Deposition of H2A.Z in chromatin is known to be mediated by a conserved SWR1 chromatin‐remodeling complex in eukaryotes. However, little is known about whether and how the SWR1 complex cooperates ...with other chromatin regulators. Using immunoprecipitation followed by mass spectrometry, we found all known components of the Arabidopsis thaliana SWR1 complex and additionally identified the following three classes of previously uncharacterized plant‐specific SWR1 components: MBD9, a methyl‐CpG‐binding domain‐containing protein; CHR11 and CHR17 (CHR11/17), ISWI chromatin remodelers responsible for nucleosome sliding; and TRA1a and TRA1b, accessory subunits of the conserved NuA4 histone acetyltransferase complex. MBD9 directly interacts with CHR11/17 and the SWR1 catalytic subunit PIE1, and is responsible for the association of CHR11/17 with the SWR1 complex. MBD9, TRA1a, and TRA1b function as canonical components of the SWR1 complex to mediate H2A.Z deposition. CHR11/17 are not only responsible for nucleosome sliding but also involved in H2A.Z deposition. These results indicate that the association of the SWR1 complex with CHR11/17 may facilitate the coupling of H2A.Z deposition with nucleosome sliding, thereby co‐regulating gene expression, development, and flowering time.
Synopsis
Cooperation of the SWR1 remodeler, responsible for histone H2A.Z deposition, with other chromatin regulators is incompletely understood. Here, proteomic identification of plant SWR1 complex components reveals its coupling to nucleosome sliding activities.
Characterization of the Arabidopsis SWR1 complex identifies CHR11, CHR17, TRA1A, TRA1B, and MBD9 as plant‐specific components.
ISWI remodeler catalytic subunits CHR11 and CHR17 associate with the SWR1 complex to couple nucleosome sliding and H2A.Z deposition.
MBD9 bridges CHR11 and CHR17 to the core SWR1 complex.
Together with other SWR1 components, MBD9 and CHR11/17 co‐regulate gene expression, development, and flowering time.
Proteomic analysis of Arabidopsis thaliana SWR1 complex components implicates nucleosome‐sliding ISWI remodeler subunits CHR11 and CHR17 also in histone deposition.
Objectives
The therapeutic effect of acupuncture treatments (AT) on functional gastrointestinal disorders (FGIDs) is contentious. A meta‐analysis was conducted to assess the efficacy and safety of ...acupuncture for FGIDs.
Methods
The Cochrane Library, EMBASE, PUBMED, Web of Science, Wanfang Database, China National Knowledge Infrastructure, and VIP Database were searched through December 31, 2019 with no language restrictions. Risk ratio (RR) with 95% confidence interval (CI) was calculated to determine the improvement in symptom severity after treatment.
Results
A total of 61 randomized controlled trials (RCTs) on FGIDs were included. The pooled results illustrated the following: compared to pharmacotherapy (RR 1.13, 95% CI 1.09–1.17), placebo acupuncture (RR 1.69, 95% CI 1.37–2.08), no specific treatment (RR 1.86, 95% CI 1.31–2.62), and AT as an adjuvant intervention to other active treatments (RR 1.25, 95% CI 1.21–1.30), AT had more favorable improvements in symptom severity; sub‐group analysis results classified according to functional dyspepsia, irritable bowel syndrome, and functional constipation also supported this finding; and the incidence of adverse events was lower in AT than in other treatments (RR 0.75, 95% CI 0.56–0.99).
Conclusions
This meta‐analysis found that AT was significantly associated with relief of FGIDs symptoms; however, the evidence level was moderate or low. Further data from rigorously designed and well powered RCTs are needed to verify the effectiveness and safety of AT as a FGIDs treatment.
PROSPERO PROTOCOL NUMBER: CRD42020169508.
