Publications by authors named "Jia Qi"

433 Publications

Hierarchical Similarity Learning for Aliasing Suppression Image Super-Resolution.

IEEE Trans Neural Netw Learn Syst 2022 Aug 5;PP. Epub 2022 Aug 5.

As a highly ill-posed issue, single-image super-resolution (SISR) has been widely investigated in recent years. The main task of SISR is to recover the information loss caused by the degradation procedure. According to the Nyquist sampling theory, the degradation leads to the aliasing effect and makes it hard to restore the correct textures from low-resolution (LR) images. In practice, there are correlations and self-similarities among the adjacent patches in the natural images. This article considers the self-similarity and proposes a hierarchical image super-resolution network (HSRNet) to suppress the influence of aliasing. We consider the SISR issue in the optimization perspective and propose an iterative solution pattern based on the half-quadratic splitting (HQS) method. To explore the texture with local image prior, we design a hierarchical exploration block (HEB) and progressive increase the receptive field. Furthermore, multilevel spatial attention (MSA) is devised to obtain the relations of adjacent feature and enhance the high-frequency information, which acts as a crucial role for visual experience. The experimental result shows that HSRNet achieves better quantitative and visual performance than other works and remits the aliasing more effectively.
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http://dx.doi.org/10.1109/TNNLS.2022.3191674DOI Listing
August 2022

Tongluo Yishen Decoction Ameliorates Renal Fibrosis NLRP3-Mediated Pyroptosis and .

Front Pharmacol 2022 6;13:936853. Epub 2022 Jul 6.

Department of Nephropathy, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China.

In this study, we investigated the mechanism of Tongluo Yishen (TLYS) decoction in more detail, from the perspective of pyroptosis in the unilateral ureteral ligation (UUO) model and the hypoxia-induced renal tubular epithelial (NRK-52E) cell. The UUO model was used, and after 14 days of TLYS intervention, rats were tested for blood creatinine and urea nitrogen, HE staining was used to observe the pathological changes in the kidney, Masson staining was used to assess the degree of interstitial fibrosis, western blot was used to detect the changes of α-smooth muscle actin (α-SMA) protein expression level, immunohistochemistry and western blot detected the changes in protein expression levels of NOD-like receptor protein 3 inflammasome (NLRP3), gasdermin D (GSDMD), cysteinyl aspartate specific proteinase (caspase-1), interleukin 18 (IL-18) and interleukin 1β (I L-1β). A hypoxia model was created using NRK-52E cell, and after different concentrations of TLYS decoction intervention, the changes in the expression levels of pyroptosis were used with immunofluorescence and western blot methods. TLYS decoction improved renal function, delayed the advancement of renal interstitial fibrosis, and inhibited pyroptosis in UUO rats. Furthermore, we observed that TLYS can mitigate hypoxia-induced NRK-52E cell damage via the suppression of the NLRP3-mediated pyroptosis. TLYS decoction exert renoprotective effects by inhibiting NLRP3-mediated pyroptosis.
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http://dx.doi.org/10.3389/fphar.2022.936853DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9298980PMC
July 2022

A large geographic-scale characterization of organochlorine pesticides (OCPs) in surface sediments and multiple aquatic foods of inland freshwater aquaculture ponds in China: Co-occurrence, source and risk assessment.

Environ Pollut 2022 Sep 6;308:119716. Epub 2022 Jul 6.

Institute of Quality Standards and Testing Technology for Agro-Products, Chinese Academy of Agricultural Sciences, Key Laboratory of Agri-food Quality and Safety, Ministry of Agriculture and Rural Affairs, Chinese Academy of Agricultural Sciences, Beijing, 100081, China. Electronic address:

Inland freshwater aquaculture ponds (IFAPs) represent the key component of the global lentic freshwater environment and are increasingly important for global aquaculture production, yet the occurrence of organochlorine pesticides (OCPs) in these pond systems remains largely unknown. Here, we characterized the residual concentrations of 19 individual OCPs in sediments and in cultured fish and crustacean species (crabs, shrimp, crayfish and lobster), which were on-spot sampled from the IFAPs at a large region-scale in China. The total OCP levels in sediments varied dramatically between regions. Crabs presented the greatest OCP contamination among the studied species. Dichlorodiphenyltrichloroethanes (DDTs) was the dominating contaminant in sediments and crabs and its stable degradation products 4,4'-DDE and 4,4'-DDD were co-occurrent between these two compartments. The diagnostic ratio analysis indicated fresh inputs of DDTs, lindane and aldrin in multiple regions, which may be resulted from agricultural soil erosion, surface runoff and local anthropogenic activities. Ecological impacts of these pesticides could be expected at some sites due to their levels in sediments above the risk level. Risk assessment based on the OCP levels corrected by the cooking loss revealed that daily consumption of the IFAPs-derived aquatic foods may pose carcinogenic risks in humans.
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http://dx.doi.org/10.1016/j.envpol.2022.119716DOI Listing
September 2022

Cross-Disciplinary Application for Qualitative Magnesium Corrosion Assays.

Bioinorg Chem Appl 2022 28;2022:8289447. Epub 2022 Jun 28.

The Conversationalist Club, School of Stomatology, Shandong First Medical University and Shandong Academy of Medical Sciences, Tai'an, Shandong 271016, China.

At the moment, unserviceable magnesium implants make a good case in point for further responsible study in this field. Whether we are willing to admit it or not, existing methods for corrosion monitoring are exposed to susceptibility and instability. Interdisciplinary theories and the existing corrosion experiments were combined based on their various merits for developing an accurate and precise corroding experiment for Mg/Mg alloys. We used the water-soluble tetrazolium-8 (WST-8) reagent to further complete the immersion experiment. The color change of the solution reflects the rationale of corrosion, followed by monitoring the degree of corrosion. The feasibility of this idea will be demonstrated.
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http://dx.doi.org/10.1155/2022/8289447DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9256404PMC
June 2022

Different cellular mechanism of imidacloprid and acetamiprid by a combined targeted lipidomics and metabolomics approach in Neuro-2a cells.

Toxicol In Vitro 2022 Sep 30;83:105426. Epub 2022 Jun 30.

