation and long-term conservation domestication of Rhododendron, and provide genetic resources for genetic modification and molecular breeding to improve heat resistance in Rhododendron.

Correlates of Sleep Disturbance Experienced by Informal Caregivers of Persons Living with Dementia: A Systematic Review.

OBJECTIVES: This study aims to comprehensively review and update the literature concerning the correlates of sleep disturbance among caregivers of persons living with Alzheimer's disease and related dementias to identify gaps in the literature and antecedent targets for interventions. METHODS: We searched PubMed, CINAHL, PsycINFO, and Embase using terms related to "sleep," "caregiver," and "dementia." RESULTS: Thirty-six articles were included in this review. Based on the antecedents within the 3P model of insomnia, predisposing factors associated with caregiver sleep included caregiver demographics, and physiological factors like genotype and biomarkers. Precipitating factors related to caregiver sleep included caregiving status and responsibilities, and person living with dementia factors. CONCLUSIONS: Sleep disturbance is a significant issue for caregivers of persons living with dementia. However, this review has identified multiple precipitating factors that are modifiable targets for interventions to improve or enhance caregiver sleep. CLINICAL IMPLICATIONS: Numerous predisposing and precipitating factors contribute to caregivers of persons living with dementia being susceptible to sleep disturbance. Healthcare providers should ask patients about their caregiving status during annual visits. Healthcare providers should also evaluate caregivers' sleep patterns, and the predisposing and precipitating factors of sleep disturbance, with a focus on the modifiable factors, to enable timely intervention.

Recombinant porcine epidermal growth factor-secreting Lactococcus lactis promotes the growth performance of early-weaned piglets.

BACKGROUND: Epidermal growth factor (EGF) is an important growth factor in regulation of cell proliferation, differentiation, survival and apoptosis. Studies showed that food-grade Lactococcus lactis (L. lactis) and NICE expression system have superior performance in exogenous protein expression. This study aimed to construct and express porcine EGF (pEGF), and use L. lactis as vehicle for producing and delivering pEGF. Furthermore, investigating biological activity of pEGF and exploring applications feasibility of combination effects of L. lactis and pEGF on early weaned piglets' production. RESULTS: A recombinant Lactococcus lactis which produced and secreted pEGF at 1000 ng/ml in culture supernatant was generated. Secreted pEGF was a fully biologically active protein, as demonstrated by its capacity to stimulate L929 mouse fibroblast cell line proliferation in vitro. For in vivo study, forty piglets were randomly allocated to control, antibiotic control, empty vector-expressing L. lactis (LL-EV) and pEGF-secreting L. lactis (LL-pEGF). After 14 d of rearing, final body weight and average daily gain in LL-pEGF were greater (P < 0.05, 8.95 vs. 8.37 kg, 206.1 vs. 157.7 g/day, respectively) than those in control, but no significant differences between LL-pEGF, LL-EV and antibiotic control. Overall period average daily feed intake was higher in LL-pEGF, LL-EV and antibiotic control than in control (P < 0.05, 252.9, 255.6, 250.0, 207.3 g/day, respectively). No significant difference was observed on ADFI/ADG. LL-pEGF increased villous height in the duodenum, jejunum and ileum than in control and LL-EV (P < 0.05). Sucrase in the 3 intestinal segments, aminopeptidase A in the duodenum and Jejunum, aminopeptidase N and dipeptidase IV in the duodenum in LL-pEGF were higher than those in control (P < 0.05). Furthermore, Escherichia coli and Enterococcus counts decreased in the ileum and Lactobacillus increased in the ileum and cecum digesta in LL-pEGF compare with the control (P < 0.05). Lactobacillus increased in the cecum in LL-EV compared with control and antibiotic control (P < 0.05). CONCLUSION: We have generated a recombinant Lactococcus lactis which produced and secreted fully biologically active porcine EGF. Oral administration of pEGF-secreting L. lactis had beneficial effects on intestinal health and performance of early-weaned piglets.

Imaging of Sarcopenia in Type 2 Diabetes Mellitus.

