Non-coding 7S RNA inhibits transcription via mitochondrial RNA polymerase dimerization.

The mitochondrial genome encodes 13 components of the oxidative phosphorylation system, and altered mitochondrial transcription drives various human pathologies. A polyadenylated, non-coding RNA molecule known as 7S RNA is transcribed from a region immediately downstream of the light strand promoter in mammalian cells, and its levels change rapidly in response to physiological conditions. Here, we report that 7S RNA has a regulatory function, as it controls levels of mitochondrial transcription both in vitro and in cultured human cells. Using cryo-EM, we show that POLRMT dimerization is induced by interactions with 7S RNA. The resulting POLRMT dimer interface sequesters domains necessary for promoter recognition and unwinding, thereby preventing transcription initiation. We propose that the non-coding 7S RNA molecule is a component of a negative feedback loop that regulates mitochondrial transcription in mammalian cells.

The human mitochondrial genome contains a second light strand promoter.

The human mitochondrial genome must be replicated and expressed in a timely manner to maintain energy metabolism and supply cells with adequate levels of adenosine triphosphate. Central to this process is the idea that replication primers and gene products both arise via transcription from a single light strand promoter (LSP) such that primer formation can influence gene expression, with no consensus as to how this is regulated. Here, we report the discovery of a second light strand promoter (LSP2) in humans, with features characteristic of a bona fide mitochondrial promoter. We propose that the position of LSP2 on the mitochondrial genome allows replication and gene expression to be orchestrated from two distinct sites, which expands our long-held understanding of mitochondrial gene expression in humans.

Enhanced IFN Sensing by Aggressive Chronic Lymphocytic Leukemia Cells.

Type I IFN is made by cells in response to stress. Cancer cells exist in a state of stress, but their IFN response is complex and not completely understood. This study investigated the role of autocrine IFN in human chronic lymphocytic leukemia (CLL) cells. CLL cells were found to make low amounts of IFN via TANK-binding kinase 1 pathways, but p-STAT1 and -STAT2 proteins along with IFN-stimulated genes that reflect IFN activation were variably downregulated in cultured CLL cells by the neutralizing IFNAR1 Ab anifrolumab. Patients with CLL were segregated into two groups based on the response of their leukemia cells to anifrolumab. Samples associated with more aggressive clinical behavior indicated by unmutated IGHV genes along with high CD38 and p-Bruton's tyrosine kinase expression exhibited responses to low amounts of IFN that were blocked by anifrolumab. Samples with more indolent behavior were unaffected by anifrolumab. Hypersensitivity to IFN was associated with higher expression of IFNAR1, MX1, STAT1, and STAT2 proteins and lower activity of negative regulatory tyrosine phosphatases. Autocrine IFN protected responsive CLL cells from stressful tissue culture environments and therapeutic drugs such as ibrutinib and venetoclax in vitro, in part by upregulating Mcl-1 expression. These findings suggest hypersensitivity to IFN may promote aggressive clinical behavior. Specific blockade of IFN signaling may improve outcomes for patients with CLL with higher-risk disease.

Towards more precise automatic analysis: a systematic review of deep learning-based multi-organ segmentation.

Accurate segmentation of multiple organs in the head, neck, chest, and abdomen from medical images is an essential step in computer-aided diagnosis, surgical navigation, and radiation therapy. In the past few years, with a data-driven feature extraction approach and end-to-end training, automatic deep learning-based multi-organ segmentation methods have far outperformed traditional methods and become a new research topic. This review systematically summarizes the latest research in this field. We searched Google Scholar for papers published from January 1, 2016 to December 31, 2023, using keywords "multi-organ segmentation" and "deep learning", resulting in 327 papers. We followed the PRISMA guidelines for paper selection, and 195 studies were deemed to be within the scope of this review. We summarized the two main aspects involved in multi-organ segmentation: datasets and methods. Regarding datasets, we provided an overview of existing public datasets and conducted an in-depth analysis. Concerning methods, we categorized existing approaches into three major classes: fully supervised, weakly supervised and semi-supervised, based on whether they require complete label information. We summarized the achievements of these methods in terms of segmentation accuracy. In the discussion and conclusion section, we outlined and summarized the current trends in multi-organ segmentation.

