Community-based rehabilitation interventions on quality of care for people with schizophrenia in China (CRISC): study protocol for a cluster-randomized controlled trial.

BACKGROUND: International consensus shows that community-based rehabilitation (CBR) service is an effective way to improve functioning and negative symptoms and address the treatment gap for schizophrenia. Rigorous trials are needed in China to demonstrate effective and scalable CBR interventions to significantly improve outcomes for people with schizophrenia and to provide evidence of the economic benefits. The objectives of this trial are to examine the effectiveness of CBR as an adjunct to test the usual facility-cased care (FBC) in comparison to FBC alone in improving a range of outcomes in people with schizophrenia and their caregivers. METHODS: This trial is a cluster randomized controlled trial design in China. The trial will be conducted at three districts of Weifang city, Shandong province. Eligible participants will be identified from the psychiatric management system where community-dwelling patients with schizophrenia have been registered. Participants will be recruited after providing informed consent. 18 sub-districts will be randomly allocated in a 1:1 ratio to facility-based care (FBC) plus CBR (intervention arm) or FBC alone (control arm). The structured CBR intervention will be delivered by trained psychiatric nurses or community health workers. We aim to recruit 264 participants. The primary outcomes include symptoms of schizophrenia, personal and social function, quality of life, family burden of caring, etc. The study will be conducted according to good ethical practice, data analysis and reporting guidelines. DISCUSSION: If the hypothesized clinical benefit and cost-effectiveness of CBR intervention are confirmed, this trial will provide significant implications for policy makers and practitioners to scale up rehabilitation services, as well as for people with schizophrenia and their family to promote recovery and social inclusion, and to alleviate the burden of care. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2200066945). Registered December 22, 2022.

Whole-genome characterization of chronological age-associated changes in methylome and circular RNAs in moso bamboo (Phyllostachys edulis) from vegetative to floral growth.

In mammals, DNA methylation is associated with aging. However, age-related DNA methylation changes during phase transitions largely remain unstudied in plants. Moso bamboo (Phyllostachys edulis) requires a very long time to transition from the vegetative to the floral phase. To comprehensively investigate the association of DNA methylation with aging, we present here single-base-resolution DNA methylation profiles using both high-throughput bisulfite sequencing and single-molecule nanopore-based DNA sequencing, covering the long period of vegetative growth and transition to flowering in moso bamboo. We discovered that CHH methylation gradually accumulates from vegetative to reproductive growth in a time-dependent fashion. Differentially methylated regions, correlating with chronological aging, occurred preferentially at both transcription start sites and transcription termination sites. Genes with CG methylation changes showed an enrichment of Gene Ontology (GO) categories in 'vegetative to reproductive phase transition of meristem'. Combining methylation data with mRNA sequencing revealed that DNA methylation in promoters, introns and exons may have different roles in regulating gene expression. Finally, circular RNA (circRNA) sequencing revealed that the flanking introns of circRNAs are hypermethylated and enriched in long terminal repeat (LTR) retrotransposons. Together, the observations in this study provide insights into the dynamic DNA methylation and circRNA landscapes, correlating with chronological age, which paves the way to study further the impact of epigenetic factors on flowering in moso bamboo.

Transcriptome Profiling of Stem-Differentiating Xylem in Response to Abiotic Stresses Based on Hybrid Sequencing in Cunninghamia lanceolata.

Cunninghamia lanceolata (C. lanceolata) belongs to Gymnospermae, which are fast-growing and have desirable wood properties. However, C. lanceolata's stress resistance is little understood. To unravel the physiological and molecular regulation mechanisms under environmental stresses in the typical gymnosperm species of C. lanceolata, three-year-old plants were exposed to simulated drought stress (polyethylene glycol 8000), salicylic acid, and cold treatment at 4 °C for 8 h, 32 h, and 56 h, respectively. Regarding the physiological traits, we observed a decreased protein content and increased peroxidase upon salicylic acid and polyethylene glycol treatment. Superoxide dismutase activity either decreased or increased at first and then returned to normal under the stresses. Regarding the molecular regulation, we used both nanopore direct RNA sequencing and short-read sequencing to reveal a total of 5646 differentially expressed genes in response to different stresses, of which most had functions in lignin catabolism, pectin catabolism, and xylan metabolism, indicating that the development of stem-differentiating xylem was affected upon stress treatment. Finally, we identified a total of 51 AP2/ERF, 29 NAC, and 37 WRKY transcript factors in C. lanceolata. The expression of most of the NAC TFs increased under cold stress, and the expression of most of the WRKY TFs increased under cold and SA stress. These results revealed the transcriptomics responses in C. lanceolata to short-term stresses under this study's experimental conditions and provide preliminary clues about stem-differentiating xylem changes associated with different stresses.