Institute of Quality Standards and Testing Technology for Agro-Products, Chinese Academy of Agricultural Sciences, Key Laboratory of Agri-food Quality and Safety, Ministry of Agriculture and Rural Affairs, Beijing 100081, China. Electronic address:

As commonly used neonicotinoid insecticides for pest control, imidacloprid (IMI) and acetamiprid (ACE) posed neurotoxicity effects on living organisms. However, researches of the differences in toxicity mechanism between these two neonicotinoid insecticides are still limited. In this study, different cellular metabolism perturbations and redox homeostasis damages induced by IMI and ACE exposure in Neuro-2a cells were investigated. Distinct elevation of lactate dehydrogenase (LDH) activity and caspase 7 level demonstrated the influences on necrosis and apoptosis. There were 21 and 12 metabolites screened out as potential biomarkers after IMI and ACE exposure, including lipids and amino acids. Remarkable decrease of lipid hydroperoxides (LOOH) and increase of reactive oxygen species (ROS) generation were found only in the ACE20 group. Interference with glutathione metabolism pathway was further validated by detecting GPx (glutathion peroxidase), GSH (reduced glutathione) and GSSG (oxidized glutathione) levels. Taken together, the metabolic interferences and oxidative damages in ACE20 group were significantly different from the other three exposure groups. These results help to explore the toxicity mechanism of neonicotinoid insecticides from multiple perspectives. This study provides scientific basis for evaluating toxicity of different neonicotinoid insecticides.
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http://dx.doi.org/10.1016/j.tiv.2022.105426DOI Listing
September 2022

Sperm-borne proteins improve rabbit cloning efficiency via regulating embryonic cleavage and epigenetics.

Proteomics 2022 Jul 2:e2200020. Epub 2022 Jul 2.

Laboratory Animal Center, Xi'an Jiaotong University Health Science Centre, Xi'an, Shaanxi, China.

Somatic cell nuclear transfer (SCNT) shows great application value in the generation of transgenic animals, protection of endangered species, and therapeutic cloning. However, the cloning efficiency is still very low, which greatly restricts its application. Compared to fertilized embryos, cloned embryos lack the sperm proteins, which are considered to play an important role in embryonic development. Here, we compared the sperm proteome, with that of donor fibroblasts and oocytes, and identified 342 proteins unique to sperm, with 42 being highly expressed. The 384 proteins were mainly enriched in the categories of post-translational modification and cytoskeletal arrangement. Extracts of soluble sperm or fibroblast proteins were injected into cloned embryos, and the result showed that injection of sperm protein significantly inhibited abnormal embryonic cleavage, significantly decreased the level of trimethylated histone H3 Lys9 (H3K9me3) and the apoptotic index, and increased the inner cell mass (ICM)-to-trophectoderm (TE) ratio. More importantly, the sperm proteins also significantly enhanced the birthrate. The results of in vitro and in vivo experiments demonstrate that sperm-derived proteins improve embryo cloning efficiency. Our findings not only provide new insights into ways to overcome low cloning efficiency, but also add to the understanding of sperm protein function.
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http://dx.doi.org/10.1002/pmic.202200020DOI Listing
July 2022

Identification of flexible Pif1-DNA interactions and their impacts on enzymatic activities.

Nucleic Acids Res 2022 Jun 24. Epub 2022 Jun 24.

Beijing National Laboratory for Condensed Matter Physics, Institute of Physics, Chinese Academy of Sciences, Beijing 100190, China.

Flexible regions in biomolecular complexes, although crucial to understanding structure-function relationships, are often unclear in high-resolution crystal structures. In this study, we showed that single-molecule techniques, in combination with computational modeling, can characterize dynamic conformations not resolved by high-resolution structure determination methods. Taking two Pif1 helicases (ScPif1 and BsPif1) as model systems, we found that, besides a few tightly bound nucleotides, adjacent solvent-exposed nucleotides interact dynamically with the helicase surfaces. The whole nucleotide segment possessed curved conformations and covered the two RecA-like domains of the helicases, which are essential for the inch-worm mechanism. The synergetic approach reveals that the interactions between the exposed nucleotides and the helicases could be reduced by large stretching forces or electrostatically shielded with high-concentration salt, subsequently resulting in reduced translocation rates of the helicases. The dynamic interactions between the exposed nucleotides and the helicases underlay the force- and salt-dependences of their enzymatic activities. The present single-molecule based approach complements high-resolution structural methods in deciphering the molecular mechanisms of the helicases.
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http://dx.doi.org/10.1093/nar/gkac529DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9262596PMC
June 2022

Synthesis and in Vivo Evaluation of Triphenylphosphonium Conjugated Trimetazidine with Enhanced Cardioprotection and Ability to Restore Mitochondrial Function.

Chem Biodivers 2022 Jun 17:e202200445. Epub 2022 Jun 17.

School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou, 510006, P. R. China.

Trimetazidine exhibits great therapeutic potential in cardiovascular diseases and mitochondria-mediated cardioprotection by trimetazidine has been widely reported. In this study, to enhance its cardioprotection, the triphenylphosphonium-based modification of trimetazidine was conducted to deliver it specifically to mitochondria. Fifteen triphenylphosphonium (TPP) conjugated trimetazidine analogs were designed and synthesized. Their protective effects were evaluated in vivo using a tert-butyl hydroperoxide (t-BHP) induced zebrafish injury model. Structure-activity relationship correlations revealed the best way to couple the TPP moiety to trimetazidine, and led to a new conjugate (18a) with enhanced therapeutic properties. Compared to trimetazidine, 18a effectively protects against heart injury in the zebrafish model at a much lower concentration. Further study in t-BHP treated zebrafish and H9c2 cells demonstrated that 18a protects against cardiomyocyte death and damage by inhibiting excessive production of ROS, maintaining mitochondrial morphology, and preventing mitochondrial dysfunction. Consequently, 18a can be regarded as a potential therapeutic agent for cardioprotection.
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http://dx.doi.org/10.1002/cbdv.202200445DOI Listing
June 2022

Postoperative hypothalamic damage predicts postoperative weight gain in patients with adult-onset craniopharyngioma.

Obesity (Silver Spring) 2022 07 16;30(7):1357-1369. Epub 2022 Jun 16.

Department of Neurosurgery, The First Affiliated Hospital of Nanchang University, Nanchang, China.

Objective: This study aimed to recapitulate the change trajectory of postoperative weight and investigate the association between postoperative hypothalamic damage and weight gain and hypothalamic obesity (HO) in patients with adult-onset craniopharyngioma.

Methods: The data of 96 patients with surgically treated primary adult-onset craniopharyngioma were retrospectively analyzed. The association between postoperative hypothalamic damage based on magnetic resonance images or endoscopic observation and postoperative weight gain and HO was determined by multivariable logistic regression.