There exist differences in the epidemiological characteristics, clinicopathological features, tumor biological characteristics, treatment patterns, and drug selections between gastric cancer patients ...from the Eastern and Western countries. The Chinese Society of Clinical Oncology (CSCO) has organized a panel of senior experts specializing in all sub‐specialties of gastric cancer to compile a clinical guideline for the diagnosis and treatment of gastric cancer since 2016 and renews it annually. Taking into account regional differences, giving full consideration to the accessibility of diagnosis and treatment resources, these experts have conducted expert consensus judgment on relevant evidence and made various grades of recommendations for the clinical diagnosis and treatment of gastric cancer to reflect the value of cancer treatment and meeting health economic indexes in China. The 2021 CSCO Clinical Practice Guidelines for Gastric Cancer covers the diagnosis, treatment, follow‐up, and screening of gastric cancer. Based on the 2020 version of the CSCO Chinese Gastric Cancer guidelines, this updated guideline integrates the results of major clinical studies from China and overseas for the past year, focused on the inclusion of research data from the Chinese population for more personalized and clinically relevant recommendations. For the comprehensive treatment of non‐metastatic gastric cancer, attentions were paid to neoadjuvant treatment. The value of perioperative chemotherapy is gradually becoming clearer and its recommendation level has been updated. For the comprehensive treatment of metastatic gastric cancer, recommendations for immunotherapy were included, and immune checkpoint inhibitors from third‐line to the first‐line of treatment for different patient groups with detailed notes are provided.
The Chinese Society of Clinical Oncology (CSCO) organized a panel of senior experts specializing in all sub‐specialties of gastric cancer to compile the clinical guideline for gastric cancer in 2016 and then renewed it every year. The 2021 CSCO Clinical Practice Guidelines for gastric cancer covered the diagnosis, treatment, follow‐up and screening.
Despite very different functions, studies increasingly report that there may be a potential central nervous anatomical connection between the heart and the small intestine. In this study, the central ...nervous anatomical relationship between the heart and small intestine was studied via a viral tracer. Pseudorabies virus (PRV) syngeneic strains with different fluorescent reporter genes (eGFP or mRFP) were microinjected into the heart walls and small intestinal walls of male C57BL/6J using glass microelectrode. The results showed that the co-labeled nuclei in the brain were lateral periaqueductal gray (LPAG) and ventrolateral periaqueductal gray (VLPAG) in the midbrain, mesencephalic trigeminal nucleus (Me5), and motor trigeminal nucleus anterior digastric Part (5Adi) in the pons. The co-labeled sites in the spinal cord were intermediolateral column (IML) in the second thoracic vertebra, IML and lamina 7 of the spinal gray (7SP) in the third thoracic vertebra, and IML in the fourth thoracic vertebra. Our data show that there is a neuroanatomical connection between the small intestine and the heart in the central nervous system (CNS). Neuroanatomical integration of the heart and small intestine may provide a basis for revealing the physiological and pathological interactions between the circulatory and digestive systems. The interactions may be mediated more effectively through sympathetic nerves.
A color change: X‐ray‐induced photochromic species are rare and can be used for detection of X‐rays. A highly robust X‐ray‐sensitive material with the discrete structure of a metal–organic complex ...has been found to show both soft and hard X‐ray‐induced photochromism at room temperature (see picture). A new ligand‐to‐ligand electron‐transfer mechanism was proposed to elucidate this photochromic phenomenon.
