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The nuclear receptor corepressor (NCoR) forms a complex with histone deacetylase 3 (HDAC3) that mediates repressive functions of unliganded nuclear receptors and other transcriptional repressors by deacetylation of histone substrates. Recent studies provide evidence that NCoR/HDAC3 complexes can also exert coactivator functions in brown adipocytes by deacetylating and activating PPARγ coactivator 1α (PGC1α) and that signaling via receptor activator of nuclear factor kappa-B (RANK) promotes the formation of a stable NCoR/HDAC3/PGC1β complex that coactivates nuclear factor kappa-B (NFκB)- and activator protein 1 (AP-1)-dependent genes required for osteoclast differentiation. Here, we demonstrate that activation of Toll-like receptor (TLR) 4, but not TLR3, the interleukin 4 (IL4) receptor nor the Type I interferon receptor, also promotes assembly of an NCoR/HDAC3/PGC1β coactivator complex. Receptor-specific utilization of TNF receptor-associated factor 6 (TRAF6) and downstream activation of extracellular signal-regulated kinase 1 (ERK1) and TANK-binding kinase 1 (TBK1) accounts for the common ability of RANK and TLR4 to drive assembly of an NCoR/HDAC3/PGC1β complex in macrophages. ERK1, the p65 component of NFκB, and the p300 histone acetyltransferase (HAT) are also components of the induced complex and are associated with local histone acetylation and transcriptional activation of TLR4-dependent enhancers and promoters. These observations identify a TLR4/TRAF6-dependent signaling pathway that converts NCoR from a corepressor of nuclear receptors to a coactivator of NFκB and AP-1 that may be relevant to functions of NCoR in other developmental and homeostatic processes.

The nuclear receptor co-repressor (NCoR) complex mediates transcriptional repression dependent on histone deacetylation by histone deacetylase 3 (HDAC3) as a component of the complex. Unexpectedly, we found that signaling by the receptor activator of nuclear factor κB (RANK) converts the NCoR/HDAC3 co-repressor complex to a co-activator of AP-1 and NF-κB target genes that are required for mouse osteoclast differentiation. Accordingly, the dominant function of NCoR/HDAC3 complexes in response to RANK signaling is to activate, rather than repress, gene expression. Mechanistically, RANK signaling promotes RNA-dependent interaction of the transcriptional co-activator PGC1β with the NCoR/HDAC3 complex, resulting in the activation of PGC1β and inhibition of HDAC3 activity for acetylated histone H3. Non-coding RNAs Dancr and Rnu12, which are associated with altered human bone homeostasis, promote NCoR/HDAC3 complex assembly and are necessary for RANKL-induced osteoclast differentiation in vitro. These findings may be prototypic for signal-dependent functions of NCoR in other biological contexts.

This paper summarized the nursing practice of a patient with constipation after surgery of thoracic vertebra compression fracture treated by midnight-noon ebb-flow acupiont application combined with Chinese herbal medicine hot compress. Based on the comprehensive nursing assessment, targeted nursing interventions on pain, postoperative constipation, anxiety and potential complications were carried out. In addition, Traditional Chines medicine nursing techniques such as midnight-noon ebb-flow acupiont application combined with Chinese herbal medicine hot compress were conducted to relieve the constipation symptoms and improve the recovery of the patient. (本文总结子午流注择时穴位贴敷联合中药热奄包改善1例胸椎压缩性骨折术后患者便秘的护理体会。护理人员积极开展护理评估, 明确护理要点, 根据患者疼痛、便秘、焦虑、潜在并发症等主要问题进行护理干预, 并配合穴位贴敷、中药热奄包热敷等中医护理适宜技术, 改善患者便秘症状, 减轻疼痛, 促进其早期康复。)

Background & aimsMitochondrial dysfunction disrupts the synthesis and secretion of digestive enzymes in pancreatic acinar cells and plays a primary role in the etiology of exocrine pancreas disorders. However, the transcriptional mechanisms that regulate mitochondrial function to support acinar cell physiology are poorly understood. Here, we aim to elucidate the function of estrogen-related receptor γ (ERRγ) in pancreatic acinar cell mitochondrial homeostasis and energy production.MethodsTwo models of ERRγ inhibition, GSK5182-treated wild-type mice and ERRγ conditional knock-out (cKO) mice, were established to investigate ERRγ function in the exocrine pancreas. To identify the functional role of ERRγ in pancreatic acinar cells, we performed histologic and transcriptome analysis with the pancreas isolated from ERRγ cKO mice. To determine the relevance of these findings for human disease, we analyzed transcriptome data from multiple independent human cohorts and conducted genetic association studies for ESRRG variants in 2 distinct human pancreatitis cohorts.ResultsBlocking ERRγ function in mice by genetic deletion or inverse agonist treatment results in striking pancreatitis-like phenotypes accompanied by inflammation, fibrosis, and cell death. Mechanistically, loss of ERRγ in primary acini abrogates messenger RNA expression and protein levels of mitochondrial oxidative phosphorylation complex genes, resulting in defective acinar cell energetics. Mitochondrial dysfunction due to ERRγ deletion further triggers autophagy dysfunction, endoplasmic reticulum stress, and production of reactive oxygen species, ultimately leading to cell death. Interestingly, ERRγ-deficient acinar cells that escape cell death acquire ductal cell characteristics, indicating a role for ERRγ in acinar-to-ductal metaplasia. Consistent with our findings in ERRγ cKO mice, ERRγ expression was significantly reduced in patients with chronic pancreatitis compared with normal subjects. Furthermore, candidate locus region genetic association studies revealed multiple single nucleotide variants for ERRγ that are associated with chronic pancreatitis.ConclusionsCollectively, our findings highlight an essential role for ERRγ in maintaining the transcriptional program that supports acinar cell mitochondrial function and organellar homeostasis and provide a novel molecular link between ERRγ and exocrine pancreas disorders.

