Publications by authors named "Hui Peng"

961 Publications

Clinical Eosinophil-Associated Genes can Serve as a Reliable Predictor of Bladder Urothelial Cancer.

Front Mol Biosci 2022 22;9:963455. Epub 2022 Jul 22.

The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China.

Numerous studies have shown that infiltrating eosinophils play a key role in the tumor progression of bladder urothelial carcinoma (BLCA). However, the roles of eosinophils and associated hub genes in clinical outcomes and immunotherapy are not well known. BLCA patient data were extracted from the TCGA database. The tumor immune microenvironment (TIME) was revealed by the CIBERSORT algorithm. Candidate modules and hub genes associated with eosinophils were identified by weighted gene co-expression network analysis (WGCNA). The external GEO database was applied to validate the above results. TIME-related genes with prognostic significance were screened by univariate Cox regression analysis, lasso regression, and multivariate Cox regression analysis. The patient's risk score (RS) was calculated and divided subjects into high-risk group (HRG) and low-risk group (LRG). The nomogram was developed based on the risk signature. Models were validated receiver operating characteristic (ROC) curves and calibration curves. Differences between HRG and LRG in clinical features and tumor mutational burden (TMB) were compared. The Immune Phenomenon Score (IPS) was calculated to estimate the immunotherapeutic significance of RS. Half-maximal inhibitory concentrations (IC50s) of chemotherapeutic drugs were predicted by the pRRophetic algorithm. 313 eosinophil-related genes were identified by WGCNA. Subsequently, a risk signature containing 9 eosinophil-related genes () was finally developed multiplex analysis and screening. Age ( < 0.001), grade ( < 0.001), and RS ( < 0.001) were independent predictors of survival in BLCA patients. Based on the calibration curve, our risk signature nomogram was confirmed as a good predictor of BLCA patients' prognosis at 1, 3, and 5 years. The association analysis of RS and immunotherapy indicated that low-risk patients were more credible for novel immune checkpoint inhibitors (ICI) immunotherapy. The chemotherapeutic drug model suggests that RS has an effect on the drug sensitivity of patients. In conclusion, the eosinophil-based RS can be used as a reliable clinical predictor and provide insights into the precise treatment of BLCA.
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http://dx.doi.org/10.3389/fmolb.2022.963455DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9353774PMC
July 2022

Ultrahigh Ferroelectric and Piezoelectric Properties in BiFeO-BaTiO Epitaxial Films Near Morphotropic Phase Boundary.

ACS Appl Mater Interfaces 2022 Aug 5. Epub 2022 Aug 5.

Key Laboratory of Polar Materials and Devices, Ministry of Education, Department of Electronics, East China Normal University, Shanghai 200241, China.

Ferroelectric solid solutions with composition near the morphotropic phase boundary (MPB) have gained extensive attention recently due to their excellent ferroelectric and piezoelectric properties. Here, we have demonstrated a strategy to realize the controllable preparation of BiFeO-BaTiO (BF-BT) epitaxial films near the MPB. A series of high-quality BF-BT films were fabricated by pulsed laser deposition via adjusting oxygen partial pressure (PO) using a BF-BT ceramic target. A continuous transition from rhombohedral to tetragonal phase was observed upon increasing PO. Particularly, the film with a pure tetragonal phase exhibited a large remnant polarization of ∼90.6 μC/cm, while excellent piezoelectric performance with an ultrahigh strain (∼0.48%) was obtained in the film with coexisting rhombohedral and tetragonal phases. The excellent ferroelectric and piezoelectric properties endow the BF-BT system near the MPB with great application prospects in lead-free electronic devices.
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http://dx.doi.org/10.1021/acsami.2c09062DOI Listing
August 2022

Ammonium-Modified Synthesis of Vanadium Sulfide Nanosheet Assemblies toward High Sodium Storage.

ACS Nano 2022 Aug 1. Epub 2022 Aug 1.

Research Center of Materials Science, Beijing Key Laboratory of Construction Tailorable Advanced Functional Materials and Green Applications, Beijing Institute of Technology, Beijing 100081, China.