Results: Forty-seven (49.0%) patients and 18 (18.8%) patients experienced clinically meaningful weight gain (≥5%) and HO at last follow-up, respectively. Postoperative weight significantly increased during the first 6 months following surgery, followed by stabilization. Both grade 2 postoperative hypothalamus damage, as evaluated by the magnetic resonance imaging classification system of Müller et al., and higher scores based on the Roth et al. hypothalamic lesion score were significantly associated with postoperative weight gain of ≥5% (p = 0.005 and p = 0.002) and with HO (p = 0.001 and p = 0.008). Additionally, bilateral hypothalamic injury as evaluated by the Hong et al. hypothalamic injury pattern based on endoscopic observation (p = 0.008) could predict postoperative weight gain ≥5%.

Conclusions: Significant postoperative weight gain is common in patients with adult-onset craniopharyngioma. Postoperative hypothalamic damage can predict clinically meaningful weight gain and HO.
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http://dx.doi.org/10.1002/oby.23447DOI Listing
July 2022

Novel GSK-3 kinase inhibitor Pym-5 induces GSK-3β rather than GSK-3α-dependent melanogenesis in murine melanoma cells.

J Dermatol Sci 2022 Jun 11;106(3):170-180. Epub 2022 May 11.

Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China. Electronic address:

Background: Glycogen synthase kinase-3 (GSK-3) inhibitors are considered to activate Wnt/β-Catenin, which remains a controversial topic in melanoma treatment.

Objective: Here, we have developed Pym-5, an attractive GSK-3 inhibitor. Using Pym-5 as a chemical tool to probe the GSK-3 biology, we aimed to investigate the potential of GSK-3 inhibition as a strategy of melanoma treatment and underlying mechanisms.

Methods: Using pigment B16 and B16BL6 murine melanoma model in vitro and a zebrafish pigmentation model in vivo, we investigated Pym-5-meditaed activation of Wnt/β-Catenin, melanogenesis and antitumor response in melanoma treatment.

Results: We found that Pym-5 delayed the growth and promoted melanogenesis of melanoma cells. Pym-5 activated the transcription of β-Catenin and responsive targets genes (AXIN2 and MITF), melanin biosynthesis genes (TYR, TYRP1 and TYRP2) and eventually elevated the production of melanin. Interestingly, genetic inactivation of GSK-3β, but not its paralogue GSK-3α, compromised Pym-5-mediated melanogenesis in B16 and B16BL6 cells.

Conclusion: These data provide insight into the potential therapeutic benefits obtained from activation of Wnt/β-Catenin signaling pathway and how Pym-5 can regulate melanin production and the rationale for future clinical application of GSK-3 inhibitor in melanoma patients.
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http://dx.doi.org/10.1016/j.jdermsci.2022.05.003DOI Listing
June 2022

Loss of Renewal of Extracellular Vesicles: Harmful Effects on Embryo Development in vitro.

Int J Nanomedicine 2022 19;17:2301-2318. Epub 2022 May 19.

Laboratory Animal Center, Xi'an Jiaotong University Health Science Centre, Xi'an, Shaanxi, People's Republic of China.

Background: Extracellular vesicles (EVs), as a promising platform for drug delivery, have attracted much attention. Degradation and regeneration of EVs maintain their homeostasis in vivo, but this regeneration is missing in the in vitro culture (IVC) system, which is likely to lead to negative effects. It is particularly concerning that most studies involving the addition of EVs in IVC seem to overlook this point.

Methods: We used rabbit embryos and oviduct fluid EVs as a model of embryo development to examine the effect of loss or gain of EV functionality in an IVC system. Embryonic development ratios were determined in each group. Malondialdehyde and ammonium ions in the culture medium were measured. RNA-seq, reactive oxygen species (ROS) staining, immunofluorescence of LC3 and H3K36me3, and qPCR of oxidative stress-related genes and autophagy-related genes of blastocysts in the in vivo group, non-EVs group, con-EVs group, and R-EVsM group was implemented.

Results: Incubation of embryos with 9.1×10 EV particles/mL had a positive effect at 48 h and 72 h, which disappeared by 96 h, however. EVs at a concentration of 9.1×10 particles/mL even showed a negative effect at 96 h. As culture time in the IVC system was increased, the amount of malondialdehyde and ammonium ions in the culture medium was increased, and there was a decrease in embryonic development activity of EVs. Lack of EV renewal in the IVC system impaired embryonic development competence, while replacement of EVs and medium during IVC could sustain embryonic development. Loss or gain of renewal in the IVC system affected EVs' influence on embryo transcriptome, embryonic ROS, autophagy, epigenetic state and apoptosis.

Conclusion: Loss of renewal in the IVC system affected EVs' role in embryonic development by causing an imbalance in ROS, autophagy, abnormal H3K36me3 levels and apoptosis, while gain of renewal in the IVC system reduced these adverse effects and ensured the beneficial function of EVs.
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http://dx.doi.org/10.2147/IJN.S354003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9126234PMC
May 2022

Bent, But Not Broken: Locus-of-Hope and Well-Being Among Malaysians Facing Economic Challenges Amidst the COVID-19 Pandemic.

Psychol Stud (Mysore) 2022 May 17:1-13. Epub 2022 May 17.

Department of Psychology, Faculty of Behavioural Sciences, Languages, and Education, HELP University, Kuala Lumpur, Malaysia.

Hope is conceptualized as a cognitive set that has often been studied in the context of adversity. No studies, however, directly examine how locus-of-hope (LOH) influences psychological outcomes among vulnerable populations within collectivist cultural contexts. We address this gap by assessing the relationships between LOH and well-being among Malaysians facing financial struggles during the COVID-19 pandemic. We hypothesized that LOH will predict well-being but that external LOH will more strongly predict well-being than internal LOH. One-hundred and fifty-two (152) Malaysians (63 men, 89 women, average age 29.69 years old) who have (1) experienced loss of employment status (2) decrease in salary earnings or (3) earn below the lower 40% threshold of national household incomes completed a series of questionnaires assessing their LOH and well-being. Results indicate that controlling for age, perceptions of government efforts and trait optimism, LOH significantly predict well-being. Findings also show that internal LOH and LOH-family were the strongest predictors of well-being. Theoretical and practical implications are discussed in light of these findings.
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http://dx.doi.org/10.1007/s12646-022-00653-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9110276PMC
May 2022

Follicular free fatty acid metabolic signatures and their effects on oocyte competence in non-obese PCOS patients.

Reproduction 2022 05 23;164(1):1-8. Epub 2022 May 23.

Department of Endocrinology and Metabolism, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

In Brief: Polycystic ovary syndrome (PCOS) is a common cause of anovulatory infertility in women. This study identified changes in free fatty acids profiles in the follicular fluid that may lead to better diagnosis and management of infertility in PCOS women.