Sarcopenia is an age-related condition characterized by the loss of skeletal muscle mass, muscular strength, and muscle function. In older adults, type 2 diabetes mellitus (T2DM) constitutes a significant health burden. Skeletal muscle damage and deterioration have emerged as novel chronic complications in patients with diabetes, often linked to their increased longevity. Diabetic sarcopenia has been associated with increased rates of hospitalization, cardiovascular events, and mortality. Nevertheless, effectively managing metabolic disorders in patients with T2DM through appropriate therapeutic interventions could potentially mitigate the risk of sarcopenia. Utilizing imaging technologies holds substantial clinical significance in the early detection of skeletal muscle mass alterations associated with sarcopenia. Such detection is pivotal for arresting disease progression and preserving patients' quality of life. These imaging modalities offer reproducible and consistent patterns over time, as they all provide varying degrees of quantitative data. This review primarily delves into the application of dual-energy X-ray absorptiometry, computed tomography, magnetic resonance imaging, and ultrasound for both qualitative and quantitative assessments of muscle mass in patients with T2DM. It also juxtaposes the merits and limitations of these four techniques. By understanding the nuances of each method, clinicians can discern how best to apply them in diverse clinical scenarios.

Characteristics of Older Adults with Alzheimer's Disease Who Were Hospitalized during the COVID-19 Pandemic: A Secondary Data Analysis.

We aim to investigate the relationships between the population characteristics of patients with Alzheimer's Disease (AD) and their Healthcare Utilization (HU) during the COVID-19 pandemic. Electronic health records (EHRs) were utilized. The study sample comprised those with ICD-10 codes G30.0, G30.1, G30.8, and G30.9 between 1 January 2020 and 31 December 2021. Pearson's correlation and multiple regression were used. The analysis utilized 1537 patient records with an average age of 82.20 years (SD = 7.71); 62.3% were female. Patients had an average of 1.64 hospitalizations (SD = 1.18) with an average length of stay (ALOS) of 7.45 days (SD = 9.13). Discharge dispositions were primarily home (55.1%) and nursing facilities (32.4%). Among patients with multiple hospitalizations, a negative correlation was observed between age and both ALOS (r = -0.1264, p = 0.0030) and number of hospitalizations (r = -0.1499, p = 0.0004). Predictors of longer ALOS included male gender (p = 0.0227), divorced or widowed (p = 0.0056), and the use of Medicare Advantage and other private insurance (p = 0.0178). Male gender (p = 0.0050) and Black race (p = 0.0069) were associated with a higher hospitalization frequency. We recommend future studies including the co-morbidities of AD patients, larger samples, and longitudinal data.

Factors associated with memory of informal caregivers: A scoping review protocol.

The ability to retain and remember information (memory) is essential to caregiving tasks. There is evidence that caregivers are at greater risk for experiencing deteriorations in cognitive status than non-caregivers, especially memory; however, we have a limited understanding of factors that are related to changes in caregiver memory. This scoping review intends to comprehensively map factors related to caregiver memory reported in the literature within the chronic caregiving context. Specific aims include (1) identifying factors related to caregiver memory; (2) examining how caregiver memory has been measured; and (3) describing changes in caregiver memory during their caregiving period. This review will be conducted following Arksey and O'Malley's framework and reported using the PRISMA guidelines for Scoping Reviews (PRISMA-ScR). Studies will be included if (1) the studies focus on home-based unpaid long term family caregiving; (2) study participants (patients), of any age, have one (or more) chronic illness or disability and receive care from a caregiver for 6 months or more; (3) caregivers are adults (> = 18 years of age). Any chronic disease or condition will be included. The search will encompass gray literature and peer-reviewed literature in MEDLINE (via Ovid), CINAHL Plus with Full Text (via EBSCOhost), Embase (via Elsevier), APA PsycINFO (via EBSCOhost), Sociology Source Ultimate (via EBSCOhost), and ProQuest Dissertations and Theses Global. Data extraction will include specific details about the participants, concept, context, study methods, and key caregiver-related findings. The Caregiver Health Model will provide a framework to categorize factors that impact caregivers' memory including caregiver health promotion activities, caregiver attitudes and beliefs, caregiver task, and caregiver needs. Factors that do not fall into the Caregiver Health Model domains will be organized by emerging themes.

Qinglong Zhidong Decoction Alleviated Tourette Syndrome in Mice via Modulating the Level of Neurotransmitters and the Composition of Gut Microbiota.