The weak van der Waals interactions of the one-dimensional (1D) chainlike VS crystal structure can enable fast charge-transfer kinetics in metal ion batteries, but its potential has been rarely exploited in depth. Herein, a thermodynamics-driven morphology manipulation strategy is reported to tailor VS nanosheets into 3D hierarchical self-assembled architectures including nanospheres, hollow nanospheres, and nanoflowers. The ultrathin VS nanosheets are generated via 2D anisotropic growth by the strong driving force of coordination interaction from ammonium ions under microwave irradiation and then evolve into 3D sheet-assembled configurations by adjusting the thermodynamic factors of temperature and reaction time. The as-synthesized VS nanomaterials present good electrochemical performances as the anode materials for sodium-ion batteries. In particular, the hollow VS nanospheres show a specific capacity of 1226.7 mAh g at 200 mA g current density after 100 cycles. The hierarchical nanostructures with large specific surface area and structural stability can overcome the difficulty of sodium ions embedding into the bulk material interior and provide more reactive materials at the same material mass loading compared with other morphologies. Both experiment and DFT calculations suggest that VS nanosheets reduce reaction kinetic impediment of sodium ion in battery operating. This work demonstrates a way of the morphological design of 2D VS nanosheets and application in sodium ion storage.
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http://dx.doi.org/10.1021/acsnano.2c05232DOI Listing
August 2022

HO-NH-Induced Emission Modulation in Sb-Doped (NH)InCl·HO.

Inorg Chem 2022 Aug 25;61(31):12406-12414. Epub 2022 Jul 25.

Guangxi Key Lab of Processing for Nonferrous Metals and Featured Materials and Key Lab of New Processing Technology for Nonferrous Metals and Materials, Ministry of Education; School of Resources, Environmental and Materials, Guangxi University, Nanning 530004, China.

Lead-based metal halide perovskites have received widespread attention for their promising application prospects in the field of lighting and display due to their excellent optical properties. However, the toxicity of lead may hinder their further commercial application. Herein, a zero-dimensional (0D) metal halide (NH)InCl·HO with an orthorhombic structure and the space group was produced. With doping with Sb, these products exhibit one highly efficient and wide yellow emission band (∼450-850 nm) in their photoluminescence (PL) spectra, which covers almost the entire visible spectral range at room temperature; however, they give two emission bands with long decay lifetimes (microseconds) at low temperature. Temperature-dependent steady-state PL, transient PL spectroscopy, temperature-dependent Raman spectra characterization, and theoretical band structure calculations confirm that the dual-band emission at low temperature originates from the dual vibronic levels of the self-trapped exciton (STE) in the hole-vibration state, whose vibration energy is related to the HO-NH connection in the valence band. This result proves that the vibronic state in STE formation involves both electrons and holes in the excited states, the opposite of this happens in the electron-vibration band in most perovskite halides. These results provide new insight into the luminescent mechanism of Sb in halide perovskites, especially used for emission color modulation by the temperature-dependent electron- or hole-vibration processes.
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http://dx.doi.org/10.1021/acs.inorgchem.2c01856DOI Listing
August 2022

The omega-3 hydroxy fatty acid 7()-HDHA is a high-affinity PPARα ligand that regulates brain neuronal morphology.

Sci Signal 2022 Jul 5;15(741):eabo1857. Epub 2022 Jul 5.

Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada.

The nuclear receptor peroxisome proliferator-activated receptor alpha (PPARα) is emerging as an important target in the brain for the treatment or prevention of cognitive disorders. The identification of high-affinity ligands for brain PPARα may reveal the mechanisms underlying the synaptic effects of this receptor and facilitate drug development. Here, using an affinity purification-untargeted mass spectrometry (AP-UMS) approach, we identified an endogenous, selective PPARα ligand, 7()-hydroxy-docosahexaenoic acid [7()-HDHA]. Results from mass spectrometric detection of 7()-HDHA in mouse and rat brain tissues, time-resolved FRET analyses, and thermal shift assays collectively revealed that 7()-HDHA potently activated PPARα with an affinity greater than that of other ligands identified to date. We also found that 7()-HDHA activation of PPARα in cultured mouse cortical neurons stimulated neuronal growth and arborization, as well as the expression of genes associated with synaptic plasticity. The findings suggest that this DHA derivative supports and enhances neuronal synaptic capacity in the brain.
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http://dx.doi.org/10.1126/scisignal.abo1857DOI Listing
July 2022

Efficacy of Qihuang decoction on enteric nervous system in rats after gastrectomy.