Abstract: Polycystic ovary syndrome (PCOS) is a heterogeneous disease characterized by various endocrine/metabolic disorders and impaired reproductive potential. Alterations in oocyte competence are considered potentially causative factors for infertility in PCOS women and analyzing the composition of follicular fluid in these patients may help to identify which changes have the potential to alter oocyte quality. In this study, free fatty acid metabolic signatures in follicular fluid were performed to identify changes that may impact oocyte competence in non-obese PCOS women. Sixty-four non-obese women (32 with PCOS and 32 age- and BMI-matched controls) undergoing in vitro fertilization were recruited. Embryo quality was morphologically assessed. Free fatty acid metabolic profiling in follicular fluid was performed using gas/liquid chromatography-mass spectrometry. Principal component analysis and orthogonal partial least squares-discriminant analysis models were further constructed. Nine free fatty acids and 24 eicosanoids were identified and several eicosanoids synthesized by the cyclooxygenase pathway were significantly elevated in PCOS patients compared to controls. The combination of PGE2, PGF2α, PGJ2, and TXB2 had an area under the curve of 0.867 (0.775-0.960) for PCOS discrimination. Furthermore, follicular fluid levels of PGE2 and PGJ2 were negatively correlated with high-quality embryo rate in PCOS patients (P < 0.05). Metabolomic analysis revealed that follicular fluid lipidomic profiles undergo changes in non-obese PCOS women, which suggests that identifying changes in important metabolic signatures may give us a better understanding of the pathogenesis of PCOS. Furthermore, elevated PGE2 and PGJ2 concentrations may contribute to impaired oocyte competence in non-obese PCOS patients.
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http://dx.doi.org/10.1530/REP-22-0023DOI Listing
May 2022

Transcription Factor ASCL1 Acts as a Novel Potential Therapeutic Target for the Treatment of the Cushing's Disease.

J Clin Endocrinol Metab 2022 07;107(8):2296-2306

Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China.

Background: The pathogenesis of Cushing's disease (CD) is still not adequately understood despite the identification of somatic driver mutations in USP8, BRAF, and USP48. In this multiomics study, we combined RNA sequencing (RNA-seq) with Sanger sequencing to depict transcriptional dysregulation under different gene mutation backgrounds. Furthermore, we evaluated the potential of achaete-scute complex homolog 1 (ASCL1), a pioneer transcription factor, as a novel therapeutic target for treatment of CD and its possible downstream pathway.

Methods: RNA-seq was adopted to investigate the gene expression profile of CD, and Sanger sequencing was adopted to detect gene mutations. Bioinformatics analysis was used to depict transcriptional dysregulation under different gene mutation backgrounds. The function of ASCL1 in hormone secretion, cell proliferation, and apoptosis were studied in vitro. The effectiveness of an ASCL1 inhibitor was evaluated in primary CD cells, and the clinical relevance of ASCL1 was examined in 68 patients with CD. RNA-seq in AtT-20 cells on Ascl1 knockdown combined with published chromatin immunoprecipitation sequencing data and dual luciferase assays were used to explore downstream pathways.

Results: ASCL1 was exclusively overexpressed in USP8-mutant and wild-type tumors. Ascl1 promoted adrenocorticotrophin hormone overproduction and tumorigenesis and directly regulated Pomc in AtT-20 cells. An ASCL1 inhibitor presented promising efficacy in both AtT-20 and primary CD cells. ASCL1 overexpression was associated with a larger tumor volume and higher adrenocorticotrophin secretion in patients with CD.

Conclusion: Our findings help to clarify the pathogenesis of CD and suggest that ASCL1 is a potential therapeutic target the treatment of CD.

Summary: The pathogenesis of Cushing's disease (CD) is still not adequately understood despite the identification of somatic driver mutations in USP8, BRAF, and USP48. Moreover, few effective medical therapies are currently available for the treatment of CD. Here, using a multiomics approach, we first report the aberrant overexpression of the transcription factor gene ASCL1 in USP8-mutant and wild-type tumors of CD. Ascl1 promoted adrenocorticotrophin hormone overproduction and tumorigenesis and directly regulated Pomc in mouse AtT-20 cells. Notably, an ASCL1 inhibitor presented promising efficacy in both AtT-20 and primary CD cells. Importantly, ASCL1 overexpression was associated with a larger tumor volume and higher adrenocorticotrophin secretion in patients with CD. Thus, our findings improve understanding of CD pathogenesis and suggest that ASCL1 is a potential therapeutic target the treatment of CD.
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http://dx.doi.org/10.1210/clinem/dgac280DOI Listing
July 2022

-GlcNAc modification mediates aquaporin 3 to coordinate endometrial cell glycolysis and affects embryo implantation.

J Adv Res 2022 03 30;37:119-131. Epub 2021 Jun 30.

Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, Liaoning, China.

Introduction: -linked β-D-N-acetylglucosamine (-GlcNAc) modification is a post-translational modification in which a single -GlcNAc is added to serine or threonine residues in nuclear, cytoplasmic, and mitochondrial proteins, and is involved in a variety of physiological processes.

Objectives: In the present study, the role of -GlcNAcylation in embryo implantation was evaluated. Furthermore, whether -GlcNAcylation is involved in orchestrating glucose metabolism to influence endometrial cell physiological functions was investigated.

Methods: Different endometrial tissues were detected using immunohistochemistry. Pregnant mouse models were established to verify molecular expression. -GlcNAc transferase and aquaporin 3 (AQP3) knockdown were used to detect embryo implantation efficiency and . Western blotting and immunofluorescence were used to detect protein expression and stability. Dual luciferase reporter assay and chromatin immunoprecipitation (ChIP) were used to verify the binding transcription factor. Glycolysis was detected using bioenergy analyzer, and metabolites were analyzed using isotope 13C-labeled LC-MS. Metabolic-related genes were determined using RNA sequencing.

Results: Activation of endometrial hexosamine biosynthetic pathway (HBP) caused elevated -GlcNAcylation during the window of implantation, affecting endometrial cell function and embryo implantation. Specifically, elevated -GlcNAcylation increased glucose uptake glucose transporter 1 (GLUT1) leading to glucose metabolic flow into the pentose phosphate pathways and HBP, which regulate the metabolic reprogramming of endometrial cells. Furthermore, -GlcNAcylation mediated the intracellular transport of glycerol to support and compensate for glycolysis through regulation of AQP3. Unexpectedly, elevated AQP3 also increased glucose uptake GLUT1. These processes maintained higher metabolic requirements for endometrial physiology. Furthermore, the transcription factor SP1 specifically bound to the AQP3 promoter region, and -GlcNAcylation of SP1 increased its stability and transcriptional regulation of AQP3 which is associated with -GlcNAcylation of SP1.