Background： Functional magnetic resonance imaging （fMRI） is a novel method for studying the changes of brain networks due to acupuncture treatment. In recent years, more and more studies have focused ...on the brain functional connectivity network of acupuncture stimulation. Objective： To offer an overview of the different influences of acupuncture on the brain functional connec- tivity network from studies using resting-state fMRI. Search strategy： The authors performed a systematic search according to PRISMA guidelines, The database PubMed was searched from January 1, 2006 to December 31, 2016 with restriction to human studies in English language. Inclusion criteria： Electronic searches were conducted in PubMed using the keywords ＂acupuncture＂ and ＂neuroimaging＂ or ＂resting-state fMRI＂ or ＂functional connectivity＂, Data extraction and analysis： Selection of included articles, data extraction and methodological quality assessments were respectively conducted by two review authors. Results： Forty-four resting-state fMRI studies were included in this systematic review according to inclu- sion criteria. Thirteen studies applied manual acupuncture vs. sham, four studies applied electro- acupuncture vs. sham, two studies also compared transcutaneous electrical acupoint stimulation vs. sham, and nine applied sham acupoint as control. Nineteen studies with a total number of 574 healthy subjects selected to perform fMRI only considered healthy adult volunteers. The brain functional connec- tivity of the patients had varying degrees of change. Compared with sham acupuncture, verum acupunc- ture could increase default mode network and sensorimotor network connectivity with pain-, affective- and memory-related brain areas. It has significantly greater connectivity of genuine acupuncture between the periaqueductal gray, anterior cingulate cortex, left posterior cingulate cortex, right anterior insula, limbic/paralimbic and precuneus compared with sham acupuncture. Some research had also shown that acupuncture could adjust the limbic-paralimbic-neocortical network, brainstem, cerebellum, subcortical and hippocampus brain areas. Conclusion： It can be presumed that the functional connectivity network is closely related to the mech- anism of acupuncture, and central integration plays a critical role in the acupuncture mechanism.
Premature senescence is a key process in the progression of diabetic nephropathy (DN). In our study, we hypothesized that receptors for advanced glycation end-products (RAGE) mediate endoplasmic ...reticulum (ER) stress to induce premature senescence via p21 signaling activation in diabetic nephropathy. Here, we demonstrated that elevated expression of RAGE, ER stress marker glucose-regulated protein 78 (GRP78), and cell-cycle regulator p21 was all positively correlated with enhanced senescence-associated-β-galactosidase (SA-β-gal) activity in DN patients. In addition, the fraction of SA-β-gal or cells in the G0G1 phase were enhanced in cultured mouse proximal tubular epithelial cells (PTECs) and the expression of RAGE, GRP78 and p21 was up-regulated by advanced glycation end-products (AGEs) in a dose- and time-dependent manner. Interestingly, ER stress inducers or RAGE overexpression mimicked AGEs induced-premature senescence, and this was significantly suppressed by p21 gene silencing. However, RAGE blocking successfully attenuated AGEs-induced ER stress and p21 expression, as well as premature senescence. Moreover, ER stress inducers directly caused p21 activation, premature senescence, and also enhanced RAGE expression by positive feedback. These observations suggest that RAGE promotes premature senescence of PTECs by activation of ER stress-dependent p21 signaling.
Note: We demonstrated that elevated expression of RAGE, GRP78 and p21 was all positively correlated with enhanced SA-β-gal activity in DN patients. In addition, the fraction of SA-β-gal or cells in the G0G1 phase were enhanced in cultured mouse PTECs; and the expression of RAGE, GRP78 and p21 was up-regulated by AGEs in a dose- and time-dependent manner. Interestingly, ER stress inducers or RAGE overexpression mimicked AGEs induced-premature senescence, and this was significantly suppressed by p21 gene silencing. However, RAGE blocking successfully attenuated AGEs induced ER stress and p21 expression, as well as premature senescence. Moreover, ER stress inducers directly cause p21 activation and premature senescence, and also enhanced RAGE expression via positive feedback. These observations suggest that RAGE promotes premature senescence of PTECs via activation of ER stress-dependent p21 signaling. Display omitted
•RAGE and ER stress were positively correlated with premature senescence.•ER stress inducers or RAGE overexpression mimicked the premature senescence.•ER stress or RAGE inhibition led to reduction of p21 and premature senescence.•ER stress induced premature senescence by p21 signaling activation.
Premature senescence is an important event during diabetic nephropathy (DN) progression. Here, we investigated the role of endoplasmic reticulum (ER) stress-regulated activation of transcription ...factor 4 (ATF4)/p16 signaling in the premature senescence of renal tubular epithelial cells (RTECs) during DN development. In the renal tissues of Type 2 DN patients, we detected an increased number of senescent cells; elevated deposition of advanced glycation end products (AGEs); upregulated expression of ER stress marker, glucose-regulated protein 78; as well as overexpression of ATF4 and p16. Similarly, these phenomena were also observed in cultured mouse RTECs following AGE treatment. Interestingly, AGE-induced p16 expression and premature senescence were successfully attenuated by ER stress inhibitor and ATF4 gene silencing. Moreover, AGE-induced premature senescence was mimicked by ER stress inducers and ATF4 overexpression, while suppressed by p16 gene silencing. In addition, ER stress inducers can augment ATF4 expression. Therefore, our results demonstrate that the ER stress-regulated ATF4/p16 pathway is involved in the premature senescence of RTECs during DN progression.