The Potential of Berberine to Target Telocytes in Rabbit Heart.

A brand-new class of interstitial cells, called telocytes, has been detected in the heart. Telocytes can connect and transmit signals to almost all cardiomyocytes; this is highly interrelated with the occurrence and development of heart diseases. Modern studies have shown that berberine has a therapeutic effect on cardiovascular health. However, berberine's mechanism of action on the cardiovascular system through cardiac telocytes is unclear. Interestingly, 5 µm of berberine remarkably decreased the concentration of intracellular calcium and membrane depolarization in cultured telocytes, upregulated the expression of CX43 and ß-catenin, and downregulated the expressions of TRPV4 and TRPV1. Here, telocytes were identified in the vascular adventitia and intima, endocardium, myocardium, adventitia, and heart valves. Moreover, telocytes were broadly dispersed around cardiac vessels and interacted directly through gap junctions and indirectly through extracellular vesicles. Together, cardiac telocytes interact with berberine and then deliver drug information to the heart. Telocytes may be an essential cellular target for drug therapy of the cardiovascular system.

TXNIP deficiency attenuates renal fibrosis by modulating mTORC1/TFEB-mediated autophagy in diabetic kidney disease.

Thioredoxin-interacting protein (TXNIP) is an important regulatory protein for thioredoxin (TRX) that elicits the generation of reactive oxygen species (ROS) by inhibiting the redox function of TRX. Abundant evidence suggests that TXNIP is involved in the fibrotic process of diabetic kidney disease (DKD). However, the potential mechanism of TXNIP in DKD is not yet well understood. In this study, we found that TXNIP knockout suppressed renal fibrosis and activation of mammalian target of rapamycin complex 1 (mTORC1) and restored transcription factor EB (TFEB) and autophagy activation in diabetic kidneys. Simultaneously, TXNIP interference inhibited epithelial-to-mesenchymal transformation (EMT), collagen I and fibronectin expression, and mTORC1 activation, increased TFEB nuclear translocation, and promoted autophagy restoration in HK-2 cells exposed to high glucose (HG). Rapamycin, an inhibitor of mTORC1, increased TFEB nuclear translocation and autophagy in HK-2 cells under HG conditions. Moreover, the TFEB activators, curcumin analog C1 and trehalose, effectively restored HG-induced autophagy, and abrogated HG-induced EMT and collagen I and fibronectin expression in HK-2 cells. Taken together, these findings suggest that TXNIP deficiency ameliorates renal fibrosis by regulating mTORC1/TFEB-mediated autophagy in diabetic kidney diseases.

Effects of evidence-based nursing on surgical site wound infections in patients undergoing surgery for liver cancer: A meta-analysis.

This study aimed to systematically evaluate the impact of evidence-based nursing (EBN) on perioperative wound infections and postoperative complications in patients undergoing surgery for liver hepatocellular carcinoma (LIHC). Randomised controlled trials (RCTs) on the application of EBN on patients receiving LIHC surgery were searched in PubMed, Web of Science, Cochrane Library, Embase, Wanfang, China Biomedical Literature Database and China National Knowledge Infrastructure from the inception of each database to September 2023. Studies were screened and evaluated by two investigators based on inclusion and exclusion criteria, and data were extracted from the final included literature. RevMan 4.0 was used for data analysis. Overall, 15 RCTs involving 1374 patients with LIHC were included, with 687 in the EBN group and 687 in the conventional care group. The analysis revealed that the incidence of wound infections (odds ratio [OR] = 0.32, 95% confidence interval [CI]: 0.18-0.56, p < 0.001) and postoperative complications (OR = 0.22, 95% CI: 0.15-0.31, p < 0.001) was significantly lower in the EBN group than in the conventional care group. The available evidence suggests that nursing strategies for EBN applied in the perioperative period in patients with LIHC receiving surgery can effectively reduce the incidence of wound infections and postoperative complications and promote postoperative recovery.