Conclusion: Overall, -GlcNAcylation regulated glucose metabolism in endometrial cells, and AQP3-mediated compensation provides new insights into the communication between glycolysis and -GlcNAcylation.
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http://dx.doi.org/10.1016/j.jare.2021.06.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9039670PMC
March 2022

Gandi Capsule Improved Podocyte Lipid Metabolism of Diabetic Nephropathy Mice through SIRT1/AMPK/HNF4A Pathway.

Oxid Med Cell Longev 2022 18;2022:6275505. Epub 2022 Apr 18.

Department of Clinical Pharmacy, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.

Podocyte lipid accumulation is a potential therapeutic target for diabetic nephropathy (DN). This study was aimed at clarifying the mechanism of Gandi capsule (GDC) ameliorating DN by regulating the lipid metabolism of podocytes. Network pharmacology methods were performed to screen the key molecules and potential targets of GDC for constructing the molecular-protein interaction network of GDC and conducting signal pathway enrichment analysis. GDC was predicted to ameliorate DN through SIRT1/AMPK/HNF4A pathway. Our results showed that GDC improved renal function in db/db mice. Besides, GDC exhibited effectiveness in relieving kidney tissue damage and renal lipid accumulation in db/db mice, and same effects were present in GDC-active ingredient baicalin. We further proved the new role of HNF4A in the lipid metabolism of DN mediated by SIRT1 and AMPK signaling pathways. The results suggested decreased expression of SIRT1 and p-AMPK in the kidney tissue and increased expression of HNF4A of db/db mice compared with the control group. GDC and baicalin could reverse these expression changes. Furthermore, similar expression changes were observed in the murine podocyte cell line (MPC-5) treated with different concentrations of GDC and baicalin. Our research suggested that GDC and its active ingredient baicalin could alleviate the abnormal lipid metabolism in the kidney of db/db mice and might exert renal protection through the SIRT1/AMPK/HNF4A pathway.
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http://dx.doi.org/10.1155/2022/6275505DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9038418PMC
April 2022

Three-Dimensional Large-Scale Fused Silica Microfluidic Chips Enabled by Hybrid Laser Microfabrication for Continuous-Flow UV Photochemical Synthesis.

Micromachines (Basel) 2022 Mar 30;13(4). Epub 2022 Mar 30.

Engineering Research Center for Nanophotonics and Advanced Instrument, School of Physics and Electronic Science, East China Normal University, Shanghai 200241, China.

We demonstrate a hybrid laser microfabrication approach, which combines the technical merits of ultrafast laser-assisted chemical etching and carbon dioxide laser-induced in situ melting for centimeter-scale and bonding-free fabrication of 3D complex hollow microstructures in fused silica glass. With the developed approach, large-scale fused silica microfluidic chips with integrated 3D cascaded micromixing units can be reliably manufactured. High-performance on-chip mixing and continuous-flow photochemical synthesis under UV irradiation at ~280 nm were demonstrated using the manufactured chip, indicating a powerful capability for versatile fabrication of highly transparent all-glass microfluidic reactors for on-chip photochemical synthesis.
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http://dx.doi.org/10.3390/mi13040543DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9026117PMC
March 2022

Ultralight Magnetic and Dielectric Aerogels Achieved by Metal-Organic Framework Initiated Gelation of Graphene Oxide for Enhanced Microwave Absorption.

Nanomicro Lett 2022 Apr 19;14(1):107. Epub 2022 Apr 19.

Institute of Advanced Materials and Flexible Electronics (IAMFE), School of Chemistry and Materials Science, Nanjing University of Information Science and Technology, Nanjing, 210044, People's Republic of China.

Highlights: Metal-organic frameworks (MOFs) are used to directly initiate the gelation of graphene oxide (GO), producing MOF/rGO aerogels. The ultralight magnetic and dielectric aerogels show remarkable microwave absorption performance with ultralow filling contents. The development of a convenient methodology for synthesizing the hierarchically porous aerogels comprising metal-organic frameworks (MOFs) and graphene oxide (GO) building blocks that exhibit an ultralow density and uniformly distributed MOFs on GO sheets is important for various applications. Herein, we report a facile route for synthesizing MOF/reduced GO (rGO) aerogels based on the gelation of GO, which is directly initiated using MOF crystals. Free metal ions exposed on the surface of MIL-88A nanorods act as linkers that bind GO nanosheets to a three-dimensional porous network via metal-oxygen covalent or electrostatic interactions. The MOF/rGO-derived magnetic and dielectric aerogels [email protected]/rGO and Ni-doped [email protected]/rGO show notable microwave absorption (MA) performance, simultaneously achieving strong absorption and broad bandwidth at low thickness of 2.5 (- 58.1 dB and 6.48 GHz) and 2.8 mm (- 46.2 dB and 7.92 GHz) with ultralow filling contents of 0.7 and 0.6 wt%, respectively. The microwave attenuation ability of the prepared aerogels is further confirmed via a radar cross-sectional simulation, which is attributed to the synergistic effects of their hierarchically porous structures and heterointerface engineering. This work provides an effective pathway for fabricating hierarchically porous MOF/rGO hybrid aerogels and offers magnetic and dielectric aerogels for ultralight MA.
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http://dx.doi.org/10.1007/s40820-022-00851-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9019009PMC
April 2022

Anti-hypertensive medications and risk of colorectal cancer: a systematic review and meta-analysis.

Cancer Causes Control 2022 Jun 21;33(6):801-812. Epub 2022 Mar 21.

School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada.

Purpose: Antihypertensive medications may impact colorectal cancer risk. We conducted a systematic review and meta-analysis of associations, with colorectal cancer risk, of five classes of antihypertensive medications: angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), beta-blockers (BBs), calcium channel blockers (CCBs), and diuretics.

Methods: A systematic search was conducted in MEDLINE, Embase, Web of Science, and the Cochrane library to identify relevant studies evaluating associations of ACEIs, ARBs, BBs, CCBs, and diuretics with colorectal cancer risk. Meta-analytic risk ratios (RRs) and corresponding 95% confidence intervals (95% CIs) were calculated using the inverse variance method.

Results: No overall significant associations with colorectal cancer risk were observed; ACEIs (5 studies) RR 1.05, 95% CI 0.91-1.23, ARBs (5 studies) RR 0.94, 95% CI 0.80-1.11, BBs (4 studies) RR 1.00, 95% CI 0.92-1.08, CCBs (4 studies) RR 1.02, 95% CI 0.88-1.18, and diuretics (6 studies) RR 1.02, 95% CI 0.90-1.17. There was considerable heterogeneity across studies, partly explained by differences in study design and location. When stratified by study location, there was significantly reduced colorectal cancer risk for ARB use in Asian populations (2 studies, RR 0.69, 95% CI 0.58-0.83).