Qinglong Zhidong Decoction (QLZDD), a traditional Chinese medicine (TCM) prescription, has been effectively used to alleviate Tourette syndrome (TS) in children. However, the therapeutic mechanism of QLZDD on TS has not been evaluated. The present study aims to elucidate the therapeutic effect and the possible therapeutic mechanism of QLZDD on TS in mouse model. A 3,3-iminodipropionitrile (IDPN, 350 mg/kg)-induced-TS mouse model was established. The mice were randomly divided into the control group, the model group, the haloperidol group (14 mg/kg), the low-, middle-, or high-QLZDD-dose groups (6.83 g/kg, 13.65 g/kg, 27.3 g/kg). QLZDD was administrated orally once a day for 4 weeks. The tic-like behavior was recorded weekly. Then, neurotransmitters and neurotransmitter receptors were analyzed by ELISA, immunohistochemistry (IHC), and quantitative reverse transcription PCR in striatum. Further, the alteration to intestinal flora was monitored by 16s rRNA sequencing, and the role of gut microbiota in the alleviation of TS by QLZDD was investigated. QLZDD ameliorated the tic-like behavior, and decreased the level of excitatory neurotransmitters such as Glu and DA and increased the level of the inhibitory neurotransmitter GABA significantly. Moreover, QLZDD significantly blocked the mRNA expression and the protein expression of D1R and D2R in the striatum, while activated the levels of DAT and GABAR. Interestingly, QLZDD mediated the composition of gut microbiota by increasing the abundance of Lactobacillus and Bacteroides but decreasing the abundance of Alloprevotella and Akkermansia. Taken together, QLZDD ameliorated the tic-like behavior in TS mouse, its mechanism of action may be associated with restoring the balance of gut microbiota and neurotransmitters. The study indicated a promising role of QLZDD in alleviating TS and a therapeutic strategy for fighting TS in clinical settings.

Traditional Chinese Medicine Strategy for Patients with Tourette Syndrome Based on Clinical Efficacy and Safety: A Meta-Analysis of 47 Randomized Controlled Trials.

OBJECTIVE: Although increasing evidence reveals the efficacy of traditional Chinese medicine (TCM) and its safety on Tourette Syndrome (TS) patients, whether TCM is indeed improving TS remains unclear. The purpose of the current study is to perform a meta-analysis to evaluate the efficacy and safety of TCM on treating TS patients. METHOD: An elaborate search strategy was conducted based on several databases including Medline, Embase, Cochrane, Web of Science, CINAHL, CBM, VIP, CNKI, and Wanfang Data in order to identify the relevant randomized controlled trials (RCTs) from their inception to as late as May 1st, 2020. General information and data needing analysis were extracted simultaneously for the necessity of various analyses such as descriptive analysis and metaquantitative analysis. RESULTS: Forty-seven trials with 5437 TS patients in total were eventually included according to our criteria. All trials were conducted in China, and the publication years ranged from 2004 to 2017. In terms of clinical efficacy, clinical symptoms of patients with TCM were more likely to be improved compared with the control group (odds ratio, OR = -1.29, 95% confidence interval, CI: -2.54 to -0.06, I 2 = 0.00%). As to the outcome of recurrence rate, the pooled results revealed that the TCM group was more inclined to stabilize the recurrence (OR = 0.44, 95% CI: 0.24 to 0.78, I 2 = 0.00%). Similar results were observed in adverse reaction (OR = 0.32, 95% CI: 0.24 to 0.43, I 2 = 32.90%). CONCLUSION: The results of our study recommend applying TCM to treat TS patients for better efficacy and safety. Results need to be interpreted cautiously due to certain limitations in our study.

Mortality of Different Stages of Plodia interpunctella (Lepidoptera: Pyralidae) at Three Temperatures in Controlled Atmosphere of High Nitrogen.

The lethal exposure time to controlled atmospheres of high nitrogen at stored grain temperatures is an important information for control of stored-product insects. The mortality of 1-d-old egg, 1-wk-old (first or second instar) larva, 3-wk-old (fourth or fifth instar) larva, and 1-d-old pupa of Plodia interpunctella (Hübner) was determined at 18 ± 1, 23 ± 1, and 28 ± 1°C in 98% N2 mixed with air. At 18°C, the lethal exposure times to achieve 100% mortality were 12.7 ± 0.7, 16.3 ± 0.3, 19.7 ± 0.7, and 14.7 ± 0.7 d for 1-d-old egg, 1-wk-old larva, 3-wk-old larva, and 1-d-old pupa, respectively. Temperature had significant effect on the lethal exposure time, and increase of the temperature significantly decreased the lethal exposure time. The order of the insect stages from the highest to lowest for LT50 values was follows: 3-wk-old larva > 1-wk-old larva > 1-d-old pupa ≥ 1-d-old egg. The minimum lethal exposure times required to kill all stages of P. interpunctella were about 20, 16, and 12 d at 18, 23, and 28°C, respectively.