Predicting Lymph Node Metastasis From Primary Cervical Squamous Cell Carcinoma Based on Deep Learning in Histopathologic Images.

We developed a deep learning framework to accurately predict the lymph node status of patients with cervical cancer based on hematoxylin and eosin-stained pathological sections of the primary tumor. In total, 1524 hematoxylin and eosin-stained whole slide images (WSIs) of primary cervical tumors from 564 patients were used in this retrospective, proof-of-concept study. Primary tumor sections (1161 WSIs) were obtained from 405 patients who underwent radical cervical cancer surgery at the Fudan University Shanghai Cancer Center (FUSCC) between 2008 and 2014; 165 and 240 patients were negative and positive for lymph node metastasis, respectively (including 166 with positive pelvic lymph nodes alone and 74 with positive pelvic and para-aortic lymph nodes). We constructed and trained a multi-instance deep convolutional neural network based on a multiscale attention mechanism, in which an internal independent test set (100 patients, 228 WSIs) from the FUSCC cohort and an external independent test set (159 patients, 363 WSIs) from the Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma cohort of the Cancer Genome Atlas program database were used to evaluate the predictive performance of the network. In predicting the occurrence of lymph node metastasis, our network achieved areas under the receiver operating characteristic curve of 0.87 in the cross-validation set, 0.84 in the internal independent test set of the FUSCC cohort, and 0.75 in the external test set of the Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma cohort of the Cancer Genome Atlas program. For patients with positive pelvic lymph node metastases, we retrained the network to predict whether they also had para-aortic lymph node metastases. Our network achieved areas under the receiver operating characteristic curve of 0.91 in the cross-validation set and 0.88 in the test set of the FUSCC cohort. Deep learning analysis based on pathological images of primary foci is very likely to provide new ideas for preoperatively assessing cervical cancer lymph node status; its true value must be validated with cervical biopsy specimens and large multicenter datasets.

An artificial intelligence-driven image quality assessment system for whole-body [18F]FDG PET/CT.

PURPOSE: Image quality control is a prerequisite for applying PET/CT. This study aimed to develop an artificial intelligence-driven real-time and accurate whole-body [18F]FDG PET/CT image quality assessment system. METHODS: This study included 173 patients (age, 59 ± 12 years; 66.3% males) with whole-body [18F]FDG PET/CT imaging. Images of ten patients were used as an educational set. Images of the rest 163 patients were reconstructed to 952 images by simulating several scanning times and randomly split into training (60%, 98 patients, 578 images), validation (20%, 33 patients, 192 images), and test (20%, 32 patients,182 images) sets. Two experienced physicians (R1 and R2) independently assessed the image quality of thorax, abdomen, and pelvis region twice (R1a and b; R2a and b), 1 month apart, using a 5-point Likert scale. Objective image quality metrics were extracted from the mediastinal blood pool, three liver levels, and the bilateral gluteus maximus. The developed convolutional neural networks for image quality assessment (IQA-CNNs) generated the subjective quality scores and objective image metrics. The IQA-CNNs and physicians' performances were compared for localization accuracy, score agreement, and process time. RESULTS: The physicians demonstrated good inter- and intra-rater subjective assessment agreement, with kappa coefficients (R1a vs. R2a, R1a vs. R1b, R2a vs. R2b, and R1a vs. R2b) of 0.78, 0.77, 0.76, and 0.80. The IQA-CNNs and R1 or R2 agreed in the subjective assessments, with kappa coefficients of 0.79 and 0.78. IQA-CNNs and R1 or R2 also agreed in their objective image quality assessment (ICC > 0.60). The IQA-CNNs evaluation speed was 200 times faster than the manual assessment. CONCLUSION: An automated system for rapid assessment of [18F]FDG PET/CT image quality was developed, showing comparable performance to senior physicians. The system generates a comprehensive and detailed image quality assessment report, including subjective visual scores and objective image metrics for various anatomical regions.

Yeast mismatch repair components are required for stable inheritance of gene silencing.