Conclusion: No significant colorectal cancer risk with ACEIs, BBs, CCBs, or diuretics was observed. ARB use may be associated with decreased risk of colorectal cancer in Asian populations, although additional studies in diverse populations are needed to confirm associations and help understand possible reasons for geographical differences.
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http://dx.doi.org/10.1007/s10552-022-01570-1DOI Listing
June 2022

Lifestyle factors and lung cancer risk among never smokers in the Canadian Partnership for Tomorrow's Health (CanPath).

Cancer Causes Control 2022 Jun 18;33(6):913-918. Epub 2022 Mar 18.

Cancer Control Research, BC Cancer, 2-107 675 W 10th Ave, Vancouver, BC, V5Z 1L3, Canada.

Background: Although smoking is the primary risk factor for lung cancer, 15-25% of lung cancers occur in never smokers. Emerging evidence suggests lifestyle factors are associated with lung cancer risk, but few studies among never smokers exist.

Methods: A case-control study of never smokers within the Canadian Partnership for Tomorrow's Health was conducted. At recruitment, participants provided data on lifestyle, health history and sociodemographic factors. Incident lung cancers were identified through linkage with administrative health records. Cases (n = 190) were matched to controls (n = 760) on age, sex, and follow-up time. Logistic regression analyses, adjusted for matching factors and annual income, were used to identify associations between lifestyle factors and lung cancer risk.

Results: Consumption of < 5 servings of fruits and vegetables/day was associated with higher risk of lung cancer (OR  1.50, 95% CI 1.03-2.17). Short or long sleep (≤ 6 or > 9 h/night) was also associated with increased risk of lung cancer (OR 1.52, 95% CI 1.01-2.29). No associations were observed for obesity measures, alcohol consumption, or physical activity.

Conclusion: Our findings provide evidence of a potential role between sleep, fruits and vegetable consumption, and lung cancer risk in a pan-Canadian, non-smoking population. However, the sample size is modest, and further investigation is needed.
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http://dx.doi.org/10.1007/s10552-022-01566-xDOI Listing
June 2022

Application of Nonsurgical Modalities in Improving Facial Aging.

Int J Dent 2022 24;2022:8332631. Epub 2022 Feb 24.

The Conversationalist Club, School of Stomatology, Shandong First Medical University and Shandong Academy of Medical Sciences, Tai'an, Shandong 271036, China.

Objective: This review aims to summarize different kinds of applications of minimally invasive surgery in improving facial aging to provide a comprehensive and accurate introduction on the issue of esthetic treatment of facial skin. . In the twentieth century, facial rejuvenation has become a new beauty trend. Facial cosmetology has entered a period of antiaging and rejuvenation therapies and microplastic surgery. The pursuit of beauty has promoted the development of minimally invasive plastic surgery. This review introduces the possible causes of facial aging and its related topics with a focus on facial injectable drugs, such as botulinum toxin, main filler materials (hyaluronic acid, calcium hydroxyapatite, poly L-lactic acid, collagen, autologous fat, and polymethyl methacrylate), and some current antiwrinkle technologies, such as thread lift and radiofrequency rhytidectomy.

Conclusions: Despite the difference in mechanisms of action, each technique can address facial aging involving the loss of collagen, displacement and enlargement of fat, and muscle relaxation. Combinations of these treatments can provide patients with reasonable, comprehensive, and personalized treatment plans.
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http://dx.doi.org/10.1155/2022/8332631DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8894069PMC
February 2022

NBI-921352, a first-in-class, Na1.6 selective, sodium channel inhibitor that prevents seizures in gain-of-function mice, and wild-type mice and rats.

Elife 2022 03 2;11. Epub 2022 Mar 2.

In Vivo Biology, Xenon Pharmaceuticals Inc, Burnaby, Canada.

NBI-921352 (formerly XEN901) is a novel sodium channel inhibitor designed to specifically target Na1.6 channels. Such a molecule provides a precision-medicine approach to target -related epilepsy syndromes (-RES), where gain-of-function (GoF) mutations lead to excess Na1.6 sodium current, or other indications where Na1.6 mediated hyper-excitability contributes to disease (Gardella and Møller, 2019; Johannesen et al., 2019; Veeramah et al., 2012). NBI-921352 is a potent inhibitor of Na1.6 (IC0.051 µM), with exquisite selectivity over other sodium channel isoforms (selectivity ratios of 756 X for Na1.1, 134 X for Na1.2, 276 X for Na1.7, and >583 Xfor Na1.3, Na1.4, and Na1.5). NBI-921352is a state-dependent inhibitor, preferentially inhibiting inactivatedchannels. The state dependence leads to potent stabilization of inactivation, inhibiting Na1.6 currents, including resurgent and persistent Na1.6 currents, while sparing the closed/rested channels. The isoform-selective profile of NBI-921352 led to a robust inhibition of action-potential firing in glutamatergic excitatory pyramidal neurons, while sparing fast-spiking inhibitory interneurons, where Na1.1 predominates. Oral administration of NBI-921352 prevented electrically induced seizures in a GoF mouse,as well as in wild-type mouse and ratseizure models. NBI-921352 was effective in preventing seizures at lower brain and plasma concentrations than commonly prescribed sodium channel inhibitor anti-seizure medicines (ASMs) carbamazepine, phenytoin, and lacosamide. NBI-921352 waswell tolerated at higher multiples of the effective plasma and brain concentrations than those ASMs. NBI-921352 is entering phase II proof-of-concept trials for the treatment of developmental epileptic encephalopathy (-DEE) and adult focal-onset seizures.
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http://dx.doi.org/10.7554/eLife.72468DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8903829PMC
March 2022

Preparation of corn starch/rock bean protein edible film loaded with d-limonene particles and their application in glutinous rice cake preservation.

Int J Biol Macromol 2022 May 26;206:313-324. Epub 2022 Feb 26.