Summary
Small interfering RNAs (siRNAs) are responsible for establishing and maintaining DNA methylation through the RNA‐directed DNA methylation (RdDM) pathway in plants. Although siRNA biogenesis ...is well known, it is relatively unclear about how the process is regulated. By a forward genetic screen in Arabidopsis thaliana, we identified a mutant defective in NOT1 and demonstrated that NOT1 is required for transcriptional silencing at RdDM target genomic loci. We demonstrated that NOT1 is required for Pol IV‐dependent siRNA accumulation and DNA methylation at a subset of RdDM target genomic loci. Furthermore, we revealed that NOT1 is a constituent of a multi‐subunit CCR4‐NOT deadenylase complex by immunoprecipitation combined with mass spectrometry and demonstrated that the CCR4‐NOT components can function as a whole to mediate chromatin silencing. Therefore, our work establishes that the CCR4‐NOT complex regulates the biogenesis of Pol IV‐dependent siRNAs, and hence facilitates DNA methylation and transcriptional silencing in Arabidopsis.
Significance Statement
The study identifies a mutant defective in NOT1 by a forward genetic screen and demonstrates that NOT1 is required for Pol IV‐dependent siRNA accumulation and DNA methylation and thereby facilitate chromatin silencing at a subset of RdDM target genomic loci. Because NOT1 is the largest subunit of the CCR4‐NOT complex responsible for mRNA deadenylation, the study reveals a potential role for RNA deadenylation in siRNA production.
Myocardial ischemia-reperfusion can further exacerbate myocardial injury and increase the risk of death. Our previous research found that the paraventricular nucleus (PVN) of the hypothalamus plays a ...crucial role in the improvement of myocardial ischemia-reperfusion injury (MIRI) by electroacupuncture (EA) pretreatment, but its mechanism of action is still unclear. CRH neurons exhibit periodic concentrated expression in PVN, but further research is needed to determine whether they are involved in the improvement of MIRI by EA pretreatment. Meanwhile, numerous studies have shown that changes in sympathetic nervous system innervation and activity are associated with many heart diseases. This study aims to investigate whether EA pretreatment improves MIRI through sympathetic nervous system mediated by PVN
neurons.
Integrated use of fiber-optic recording, chemical genetics and other methods to detect relevant indicators: ECG signals were acquired through Powerlab standard II leads, and LabChart 8 calculated heart rate, ST-segment offset, and heart rate variability (HRV); Left ventricular ejection fraction (LVEF), left ventricular short-axis shortening (LVFS), left ventricular end-systolic internal diameter (LVIDs) and interventricular septal thickness (IVSs) were measured by echocardiography; Myocardial infarct area (IA) and area at risk (AAR) were calculated by Evans-TTC staining. Pathological changes in cardiomyocytes were observed by HE staining; Changes in PVN
neuronal activity were recorded by fiber-optic photometry; Sympathetic nerve discharges were recorded for in vivo electrophysiology; NE and TH protein expression was assayed by Western blot.
Our data indicated that EA pretreatment can effectively alleviate MIRI. Meanwhile, we found that in the MIRI model, the number and activity of CRH neurons co labeled with c-Fos in the PVN area of the rat brain increased, and the frequency of sympathetic nerve discharge increased. EA pretreatment could reverse this change. In addition, the results of chemical genetics indicated that inhibiting PVN
neurons has a similar protective effect on MIRI as EA pretreatment, and the activation of PVN
neurons can counteract this protective effect.
EA pretreatment can inhibit PVN
neurons and improve MIRI by inhibiting sympathetic nerve, which offers fresh perspectives on the application of acupuncture in the management of cardiovascular disease.
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