Alterations in epigenetic silencing have been associated with ageing and tumour formation. Although substantial efforts have been made towards understanding the mechanisms of gene silencing, novel regulators in this process remain to be identified. To systematically search for components governing epigenetic silencing, we developed a genome-wide silencing screen for yeast (Saccharomyces cerevisiae) silent mating type locus HMR. Unexpectedly, the screen identified the mismatch repair (MMR) components Pms1, Mlh1, and Msh2 as being required for silencing at this locus. We further found that the identified genes were also required for proper silencing in telomeres. More intriguingly, the MMR mutants caused a redistribution of Sir2 deacetylase, from silent mating type loci and telomeres to rDNA regions. As a consequence, acetylation levels at histone positions H3K14, H3K56, and H4K16 were increased at silent mating type loci and telomeres but were decreased in rDNA regions. Moreover, knockdown of MMR components in human HEK293T cells increased subtelomeric DUX4 gene expression. Our work reveals that MMR components are required for stable inheritance of gene silencing patterns and establishes a link between the MMR machinery and the control of epigenetic silencing.

Cellular Evidence for Telocytes Mediating Electroacupuncture to Ameliorate Obesity in Mice.

Electroacupuncture has been generally applied to target obesity, the principle of which is based on the meridian in traditional Chinese medicine. Although Telocytes (TCs) have been reported as the potential essence of meridians, their specific role in the electroacupuncture treatment of obesity remains unclear. Thus, we investigated the cellular evidence for TC-mediated electroacupuncture to alleviate obesity. Mice were divided into three groups as follows: electroacupuncture group (EA), control group (CG), and normal group (NG). The present study showed that the weight of perirenal white adipose tissue (rWAT), the serum level of total cholesterol, and the low-density lipoprotein cholesterol were all significantly decreased after electroacupuncture. Ultrastructurally, the prolongations (telopodes, Tps) of TCs were in direct contact with adipocytes, and lipid droplets were distributed on the surface of Tps. The proportions of double-positive fluorescent areas of TCs (CD34 and PDGFRα) were significantly elevated with concomitant elongated Tps in EA mice, as compared to those in CG mice. The expression of Cx43 and CD63 (gap junction and exosome markers) was significantly enhanced. These characteristics facilitated the transmission of electroacupuncture stimulation from skin to rWAT. We conclude that electroacupuncture relieved obesity by activating TCs morphologically, upregulating the gap junctions between TCs, and increasing the exosomes around TCs.

The Cellular Mechanism of Acupuncture for Ulcerative Colitis based on the Communication of Telocytes.

Acupuncture can ameliorate or treat diseases according to the meridian theory in traditional Chinese medicine (TCM); however, its mechanism has not been scientifically clarified. On the other hand, telocytes (TCs) are morphologically in accordance with the meridian system, which needs further cytological investigations and acupuncture confirmation. The present study showed that acupuncture could activate TCs in several ways, alleviating rabbit ulcerative colitis. TCs could cytologically communicate the acupoints, the acupuncture sites in skin with their corresponding large intestine by TC homo-cellular junctions, exosomes around TCs, and TC-mediated nerves or blood vessels. TCs expressed transient receptor potential vanilloid type 4, the mechanosensitive channel protein that can transduce the mechanical stimulation of acupuncture into biochemical signals transferring along the extremely thin and long TCs. Collectively, a cellular mechanism diagram of acupuncture was concluded based on TC characteristics. Those results also confirmed the viewpoint that TCs were the key cells of meridian essence in TCM.

Tembusu Virus entering the central nervous system caused nonsuppurative encephalitis without disrupting the blood-brain barrier.