J Tradit Chin Med 2022 Aug;42(4):556-564

Department of General Surgery, First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei 230031, China.

Objective: To investigate the influence of Qihuang decoction on enteric nervous system after gastrectomy in rats.

Methods: The morphology, distribution and number of intestinal neurons in enteric nervous system (ENS) were observed by immunofluorescence labeling and confocal laser scanning microscopy. Reverse transcription-polymerase chain reaction and Western blot were used to detect the mRNA and protein expression of intestinal neurotransmitters and corresponding receptors in ENS.

Results: The morphology and distribution of enteric neurons in ENS were changed after gastrectomy, and these neurons in Qihuang decoction group were similar with that of sham operation group. The number of ACh and SP positive neurons, mRNA and protein expression of excitatory neurotransmitters (AChE, SP) and receptors (M3R, NK1R) were decreased after gastrectomy. And the intervention of Qihuang decoction could increase the number of ACh and SP positive neurons and promote the expression of their mRNA and protein. For vasoactive intestinal peptide (VIP) and nitric oxide synthase (NOS), the number of neurons and mRNA and protein expression of inhibitory neurotransmitters (VIP and NOS) and receptors (VIP2R) were increased after gastrectomy. And these rising indexes fall back after the intervention of Qihuang decoction. Besides, the intestinal propulsion rate in QH group was significantly increased than that in SEN and IEN group.

Conclusions: These experimental results showed that after gastrectomy, early intervention with Qihuang decoction in small intestine will contribute to the postoperative recovery of enteric nervous system and intestinal propulsion rate, and consequently enhance gastrointestinal motility.
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http://dx.doi.org/10.19852/j.cnki.jtcm.20220519.004DOI Listing
August 2022

NRF2/PGC-1α-mediated mitochondrial biogenesis contributes to T-2 toxin-induced toxicity in human neuroblastoma SH-SY5Y cells.

Toxicol Appl Pharmacol 2022 Jul 13;451:116167. Epub 2022 Jul 13.

Center for Disease Control and Prevention, Chinese PLA, 20 Dongdajie Street, Fengtai District, Beijing 100071, China; School of Public Health, China Medical University, 77 Puhe Road, Shenyang North New area, Shenyang 110122, China. Electronic address:

The T-2 toxin is a highly toxic trichothecene mycotoxin that would cause serious toxicity in humans and animals. Recent studies suggest that the central nervous system (CNS) is susceptible to T-2 toxin, which can easily cross the blood-brain barrier, accumulate in brain tissues, and cause neurotoxicity. The growing evidence indicates that oxidative damage and mitochondrial dysfunction play a critical role in T-2 toxin-induced neurotoxicity, but the mechanisms are still poorly understood. Our present study showed that T-2 toxin decreased cell viability and increased lactate dehydrogenase leakage in human neuroblastoma SH-SY5Y cells in a concentration- and time-dependent manner. T-2 toxin elicited prominent oxidative stress and mitochondrial dysfunction, as evidenced by the promotion of cellular reactive oxygen species generation, disruption of the mitochondrial membrane potential, depletion of glutathione and reduction of the cellular ATP content. T-2 toxin impaired mitochondrial biogenesis, including decreased mitochondrial DNA copy number and affected the nuclear factor erythroid 2 related factor 2 (NRF2) / peroxisome proliferator-activated receptor γ coactivator 1 alpha (PGC-1α) pathway by upregulating NRF2 mRNA and protein expression while inhibiting the expression of PGC-1α, nuclear respiratory factor (NRF1) and mitochondrial transcription factor A (TFAM). NRF2 knockdown was found to significantly exacerbate T-2 toxin-induced cytotoxicity, oxidative stress, and mitochondrial dysfunction, as well as aggravate mitochondrial biogenesis impairment. NRF2 knockdown compromised T-2 toxin-induced upregulation of NRF2, but augmented the inhibition of PGC-1α, NRF1, and TFAM by T-2 toxin. Taken together, these findings suggest that T-2 toxin-induced oxidative stress and mitochondrial dysfunction in SH-SY5Y cells, at least in part by, NRF2/PGC-1α pathway-mediated mitochondrial biogenesis.
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http://dx.doi.org/10.1016/j.taap.2022.116167DOI Listing
July 2022

RHEB is a potential therapeutic target in T cell acute lymphoblastic leukemia.