College of Food Science, Sichuan Agricultural University, Yaan 625014, China. Electronic address:

Glycerol hydrogenated rosin (GEHR) and d-limonene were prepared for micro-particles by electrostatic spray method. When the GEHR/d-limonene ratio is 5.5:4.5 and the electrostatic spray extrusion speed is 1 mL/h, the best particle size (177.24 ± 17.09 μm) and embedding rate of d-limonene (41.74 ± 9.88%) are achieved. Then, rock bean protein (RP) was extracted from wild rock beans and combined with GEHR/d-limonene particles and corn starch (CS) to prepare a new type of edible film. The prepared film was characterized using Fourier transform infrared spectroscopy in terms of structural changes and physical, optical, mechanical, and thermal properties. The results show that the edible film with a ratio of 1:1 exhibited more optimized thermal (179.2 °C) and mechanical properties (TS 0.88 MPa, EAB 54.36%). Studies on freshly prepared glutinous rice cake as an object for preservation using edible film show that the films can prolong shelf life by ~2-4 d. Through this experiment, it can serve as a reference for the development of a new type of edible film.
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http://dx.doi.org/10.1016/j.ijbiomac.2022.02.139DOI Listing
May 2022

Ameliorates Renal Hypertensive Injury and Fibrosis Through the Regulation of SIRT1-Mediated Autophagy.

Front Pharmacol 2021 10;12:801094. Epub 2022 Feb 10.

Key Laboratory of Chinese Internal Medicine of Ministry of Education, Beijing Dongzhimen Hospital Addiliated to Beijing University of Chinese Medicine, Beijing, China.

Hypertensive renal injury is a complication of hypertension. () is a traditional Chinese medicine used to treat chronic kidney diseases especially renal fibrosis. Autophagy is described as a cell self-renewal process that requires lysosomal degradation and is utilized for the maintenance of cellular energy homeostasis. The present study explores the mechanism underlying 's renoprotection on hypertensive nephropathy (HN). First, HN rat models were established on spontaneously hypertensive rats (SHRs). The expression of fibrosis-related protein and autophagy-associated protein was detected . NRK-52E cells exposed to AngII were chosen to observe the potential health benefits of on renal damage. The level of extracellular matrix accumulation was detected using capillary electrophoresis immunoquantification and immunohistochemistry. After treatment with lysosomal inhibitors (chloroquine) or an autophagy activator (rapamycin), the expression of Beclin-1, LC3II, and SQSTM1/p62 was further investigated. The study also investigated the change in sirtuin1 (SIRT1), fork head box O3a (FOXO3a), and peroxidation (superoxide dismutase (SOD) and malondialdehyde (MDA)) expression when intervened by resveratrol. The changes in SIRT1 and FOXO3a were measured in patients and the SHRs. Here, we observed that significantly decreased damage to renal tubular epithelial cells and TGFβ1, α-smooth muscle actin (α-SMA), collagen I (Col-1), and fibronectin expression. Meanwhile, autophagy defects were observed both and . intervention significantly downregulated Beclin-1 and LC3II and decreased SQSTM1/p62, showing an inhibition of autophagic vesicles and the alleviation of autophagy stress. These functions were suppressed by rapamycin, and the results were just as effective as the resveratrol treatment. HN patients and the SHRs exhibited decreased levels of SIRT1 and FOXO3a. We also observed a positive correlation between SIRT1/FOXO3a and antifibrotic effects. Similar to the resveratrol group, the expression of SIRT1/FOXO3a and oxidative stress were elevated by . Taken together, our findings show that ameliorates tubulointerstitial fibrosis and delays HN progression. Renoprotection was likely attributable to the regulation of autophagic stress mediated by the SIRT1 pathway and achieved by regulating FOXO3a and oxidative stress.
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http://dx.doi.org/10.3389/fphar.2021.801094DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8866973PMC
February 2022

Multiclass Comparative Analysis of Veterinary Drugs, Mycotoxins, and Pesticides in Bovine Milk by Ultrahigh-Performance Liquid Chromatography-Hybrid Quadrupole-Linear Ion Trap Mass Spectrometry.

Foods 2022 Jan 25;11(3). Epub 2022 Jan 25.

Institute of Quality Standards and Testing Technology for Agro-Products, Chinese Academy of Agricultural Sciences, Beijing 100081, China.

A multiclass and multiresidue method for simultaneously screening and confirming veterinary drugs, mycotoxins, and pesticides in bovine milk was developed and validated with ultrahigh-performance liquid chromatography-hybrid quadrupole-linear ion trap mass spectrometry (UHPLC-Qtrap-MS). A total of 209 targeted contaminants were effectively extracted using an optimized QuEChERS method. Quantitative and qualitative confirmation were achieved simultaneously by multiple reaction monitoring-information-dependent acquisition-enhanced product ion (MRM-IDA-EPI) scan mode. The validation results exhibited a good sensitivity with the LOQs of 0.05-5 μg/kg, which was satisfactory for their MRLs in China or EU. The recoveries of in-house spiked samples were in the range of 51.20-129.76% with relative standard deviations (RSD) between replicates ( = 3) 0.82% and 19.76%. The test results of 140 milk samples from supermarkets and dairy farms in China showed that cloxacillin, aflatoxin M1, acetamiprid, and fipronil sulfone were found with lower concentrations. Combined with the residue results from the literature, penicillin G and cloxacillin (beta-lactams), enrofloxacin and ciprofloxacin (fluoroquinolones), and sulfamerazine (sulfonamides) were more frequently detected in different countries and need to receive more attention regarding their monitoring and control.
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http://dx.doi.org/10.3390/foods11030331DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8834082PMC
January 2022

A novel immune-related lncRNA pair signature for prognostic prediction and immune response evaluation in gastric cancer: a bioinformatics and biological validation study.

Cancer Cell Int 2022 Feb 10;22(1):69. Epub 2022 Feb 10.

Department of Gastroenterology Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310000, Zhejiang, China.

Background: Gastric cancer (GC), the most commonly diagnosed cancer worldwide with poor 5-year survival rate in advanced stages. Although immune-related and survival-related biomarkers, which typically comprise aberrantly expressed long non-coding RNAs (lncRNAs) and genes, have been identified, there are no reports of immune-related lncRNA pair (IRLP) signatures for GC.

Methods: In this study, we acquired lncRNA expression profiles from The Cancer Genome Atlas (TCGA) and used the least absolute shrinkage and selection operator (LASSO) Cox proportional hazards model (iteration = 1000) to develop a IRLP prognostic signature. The area under curve (AUC) was used to assess the prognosis predictive power. The multivariate Cox regression analysis was performed to identify whether this signature was an independent prognostic factor. The immune cell infiltration analysis was performed between the two risk groups. Last, molecular experiments were performed to explore LINC01082 is involved in the development of GC.