Clinical features of multifocal papillary thyroid carcinoma and risk factors of cervical metastatic lymph nodes.

OBJECTIVE: To analyze the clinical features of multifocal papillary thyroid carcinoma (PTC) and the risk factors of cervical metastatic lymph nodes. METHODS: A total of 1524 patients with papillary thyroid carcinoma admitted in Gansu Provincial Cancer Hospital from January 2020 to August 2021 were enrolled, including 492 cases of multifocal PTC and 1032 cases of unifocal PTC. The clinicopathologic features of multifocal PTC and unifocal PTC were analyzed by comparing their differences in gender, ethnicity, age, body mass index, accompanying diabetes mellitus, accompanying hypertension, preoperative thyroid stimulating hormone and thyroglobulin levels, location of lesions, maximum diameter of lesions, sum of lesion diameters, central metastatic lymph nodes, lateral cervical metastatic lymph nodes, presence of Hashimoto's thyroiditis, and thyroid capsule invasion. Patients were also assessed according to the presence or absence of central metastatic lymph nodes and lateral cervical metastatic lymph nodes to understand clinicopathological parameter differences, and multivariate logistic regression analysis was used to explore the risk factors. RESULTS: Compared with unifocal PTC group, multifocal PTC group had significantly higher proportion of patients aged over 55 years, accompanying hypertension, central metastatic lymph nodes or cervical metastatic lymph nodes, Hashimoto's thyroiditis and capsule invasion (all P<0.05); 55.1% of patients with multifocal PTC had lesions distributed bilaterally, and the maximum diameter and diameter sum of the lesions were greater than those in unifocal PTC group (all P<0.01). Multivariate logistic regression analysis showed that male, maximum diameter of lesion more than 7 mm, capsular invasion were independent risk factors for central metastatic lymph nodes (all P<0.05); while male, maximum diameter of lesion more than 7 mm, preoperative thyroglobulin more than 55 ng/mL, and central metastatic lymph nodes were risk factors for lateral cervical metastatic lymph nodes in patients with multifocal PTC (all P<0.05). CONCLUSION: Patients with multifocal PTC have significantly higher central and lateral cervical metastatic lymph nodes, particularly for male patients with a maximum diameter of lesion more than 7 mm, invasion of capsule, and preoperative thyroglobulin more than 55 ng/mL.

Genome-wide profiling of circular RNAs, alternative splicing, and R-loops in stem-differentiating xylem of Populus trichocarpa.

Circular RNAs (circRNAs) are a recently discovered type of non-coding RNA derived from pre-mRNAs. R-loops consist of a DNA:RNA hybrid and the associated single-stranded DNA. In Arabidopsis thaliana, circRNA:DNA R-loops regulate alternative splicing (AS) of SEPALLATA3 (SEP3). However, the occurrence and functions of circRNAs and R-loops in Populus trichocarpa are largely unexplored. Here, we performed circRNA-enriched sequencing in the stem-differentiating xylem (SDX) of P. trichocarpa and identified 2,742 distinct circRNAs, including circ-CESA4, circ-IRX7, and circ-GUX1, which are generated from genes involved in cellulose, and hemicellulose biosynthesis, respectively. To investigate the roles of circRNAs in modulating alternative splicing (AS), we detected 7,836 AS events using PacBio Iso-Seq and identified 634 circRNAs that overlapped with 699 AS events. Furthermore, using DNA:RNA hybrid immunoprecipitation followed by sequencing (DRIP-seq), we identified 8,932 R-loop peaks that overlapped with 181 circRNAs and 672 AS events. Notably, several SDX-related circRNAs overlapped with R-loop peaks, pointing to their possible roles in modulating AS in SDX. Indeed, overexpressing circ-IRX7 increased the levels of R-loop structures and decreased the frequency of intron retention in linear IRX7 transcripts. This study provides a valuable R-loop atlas resource and uncovers the interplay between circRNAs and AS in SDX of P. trichocarpa.

Profiling of circular RNA N6 -methyladenosine in moso bamboo (Phyllostachys edulis) using nanopore-based direct RNA sequencing.