Biochem Biophys Res Commun 2022 09 30;621:74-79. Epub 2022 Jun 30.

Division of Molecular Genetics, Cancer and Stem Cell Research Program, Cancer Research Institute, Kanazawa University, Kakuma-machi, Kanazawa, Ishikawa, 920-1192, Japan; WPI Nano Life Science Institute (WPI-Nano LSI), Kanazawa University, Kakuma-machi, Kanazawa, Ishikawa, 920-1192, Japan. Electronic address:

T cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy of immature T lymphocytes. Although various therapeutic approaches have been developed, refractoriness of chemotherapy and relapse cause a poor prognosis of the disease and further therapeutic strategies are required. Here, we report that Ras homolog enriched in brain (RHEB), a critical regulator of mTOR complex 1 activity, is a potential target for T-ALL therapy. In this study, we established an sgRNA library that comprehensively targeted mTOR upstream and downstream pathways, including autophagy. CRISPR/Cas9 dropout screening revealed critical roles of mTOR-related molecules in T-ALL cell survival. Among the regulators, we focused on RHEB because we previously found that it is dispensable for normal hematopoiesis in mice. Transcriptome and metabolic analyses revealed that RHEB deficiency suppressed de novo nucleotide biosynthesis, leading to human T-ALL cell death. Importantly, RHEB deficiency suppressed tumor growth in both mouse and xenograft models. Our data provide a potential strategy for efficient therapy of T-ALL by RHEB-specific inhibition.
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http://dx.doi.org/10.1016/j.bbrc.2022.06.089DOI Listing
September 2022

A Zero-Dimensional Organic Lead Bromide of (TPA)PbBr Single Crystal with Bright Blue Emission.

Nanomaterials (Basel) 2022 Jun 28;12(13). Epub 2022 Jun 28.

Guangxi Key Lab of Processing for Nonferrous Metals and Featured Materials and Key Lab of New Processing Technology for Nonferrous Metals and Materials, Ministry of Education, School of Resources, Environments and Materials, Guangxi University, Nanning 530004, China.

Blue-luminescence materials are needed in urgency. Recently, zero-dimensional (0D) organic metal halides have attractive much attention due to unique structure and excellent optical properties. However, realizing blue emission with near-UV-visible light excitation in 0D organic metal halides is still a great challenge due to their generally large Stokes shifts. Here, we reported a new (0D) organic metal halides (TPA)PbBr single crystal (TPA = tetrapropylammonium cation), in which the isolated [PbBr] tetrahedral clusters are surrounded by organic ligand of TPA, forming a 0D framework. Upon photoexcitation, (TPA)PbBr exhibits a blue emission peaking at 437 nm with a full width at half-maximum (FWHM) of 50 nm and a relatively small Stokes shift of 53 nm. Combined with density functional theory (DFT) calculations and spectral analysis, it is found that the observed blue emission in (TPA)PbBr comes from the combination of free excitons (FEs) and self-trapped exciton (STE), and a small Stokes shift of this compound are caused by the small structure distortion of [PbBr] cluster in the excited state confined by TPA molecules, in which the multi-phonon effect take action. Our results not only clarify the important role of excited state structure distortion in regulating the STEs formation and emission, but also focus on 0D metal halides with bright blue emission under the near-UV-visible light excitation.
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http://dx.doi.org/10.3390/nano12132222DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9268179PMC
June 2022

Calycosin Improves Intestinal Mucosal Barrier Function after Gastrectomy in Rats through Alleviating Bacterial Translocation, Inflammation, and Oxidative Stress.

Evid Based Complement Alternat Med 2022 26;2022:7412331. Epub 2022 Jun 26.

Department of General Surgery, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei 230031, Anhui, China.