Tembusu Virus (TMUV) is an emerging and re-emerging zoonotic pathogen that adversely affects poultry industry in recent years. TMUV disease is characterized by nonsuppurative encephalitis in ducklings. The duckling infection model was established to study the mechanism of TMUV crossing the blood-brain barrier (BBB) into the central nervous system (CNS). Here, we showed that no obvious clinical symptoms and enhancement of BBB permeability occurred at the early stage of infection (3∼5 dpi). While simultaneously virus particles were observed by transmission electron microscopy in the brain, inducing the accumulation of inflammatory cytokines. Neurological symptoms and disruption of BBB appeared at the intermediate stage of infection (7∼9 dpi). It was confirmed that TMUV could survive and propagate in brain microvascular endothelial cells (BMECs), but did not affect the permeability of BBB in vivo and in vitro at an early date. In conclusion, TMUV enters the CNS then causes encephalitis, and finally destruct the BBB, which may be due to the direct effect of TMUV on BMECs and the subsequent response of "inflammatory storm".IMPORTANCE The TMUV disease has caused huge losses to the poultry industry in Asia, which is potentially harmful to public health. Neurological symptoms and their sequelae are the main characters of this disease. However, the mechanism of how this virus enters the brain and causes encephalitis is unclear. In this study, we confirmed that the virus entered the CNS and then massively destroyed BBB and the BBB damage was closely associated with the subsequent outbreak of inflammation. TMUV may enter the CNS through the transcellular and "Trojan horse" pathways. These findings can fill the knowledge gap in the pathogenesis of TMUV-infected poultry and be benefit for the treatment of TMUV disease. What's more, TMUV is a representative to study the infection of avian flavivirus. Therefore, our studies have significances both for understanding of the full scope of mechanisms of TMUV and other flavivirus infection, and conceivably, for therapeutics.

NAD(P)H: quinone oxidoreductase 1 attenuates oxidative stress and apoptosis by regulating Sirt1 in diabetic nephropathy.

BACKGROUND: Diabetic nephropathy (DN) is one of the main complications of diabetes, and oxidative stress plays an important role in its progression. NAD(P)H: quinone oxidoreductase 1 (NQO1) protects cells from oxidative stress and toxic quinone damage. In the present study, we aimed to investigate the protective effects and underlying mechanisms of NQO1 on diabetes-induced renal tubular epithelial cell oxidative stress and apoptosis. METHODS: In vivo, the kidneys of db/db mice, which are a type 2 diabetes model, were infected with adeno-associated virus to induce NQO1 overexpression. In vitro, human renal tubular epithelial cells (HK-2 cells) were transfected with NQO1 pcDNA3.1(+) and cultured in high glucose (HG). Gene and protein expression was assessed by quantitative real-time PCR, western blotting, immunofluorescence analysis, and immunohistochemical staining. Reactive oxygen species (ROS) were examined by MitoSox red and flow cytometry. TUNEL assays were used to measure apoptosis. RESULT: In vivo, NQO1 overexpression reduced the urinary albumin/creatinine ratio (UACR) and blood urea nitrogen (BUN) level in db/db mice. Our results revealed that NQO1 overexpression could significantly increase the ratio of NAD+/NADH and silencing information regulator 1 (Sirt1) expression and block tubular oxidative stress and apoptosis in diabetic kidneys. In vitro, NQO1 overexpression reduced the generation of ROS, NADPH oxidase 1 (Nox1) and Nox4, the Bax/Bcl-2 ratio and the expression of Cleaved Caspase-3 and increased NAD+/NADH levels and Sirt1 expression in HK-2 cells under HG conditions. However, these effects were reversed by the Sirt1 inhibitor EX527. CONCLUSIONS: All these data suggest that NQO1 has a protective effect against oxidative stress and apoptosis in DN, which may be mediated by the regulation of Sirt1 through increasing intracellular NAD+/NADH levels. Therefore, NQO1 may be a new therapeutic target for DN.

Sestrin2 attenuates renal damage by regulating Hippo pathway in diabetic nephropathy.