N6 -methyladenosine (m6 A) is a prevalent modification in messenger RNAs and circular RNAs that play important roles in regulating various aspects of RNA metabolism. However, the occurrence of the m6 A modification in plant circular RNAs has not been reported. A widely used method to identify m6 A modifications relies on m6 A-specific antibodies followed by next-generation sequencing of precipitated RNAs (MeRIP-Seq). However, one limitation of MeRIP-Seq is that it does not provide the precise location of m6 A at single-nucleotide resolution. Although more recent sequencing techniques such as Nanopore-based direct RNA sequencing (DRS) can overcome such limitations, the technology does not allow sequencing of circular RNAs, as these molecules lack a poly(A) tail. Here, we developed a novel method to detect the precise location of m6 A modifications in circular RNAs using Nanopore DRS. We first enriched our samples for circular RNAs, which we then fragmented and sequenced on the Nanopore platform with a customized protocol. Using this method, we identified 470 unique circular RNAs from DRS reads based on the back-spliced junction region. Among exonic circular RNAs, about 10% contained m6 A sites, which mainly occurred around acceptor and donor splice sites. This study demonstrates the utility of our antibody-independent method in identifying total and methylated circular RNAs using Nanopore DRS. This method has the additional advantage of providing the exact location of m6 A sites at single-base resolution in circular RNAs or linear transcripts from non-coding RNA without poly(A) tails.

The crosstalk between Sirt1 and Keap1/Nrf2/ARE anti-oxidative pathway forms a positive feedback loop to inhibit FN and TGF-ß1 expressions in rat glomerular mesangial cells.

Oxidative stress aroused by advanced glycation-end products (AGEs) is a culprit in the pathological progression of diabetic nephropathy. Both Sirt1 and the Keap1/Nrf2/ARE anti-oxidative pathway exert crucial inhibitory effects on the development of diabetic nephropathy. Our previous study has confirmed that Sirt1 activation can inhibit the upregulation of fibronectin (FN) and transforming growth factor-ß1 (TGF-ß1) by promoting Keap1/Nrf2/ARE pathway in glomerular mesangial cells (GMCs) challenged with AGEs. However, the underlying mechanism needs further investigation. Here, we found that concomitant with deacetylating and reducing the ubiquitination levels of Nrf2, Sirt1 significantly enhanced the activity of Keap1/Nrf2/ARE pathway including decreasing Keap1 expression, promoting the nuclear content, ARE-binding ability, and transcriptional activity of Nrf2, augmenting the protein levels of heme oxygenase 1, a target gene of Nrf2, which eventually quenched ROS overproduction and alleviating FN and TGF-ß1 accumulation in AGEs-treated GMCs. And depletion of Nrf2 blocked those renoprotective effects of Sirt1. Interestingly, Nrf2 also positively regulated Sirt1 at the protein expression and deacetylase activity levels as evidenced by tert-Butylhydroquinone and specific siRNA targeting Nrf2 to downregulate FN and TGF-ß1. In conclusion, the current study basically demonstrated that the crosstalk between Sirt1 and Keap1/Nrf2/ARE anti-oxidative pathway forms a positive feedback loop to inhibit the protein expressions of FN and TGF-ß1 in AGEs-treated GMCs.

Surface EMG-Based Inter-Session Gesture Recognition Enhanced by Deep Domain Adaptation.

High-density surface electromyography (HD-sEMG) is to record muscles' electrical activity from a restricted area of the skin by using two dimensional arrays of closely spaced electrodes. This technique allows the analysis and modelling of sEMG signals in both the temporal and spatial domains, leading to new possibilities for studying next-generation muscle-computer interfaces (MCIs). sEMG-based gesture recognition has usually been investigated in an intra-session scenario, and the absence of a standard benchmark database limits the use of HD-sEMG in real-world MCI. To address these problems, we present a benchmark database of HD-sEMG recordings of hand gestures performed by 23 participants, based on an 8 × 16 electrode array, and propose a deep-learning-based domain adaptation framework to enhance sEMG-based inter-session gesture recognition. Experiments on NinaPro, CSL-HDEMG and our CapgMyo dataset validate that our approach outperforms state-of-the-arts methods on intra-session and effectively improved inter-session gesture recognition.

Synthesis of Coumestrol and Aureol.

A total synthesis of coumestrol (1) and aureol (2) is described. The Perkin condensation of 2-bromo-4-hydroxylphenylacetic acid (6) and o-hydroxybenzaldehydes (7) gave the corresponding 2'-bromo-3-arylcoumarins (9). A copper-catalyzed consecutive hydroxylation and aerobic oxidative coupling of 9 under microwave conditions facilitated the total synthesis of 1 and 2, respectively, with spectroscopic data highly similar to those of natural products.

Rapid synthesis of isoquinolinones by intramolecular coupling of amides and ketones.

Amides and ketones were intramolecularly coupled in the presence of KOt-Bu/DMF. The reaction provided good yields of a variety of isoquinolinones. A reaction mechanism of radical addition and subsequent E2-elimination is proposed.