The enhanced recovery after surgery (ERAS)has been widely applied in the treatment of rehabilitation of patient with total knee arthroplasty (TKA). The ERAS has been proved to be effective in relieving pain, shortening the length of hospital stay, reducing economic and social healthcare costs. By reviewing literatures, this paper summarized the application of appropriate technology of Traditional Chinese and western medicine based on the concept of ERAS in TKA, and provided reference for improvement of perioperative nursing of TKA. (近年来, 加速康复外科(ERAS)理念在骨科全膝关节置换术(TKA)患者治疗和康复中得到了应用和普及, 基于ERAS的干预能够减轻患者痛苦, 缩短住院周期, 节约经济成本和社会医疗资源成本。本文通过文献搜索, 归纳总结基于ERAS理念的中西医结合护理干预在TKA围手术期中的应用, 旨在为提升TKA护理质量提供参考。)

Humanistic care has been considered a core element of high-quality nursing service. This paper summarized the practice of Humanistic nursing with characteristics of Traditional Chinese Medicine in the nursing ward rounds of a patient after total knee arthroplasty (TKA). Nursing ward rounds with characteristics of Traditional Chinese Medicine was conducted, and patient’s needs on pain control, relief of anxiety, prevention of compilations and functional exercise were analyzed before implementation of targeted interventions and humanistic care. It may help to improve nurse awareness and practice skills of humanistic nursing with characteristics of Traditional Chinese Medicine in the nursing ward rounds. (人文关怀属于优质护理服务范畴。本文总结l例人工全膝关节置换术后患者中医特色人文关怀护理查房经验, 通过开展具有中医特色的人文关怀护理查房, 分析患者术后疼痛、焦虑、并发症、饮食和功能锻炼需求并制定护理干预措施, 以缓解患者临床症状。该模式的对促进全院护理人员的关怀意识及能力提升具有积极意义。)

Spinocerebellar ataxia type 7 (SCA7) is a retinal-cerebellar degenerative disorder caused by CAG-polyglutamine (polyQ) repeat expansions in the ataxin-7 gene. As many SCA7 clinical phenotypes occur in mitochondrial disorders, and magnetic resonance spectroscopy of patients revealed altered energy metabolism, we considered a role for mitochondrial dysfunction. Studies of SCA7 mice uncovered marked impairments in oxygen consumption and respiratory exchange. When we examined cerebellar Purkinje cells in mice, we observed mitochondrial network abnormalities, with enlarged mitochondria upon ultrastructural analysis. We developed stem cell models from patients and created stem cell knockout rescue systems, documenting mitochondrial morphology defects, impaired oxidative metabolism, and reduced expression of nicotinamide adenine dinucleotide (NAD+) production enzymes in SCA7 models. We observed NAD+ reductions in mitochondria of SCA7 patient NPCs using ratiometric fluorescent sensors and documented alterations in tryptophan-kynurenine metabolism in patients. Our results indicate that mitochondrial dysfunction, stemming from decreased NAD+, is a defining feature of SCA7.

The PWWP domain of hepatoma‐derived growth factor‐related protein 2 (HDGFRP2) recognizes methylated histones to initiate the recruitment of homologous recombination repair proteins to damaged silent genes. The combined depletion of HDGFRP2 and its paralog PSIP1 effectively impedes the onset and progression of diffuse intrinsic pontine glioma (DIPG). Here, we discovered varenicline and 4‐(4‐bromo‐1H‐pyrazol‐3‐yl) pyridine (BPP) as inhibitors of the HDGFRP2 PWWP domain through a fragment‐based screening method. The complex crystal structures reveal that both Varenicline and BPP engage with the aromatic cage of the HDGFRP2 PWWP domain, albeit via unique binding mechanisms. Notably, BPP represents the first single‐digit micromolar inhibitor of the HDGFRP2 PWWP domain with a high ligand efficiency. As a dual inhibitor targeting both HDGFRP2 and PSIP1 PWWP domains, BPP offers an exceptional foundation for further optimization into a chemical tool to dissect the synergetic function of HDGFRP2 and PSIP1 in DIPG pathogenesis. [ABSTRACT FROM AUTHOR]

A strategy for cross‐dehydrogenative C(sp2)‐C(sp3) coupling was developed by direct and highly selective V‐catalyzed ortho‐aminomethylation of phenol with aniline derivatives. A series of aminomethylphenol compounds were obtained in moderate to good yields under mild reaction conditions and with a broad substrate scope. A possible radical mechanism was proposed, and it was found that the coordination of phenolic hydroxyl groups with V5+ was crucial for the effective activation of the ortho position. [ABSTRACT FROM AUTHOR]