Glomerular mesangial cell proliferation and extracellular matrix accumulation contribute to the progression of diabetic nephropathy (DN). As a conserved stress-inducible protein, sestrin2 (Sesn2) plays critical role in the regulation of oxidative stress, inflammation, autophagy, metabolism, and endoplasmic reticulum stress. In this study, we investigated the role of Sesn2 on renal damage in diabetic kidney using transgenic mice overexpressing Sesn2 and the effect of Sesn2 on mesangial cell proliferation and extracellular matrix accumulation in diabetic conditions and the possible molecular mechanisms involved. Sesn2 overexpression improved renal function and decreased glomerular hypertrophy, albuminuria, mesangial expansion, extracellular matrix accumulation, and TGF-ß1 expression, as well as oxidative stress in diabetic mice. In vitro experiments, using human mesangial cells (HMCs), revealed that Sesn2 overexpression inhibited high glucose (HG)-induced proliferation, fibronectin and collagen IV production, and ROS generation. Meanwhile, Sesn2 overexpression restored phosphorylation levels of Lats1 and YAP and inhibited TEAD1 expression. Inhibition of Lats1 accelerated HG-induced proliferation and expression of fibronectin and collagen IV. Verteporfin, an inhibitor of YAP, suppressed HG-induced proliferation and expression of fibronectin and collagen IV. However, Sesn2 overexpression reversed Lats1 deficiency-induced Lats1 and YAP phosphorylation, nuclear expression levels of YAP and TEAD1, and proliferation and fibronectin and collagen IV expressions in HMCs exposed to HG. In addition, antioxidant NAC or tempol treatment promoted phosphorylation of Lats1 and YAP and inhibited TEAD1 expression, proliferation, and fibronectin and collagen IV accumulation in HG-treated HMCs. Taken together, Sesn2 overexpression inhibited mesangial cell proliferation and fibrosis via regulating Hippo pathway in diabetic nephropathy. Induction of Sesn2 may be a potential therapeutic target in diabetic nephropathy.

Effect of Ibrutinib on the IFN Response of Chronic Lymphocytic Leukemia Cells.

The Bruton's tyrosine kinase (BTK) inhibitor ibrutinib has profound activity in chronic lymphocytic leukemia (CLL) but limited curative potential by itself. Residual signaling pathways that maintain survival of CLL cells might be targeted to improve ibrutinib's therapeutic activity, but the nature of these pathways is unclear. Ongoing activation of IFN receptors in patients on ibrutinib was suggested by the presence of type I and II IFN in blood together with the cycling behavior of IFN-stimulated gene (ISG) products when IFN signaling was blocked intermittently with the JAK inhibitor ruxolitinib. IFN signaling in CLL cells from human patients was not prevented by ibrutinib in vitro or in vivo, but ISG expression was significantly attenuated in vitro. ISGs such as CXCL10 that require concomitant activation of NF-κB were decreased when this pathway was inhibited by ibrutinib. Other ISGs, exemplified by LAG3, were decreased as a result of inhibited protein translation. Effects of IFN on survival remained intact as type I and II IFN-protected CLL cells from ibrutinib in vitro, which could be prevented by ruxolitinib and IFNR blocking Abs. These observations suggest that IFNs may help CLL cells persist and specific targeting of IFN signaling might deepen clinical responses of patients on ibrutinib.

Development of the Blood-Brain Barrier in Ducks.

The blood-brain barrier (BBB) is an important internal barrier. Herein, the electron microscope examination of duck BBB was performed during the brain development. Meanwhile, the genes/proteins of tight junctions (TJs) including zonula occludens-1, occludin, and claudin-5 in the duck brain were detected by Q-PCR and immunohistochemistry. The results showed the density of capillaries in the brain gradually increased during the embryonic period. The generation of the BBB and the specialization of its components occurred mainly in the embryonic stage. During this period, the endothelial cells (ECs) became thinner and pinocytic vesicles decreased; the TJs between EC membranes became longer and more electron-dense; the basement membrane surrounding ECs and pericytes gradually thickened; and the astrocyte foot processes appeared to wrap around the vessels. By the day of hatching (P1), the whole set of duck BBB structures was completely assembled and gradually improved in the subsequent growth process. Interestingly, compared with the cerebrum and cerebellum, the maturity level of the midbrain BBB was earlier seen during the embryonic stage. The expression of TJs increased during the embryonic period and remained stable by post-hatching. The study systematically investigated the histochemical and ultrastructural features of duck BBB during development and explored the corresponding relationship between structure and function.

Transformation of Mitochondrial Architecture and Dynamics in the Chinese Soft-Shelled Turtle (Pelodiscus sinensis) During Hibernation.