Objective: Calycosin is the main bioactive extract of with anti-inflammation, antioxidant, and anticancer properties. Here, our study evaluated the protective effects and mechanisms of calycosin on intestinal mucosal barrier under gastrectomy.

Methods: After receiving gastrectomy, the rats were administrated with 20 mg/kg, 40 mg/kg, or 80 mg/kg calycosin. Endotoxin, bacterial translocation, and intestinal bacterial flora were assayed. Intestinal injury was detected via hematoxylin and eosin staining. Tight junction indicators (occludin, claudin, and ZO-1) and apoptotic proteins (Bax, Bcl-2, and cleaved caspase 3) were examined in intestinal tissues. Inflammatory indicators (IL-1, IL-6, and TNF-) were examined in serum or intestinal specimens via ELISA. Apoptosis was assessed via TUNEL staining. IgA + B cells in intestinal tissues and sIgA in intestinal lumen were examined through immunohistochemistry and ELISA, respectively. Oxidative stress indicators (TSH, SOD, CAT, GSH-Px, and MDA) were also detected via ELISA.

Results: Our results showed that calycosin administration decreased endotoxin levels in peripheral blood, intestine, and portal vein blood; lowered the bacterial translocation ratio; and regained the balance among intestinal bacterial flora (comprising bifidobacterium, lactic acid bacillus, enterobacter, enterococcus, aerobic bacteria, and anaerobic bacteria) in the rats with gastrectomy. After calycosin treatment, intestinal mucosal damage of the rats with gastrectomy was ameliorated, with the increase in expression of tight junction proteins. Additionally, calycosin reduced intestinal inflammation, apoptosis, secretion of sIgA, and oxidative stress in the rats with gastrectomy.

Conclusion: Altogether, our findings demonstrate that calycosin may improve intestinal mucosal barrier function under gastrectomy via reducing bacterial translocation, inflammation, and oxidative stress.
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http://dx.doi.org/10.1155/2022/7412331DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9251107PMC
June 2022

Exploring the Positive User Experience Possibilities Based on Product Emotion Theory: A Beverage Unmanned Retail Terminal Case.

Front Psychol 2022 16;13:889664. Epub 2022 Jun 16.

Intelligent Interaction Design Laboratory, School of Design, Jiangnan University, Wuxi, China.

Since the last century, user experience has been regarded as a key concept in the process of product and service design. With the development of positive psychology, the transformation from negative to positive user experience has also taken place in the field of user experience; it emphasizes exploring the future possibility of positive user experience rather than just solving existing problems. Based on the research and analysis of existing literature, this study makes it clear that positive user experience research should be based on the "positive experience," and arousing a positive emotion is conducive to improving positive user experience. On this basis, the product emotion theory is applied to the analysis process of "positive experience." Through word frequency screening, thematic analysis, and correlation calculation, the relationship between product stimulus (object, activity, and identity) and user concern (goal, attitude, and standard) based on positive "user comments" is constructed, and positive user experience is understood from multiple levels. Based on the comment score, the positive user experience interval is divided in order to clarify the improvement direction. Finally, taking the "Angel Orange" unmanned retail terminal as an example, this study carried out an empirical analysis. As an exploratory study, this study can provide some insights into the quantitative research process of positive user experience design that evokes positive emotions from a user's "positive experience" story.
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http://dx.doi.org/10.3389/fpsyg.2022.889664DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9244544PMC
June 2022

Salvianolic acid B dry powder inhaler for the treatment of idiopathic pulmonary fibrosis.

Asian J Pharm Sci 2022 May 30;17(3):447-461. Epub 2022 Apr 30.

State Key Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China.