Results: We acquired lncRNA expression profiles and used the LASSO Cox model to develop an 18-IRLP signature with a strong prognostic predictive power. The 5-year AUC values of the training, validation, and overall TCGA datasets were 0.77, 0.86, and 0.80, respectively. The different prognostic outcomes between the high- and low-risk groups were determined using our 18-IRLP signature. Moreover, our 18-IRLP signature was an independent prognostic factor as per the multivariate Cox regression analysis, and showed better prognostic evaluation than the traditional TNM staging system as well as other clinical features. We also found differences in cancer-associated fibroblast and macrophage M2 infiltration and the expression of PD-L1, CTLA4, LAG3, and HLA were also observed between the two risk groups (P < 0.05). Analysis of biological functions revealed that target genes of the lncRNAs in the IRLP signature were enriched in focal adhesion and regulation of actin cytoskeleton. Finally, as one of significant candidates of IRLP signature, overexpression of LINC01082 suppressed the invasion ability of GC cells as well as PD-L1 expression profiles.

Conclusions: Our novel 18-IRLP signature provides new insights regarding immunological biomarkers, imparts a better understanding of the tumor immune microenvironment, and can be used for predicting prognosis and evaluating immune response in GC.
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http://dx.doi.org/10.1186/s12935-022-02493-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8832759PMC
February 2022

PGF2-FP Receptor Ameliorates Senescence of VSMCs in Vascular Remodeling by Src/PAI-1 Signal Pathway.

Oxid Med Cell Longev 2022 27;2022:2908261. Epub 2022 Jan 27.

The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China.

Senescence in vascular smooth muscle cells (VSMCs) is involved in vascular remodeling of aged mice. ProstaglandinF2 (PGF2-) FP receptor plays a critical role in cardiovascular diseases (CVDs), hypertension, and cardiac fibrosis. However, its role in senescence-induced arteriosclerosis is yet to be fully elucidated. In this study, we found that FP receptor expression increased in aged mouse aortas and senescence VSMCs. FP receptor gene silencing can ameliorate vascular aging and inhibit oxidative stress, thereby reducing the expression of PAI-1, inhibiting the activation of MMPs, and ultimately improving the excessive deposition of ECM and delaying the process of vascular fibrosis. FP receptor could promote VSMC senescence by upregulated Src/PAI-1 signal pathway, and inhibited FP receptor/Src/PAI-1 pathway could ameliorate VSMCs aging in vitro, evidenced by the decrease of senescence-related proteins P16, P21, P53, and GLB1 expressions. These results suggested that FP receptor is a promoter of vascular aging, by inducing cellular aging, oxidative stress, and vascular remodeling via Src and PAI-1 upregulation.
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http://dx.doi.org/10.1155/2022/2908261DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8813271PMC
March 2022

Increased expression of HOXA11-AS attenuates endometrial decidualization in recurrent implantation failure patients.

Mol Ther 2022 04 31;30(4):1706-1720. Epub 2022 Jan 31.

Center for Reproductive Medicine, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, No. 845 Lingshan Road, Pudong New Ddistrict, Shanghai 200135, China; Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai 200135, China. Electronic address:

Endometrial decidualization is a prerequisite for implantation, and impaired decidualization is associated with recurrent implantation failure (RIF). Coding genes of the HOX family have been clarified as critical regulators in endometrial decidualization, but the role of long non-coding RNAs (lncRNAs) in the HOX gene family has yet to be determined. The aim of this study was to clarify the possible roles of lncRNAs in the HOX gene family in decidualization. In this study, we identified that HOXA11-AS was the most reduced lncRNA in the HOX family in the human endometrium during the window of implantation, and it was elevated in RIF patients. Mechanistically, HOXA11-AS negatively regulated decidualization through competitive interaction with PTBP1, an RNA-binding protein. Binding of PTBP1 to HOXA11-AS limited PTBP1 availability to regulate PKM1/2 alternative splicing, resulting in enhanced PKM1 and diminished PKM2 expression, thus attenuating decidualization. The pattern of high HOXA11-AS expression and impaired PKM2 splicing was consistently observed in RIF patients. Collectively, our study indicates that the increase of HOXA11-AS is detrimental to endometrial decidualization, likely contributing to RIF. Our study may shed light on the pathogenesis and treatment of RIF.
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http://dx.doi.org/10.1016/j.ymthe.2022.01.036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9077377PMC
April 2022

Flavopiridol Mitigates the Progression of Monocrotaline-Induced Pulmonary Hypertension in Rats by Targeting Cyclin-Dependent Kinase 9.

Cardiovasc Drugs Ther 2022 Jan 28. Epub 2022 Jan 28.

Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Purpose: To investigate the role of cyclin-dependent kinase 9 (CDK9) and the therapeutic potential of a CDK9 inhibitor (flavopiridol) in monocrotaline (MCT)-induced pulmonary hypertension (PH).

Methods: For the in vivo experiments, rats with PH were established by a single intraperitoneal injection of MCT (60 mg/kg). After 2 weeks of MCT injection, rats were then treated with flavopiridol (5 mg/kg, i.p., twice a week) or vehicle for 2 weeks. For the in vitro experiments, human pulmonary artery smooth muscle cells (HPASMCs) were treated with flavopiridol (0.025-1 μM) or vehicle under hypoxic conditions. Hemodynamic recording, right ventricle histology, lung histology, and pulmonary arterial tissue isolation were performed. The expression levels of CDK9, RNA polymerase II, c-Myc, Mcl-1, and survivin were determined by qRT-PCR and western blotting, and the proliferation and apoptosis of rat pulmonary arterial tissues and/or HPASMCs were also assayed.

Results: Compared to the control group, CDK9 was upregulated in pulmonary arterial tissues from MCT-induced PH rats and hypoxic cultured HPASMCs. Upregulation of CDK9 was associated with enhanced phosphorylation of the C-terminal domain (CTD) of RNA polymerase II (RNA pol II) at serine-2 (Ser-2), promoting the expression of prosurvival and antiapoptotic proteins (c-Myc, Mcl-1, and survivin). Furthermore, treatment with flavopiridol (5 mg/kg) significantly alleviated pulmonary artery remodeling and partially reversed the progression of MCT-induced PH. Consistently, flavopiridol (0.5 μM) treatment decreased the proliferation and induced the apoptosis of cultured HPASMCs under hypoxic conditions. As a result of CDK9 inhibition and subsequent inhibition of RNA pol II CTD phosphorylation at Ser-2, flavopiridol decreased c-Myc, Mcl-1, and survivin expression in isolated pulmonary small arteries, leading to cell growth inhibition and apoptosis.

Conclusion: Flavopiridol mitigates the progression of MCT-induced PH in rats by targeting CDK9.
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http://dx.doi.org/10.1007/s10557-021-07285-wDOI Listing
January 2022
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