Hibernation is a biological status during which hibernating animals acclimatize themselves to reduced energy consumption through extreme but governed decline in self-metabolism. The role of mitochondria (Mt) in metabolic suppression during hibernation has already been elaborated in different organs and species. Nonetheless, the concretely changing process of mitochondrial architecture and the mechanism underlying this transformation during hibernation remains unclear. Herein, the present study was aimed at clarifying the detailed alteration of mitochondrial morphology and its potential role in the Chinese soft-shelled turtle (Pelodiscus sinensis) during different stages of hibernation. Compared with the nonhibernation period, the mitochondrial architecture was changing from round to crescent, and lipid droplet (LD)/Mt interaction was enhanced during hibernation, as observed by transmission electron microscopy (TEM). Further ultrastructural analysis uncovered that mitochondrial fusion was promptly accelerated in the early stage of hibernation, followed by mitochondrial fission in the middle stage, and mitophagy was boosted in the late stage. Moreover, gene and protein expression related to mitochondrial fusion, fission, and mitophagy accorded closely with the mitochondrial ultrastructural changes in different stages of hibernation. Taken together, our results clarified that the transformation of mitochondrial architecture and mitochondrial dynamics are of vital importance in maintaining internal environment homeostasis of Pelodiscus sinensis.

Carbohydrate response element-binding protein regulates lipid metabolism via mTOR complex1 in diabetic nephropathy.

Lipid deposition caused by the disorder of renal lipid metabolism is involved in diabetic nephropathy (DN). Carbohydrate response element-binding protein (ChREBP) is a key transcription factor in high glucose-induced cellular fat synthesis. At present, the regulation and mechanism of ChREBP on fat metabolism in diabetic kidneys are still unclear. In this study, we showed that lack of ChREBP significantly improved renal injury, inhibited oxidative stress, lipid deposition, fatty acid synthase (FASN), acetyl-CoA carboxylase (ACC) and thioredoxin-interacting protein (TXNIP) expression, as well as the activity of mammalian target of rapamycin complex 1 (mTORC1) in diabetic kidneys. Meanwhile, ChREBP deficiency upregulated the expression of peroxisome proliferator-activated receptor-α (PPARα), carnitine palmitoyltransferaser 1A (CPT1A) and acyl-coenzyme A oxidase 1 (ACOX1) in diabetic kidneys. In vitro, knockdown of ChREBP attenuated lipid deposition, mTORC1 activation, and expression of FASN and ACC, increased PPARα, CPT1A, and ACOX1 expression in HK-2 cells and podocytes under high glucose (HG) conditions. Moreover, HG-induced lipid deposition, increased expression of FASN and ACC and decreased expression of PPARα, CPT1A, and ACOX1 were reversed by rapamycin, a specific inhibitor of mTORC1, in HK-2 cells. These results indicate that ChREBP deficiency alleviates diabetes-associated renal lipid accumulation by inhibiting mTORC1 activity and suggest that reduction of ChREBP is a potential therapeutic strategy to treat DN.

Photofluorochromic water-dispersible nanoparticles for single-photon-absorption upconversion cell imaging.

Photofluorochromic diarylethene (DAE) molecules have been widely investigated due to their excellent fatigue resistance and thermal stability. However, the poor water solubility of DAEs limits their biological applications to some extent. Herein, we reported two kinds of water-dispersible DAE nanoparticles (DAEI-NPs and DAEB-NPs), in which DAE molecules were stabilized by the amphiphilic polymer DSPE-mPEG2000 using the nanoprecipitation approach. The fabricated nanoparticles retain well-controlled luminescence and fluorescence photoswitching properties in aqueous solution, which could be reversibly switched on and off under the alternating irradiation of ultraviolet (UV) and visible light. In addition, the closed-ring isomers of DAEB-NPs performed hot-band-absorption-based photon upconversion when excited by a 593.5 nm laser. Bearing excellent photophysical properties and low cytotoxicity, DAEB-NPs were applicable for upconversion cell imaging without high-excitation power density and free from oxygen removal. Additionally, the imaging process could be switched on by regulating the photofluorochromic nanoparticles.