Idiopathic pulmonary fibrosis (IPF) is a serious and fatal pulmonary inflammatory disease with an increasing incidence worldwide. The drugs nintedanib and pirfenidone, are listed as conditionally recommended drugs in the "Evidence-Based Guidelines for the Diagnosis and Treatment of Idiopathic Pulmonary Fibrosis". However, these two drugs have many adverse reactions in clinical application. Salvianolic acid B (Sal B), a water-soluble component of Salvia miltiorrhiza, could alleviate bleomycin-induced peroxidative stress damage, and prevent or delay the onset of IPF by regulating inflammatory factors and fibrotic cytokines during the disease's progression. However, Sal B is poorly absorbed orally, and patient compliance is poor when administered intravenously. Therefore, there is an urgent need to find a new non-injection route of drug delivery. In this study, Sal B was used as model drug and l-leucine (LL) as excipient to prepare Sal B dry powder inhaler (Sal B-DPI) by spray drying method. Modern preparation evaluation methods were used to assess the quality of Sal B-DPI. Sal B-DPI is promising for the treatment of IPF, according to studies on pulmonary irritation evaluation, and pharmacodynamics, metabolomics, pharmacokinetics, and lung tissue distribution.
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http://dx.doi.org/10.1016/j.ajps.2022.04.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9237582PMC
May 2022

Effects of Xiao Chengqi Formula on Slow Transit Constipation by Assessing Gut Microbiota and Metabolomics Analysis and .

Front Pharmacol 2022 8;13:864598. Epub 2022 Jun 8.

Department of Coloproctology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

The Xiao Chengqi (XCQ) formula is a newly constituted traditional Chinese medicine prescription in the treatment of intestinal motility deficiency and is effective in patients with slow transit constipation (STC). XCQ formula was reconstructed based on a "Chengqi" decoction. Astragali Radix, Angelicae Sinensis Radix, and cooked ground Salviae Miltiorrhizae Radix et Rhizoma were added to the prescription to enhance. An STC rat model was constructed and treated with the formula to understand the detailed mechanism by which XCQ promotes intestinal peristalsis. The effects of the XCQ formula on intestinal microflora and metabolic levels and the possible molecular mechanism of its regulation were explored using 16S rDNA sequencing, metabolomics sequencing, and tissue RNA sequencing. The results showed a significant decrease in the abundance of spp. in the feces of STC rats, a significant decrease in the content of butyl aminobenzene (BAB) in feces, and an increase in the number of interstitial cells of Cajal (ICC) in the colon of STC rats. Furthermore, and experiments revealed that BAB could activate IL-21R on the ICC surface, upregulate the phosphorylation of the downstream molecules STAT3 and ERK, and inhibit loperamide-induced ICC apoptosis. Therefore, the XCQ formula can improve the defecation status of patients with STC by protecting ICC activity, promoting the colonization of spp to promote peristalsis and increasing the BAB content after metabolism.
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http://dx.doi.org/10.3389/fphar.2022.864598DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9237644PMC
June 2022

Biomechanical Comparison of Six Different Root-Analog Implants and the Conventional Morse Taper Implant by Finite Element Analysis.

Front Genet 2022 13;13:915679. Epub 2022 Jun 13.

Department of Oral and Maxillofacial Surgery, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, China.

Taper implants differ greatly from anatomical teeth in shape. In this study, seven three-dimensional finite element models were established, including a conventional taper implant and six root-analog implants with different root numbers and shapes. Vertical, horizontal, and oblique instantaneous loads of 100 N were applied to the models to obtain stress distribution in the implant, mucosa, cortical bone, and cancellous bone. ANSYS was used to perform the analysis under hypothetical experimental conditions. We find the stresses in all the implants and surrounding tissues varied by loading direction, the sequence of stress magnitude is vertical load, oblique load, and then horizontal load. The maximum stress values in root-analog implants were significantly less than in the taper implant. Moreover, stress distribution in the former was equalized contrary to the concentrated stress in the latter. Root-analog implants with different root geometry also revealed a pattern: stresses in multiple-root implant models were lower than those in single-root implants under the same load. The implant with a long and rounded root distributed the stress more uniformly, and it was mainly concentrated on the implant itself and cancellous bone. However, the opposite effect was observed in the short implant on mucosa and cortical bone. The root geometry of anatomical teeth can modify their functions. A uniform-shaped implant can hardly meet their functional requirements. Thus, the root-analog implant could be a possible solution.
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http://dx.doi.org/10.3389/fgene.2022.915679DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9234945PMC
June 2022

Development and Validation of a Clinical Prediction Model for Complicated Appendicitis in the Elderly.

Front Surg 2022 9;9:905075. Epub 2022 Jun 9.

General surgery department, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, China.