Reproductive Hormone and Transcriptomic Responses of Pituitary Tissue in Anestrus Gilts Induced by Nutrient Restriction.

The onset of estrus is a critical sign of female sexual maturity. The pituitary plays a vital role in this process by the secretion of reproductive hormones. To investigate the effects of nutrient restriction on reproductive function and the underlying mechanisms involved, deep RNA sequencing of pituitary gland tissue was carried out to determine the differentially expressed genes (DEGs) between gilts in normal estrus, and gilts in which anestrus was induced by nutrient restriction. Gilts which had gone through two estrus cycles were fed a normal (CON, 2.86kg/d, n = 10) or nutrient restricted (NR, 1kg/d, n = 10) diet. The NR gilts experienced another three estrus cycles, but did not express estrus symptoms at the anticipated 6th and 7th cycles. Body weight gain in NR gilts was significantly decreased by nutrient restriction. Gilts were considered as anestrus when blood progesterone concentrations lower than 1.0 ng/mL from three consecutive blood samples were recorded. Circulating concentrations of progesterone (< 1.0 ng/mL vs. 2.1 ng/mL) and estradiol (208.6 ng/mL vs. 371.8 ng/mL) were significantly lower in the NR gilts than in the CON gilts. Between 5,360,000 and 5,370,000 sequence reads per sample from the CON and NR gilts' pituitaries were obtained and mapped to the porcine genome. Analysis of read counts revealed 185 DEGs. Expression of selected genes was validated by the use of quantitative real-time RT-PCR. Bioinformatic analysis identified that the genes identified were enriched in the GO terms "neuroactive ligand-receptor interaction", "GnRH signaling pathway" and "immune response system". Our findings provide a new perspective for understanding the nutrient restriction-induced reproductive impairment at the pituitary transcriptional level, and how this is linked to hormone secretion. Moreover, the transcriptomic changes in anestrus gilts associated with nutrient restriction could be a resource for targeted studies of genes and pathways potentially involved in the regulation of reproductive function and animal health.

Proteomic Analysis of Fetal Ovary Reveals That Ovarian Developmental Potential Is Greater in Meishan Pigs than in Yorkshire Pigs.

Time-dependent expression of functional proteins in fetal ovaries is important to understand the developmental process of the ovary. This study was carried out to enhance our understanding of the developmental process of porcine fetal ovaries and to better address the differences in fetal ovary development of local and foreign pigs. The objective of the present study is to test the expression of key proteins that regulate the growth and development of fetal ovaries in Meishan and Yorkshire porcine breeds by using proteomics technology. Six Meishan and 6 Yorkshire pregnant gilts were used in this experiment. Fetal ovaries were obtained from Yorkshire and Meishan gilts on days 55 and 90 of the gestation period. Using 2D-DIGE (two dimensional-difference in gel electrophoresis) analysis, the results showed that there are about 1551 and 1400 proteins in gilt fetal ovaries on days 55 and 90, respectively of the gestation. Using MALDI TOF-TOF MS analysis, 27 differentially expressed proteins were identified in the fetal ovaries of the 2 breeds on day 55 of gestation, and a total of 18 proteins were identified on day 90 of gestation. These differentially expressed proteins were involved in the regulation of biological processes (cell death, stress response, cytoskeletal proteins) and molecular functions (enzyme regulator activity). We also found that alpha-1-antitrypsin, actin, vimentin, and PP2A proteins promote the formation of primordial follicles in the ovaries of Yorkshire pigs on day 55 of gestation while low expression heat shock proteins and high expression alpha-fetoproteins (AFP) may promote Meishan fetal ovarian follicular development on day 90 of gestation. These findings provide a deeper understanding of how reduced expression of heat shock proteins and increased expression of AFP can significantly reduce the risk of reproductive disease in obese Meishan sows. Our study also shows how these proteins can increase the ovulation rate and may be responsible for the low reproductive efficiency reported in other obese breeds. The ovarian developmental potential was found to be greater in Meishan pigs than in Yorkshire pigs.