Background: For elderly patients with mild clinical symptoms of uncomplicated appendicitis(UA), non-surgical treatment has been shown to be feasible, whereas emergency surgical treatment is recommended in elderly patients with complicated appendicitis(CA), but it is still challenging to accurately distinguish CA and UA before treatment. This study aimed to develop a predictive model to assist clinicians to quickly determine the type of acute appendicitis.

Methods: We retrospectively studied the clinical data of elderly patients with acute appendicitis who visited the First Affiliated Hospital of Anhui University of Traditional Chinese Medicine from January 2012 to January 2022. The patients were divided into UA group and CA group, and the general conditions, medical history, physical examination, laboratory examination and imaging examination were compared between the two groups, and SPSS 26.0 and R 4.0.2 software were used to establish CA clinic. Predict the model, and validate it internally.

Results: The clinical data of 441 elderly patients with acute appendicitis were collected, 119 patients were excluded due to incomplete clinical data or other diseases. Finally, 332 patients were included in the study and divided into UA group ( = 229) and CA group ( = 103). By analyzing the clinical data of the two groups of patients, the duration of abdominal pain [OR = 1.094, 95% CI (1.056-1.134)], peritonitis [OR = 8.486, 95% CI (2.017-35.703))] and total bilirubin [OR = 1.987, 95% CI (1.627-2.426)] were independent predictors of CA (all < 0.01). The model's Area Under Curve(AUC) = 0.985 (95% CI, 0.975-0.994). After internal verification by Bootstrap method, the model still has high discriminative ability (AUC = 0.983), and its predicted CA curve is still in good agreement with the actual clinical CA curve.

Conclusion: We found that a clinical prediction model based on abdominal pain duration, peritonitis, and total bilirubin can help clinicians quickly and effectively identify UA or CA before treatment of acute appendicitis in the elderly, so as to make more scientific clinical decisions.
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http://dx.doi.org/10.3389/fsurg.2022.905075DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9218209PMC
June 2022

Maternal One-Carbon Supplement Reduced the Risk of Non-Alcoholic Fatty Liver Disease in Male Offspring.

Nutrients 2022 Jun 19;14(12). Epub 2022 Jun 19.

Department of Nutrition, Texas A&M University, College Station, TX 77840, USA.

Recent studies have suggested that prevention of obesity and non-alcoholic fatty liver disease (NAFLD) should start with maternal dietary management. We previously reported disrupted methionine cycle, associated with NAFLD, in male offspring liver due to maternal high-fat (HF) diet, thus we hypothesize that maternal one-carbon supplement may reduce the risk of NAFLD in offspring via the normalizing methionine cycle. To test it, female mice (F0) were exposed to either a maternal normal-fat diet (NF group) a maternal HF diet (HF group), or a maternal methyl donor supplement (H1S or H2S group) during gestation and lactation. The offspring male mice (F1) were exposed to a postweaning HF diet to promote NAFLD. While the HF offspring displayed obesity, glucose intolerance and hepatic steatosis, the H1S and H2S offspring avoided hepatic steatosis. This phenotype was associated with the normalization of the methionine cycle and the restoration of L-carnitine and AMPK activity. Furthermore, maternal HF diet induced epigenetic regulation of important genes involved in fatty acid oxidation and oxidative phosphorylation via DNA methylation modifications, which were recovered by maternal one-carbon supplementation. Our study provides evidence that maternal one-carbon supplement can reverse/block the adverse effects of maternal HF diet on promoting offspring NAFLD, suggesting a potential nutritional strategy that is administered to mothers to prevent NAFLD in the offspring.
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http://dx.doi.org/10.3390/nu14122545DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9228996PMC
June 2022

Single-cell transcriptomics reveals immune dysregulation mediated by IL-17A in initiation of chronic lung injuries upon real-ambient particulate matter exposure.

Part Fibre Toxicol 2022 06 23;19(1):42. Epub 2022 Jun 23.

Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Toxicology, School of Public Health, Sun Yat-Sen University, Guangzhou, 510080, China.

Background: Long-term exposure to fine particulate matter (PM) increases susceptibility to chronic respiratory diseases, including inflammation and interstitial fibrosis. However, the regulatory mechanisms by which the immune response mediates the initiation of pulmonary fibrosis has yet to be fully characterized. This study aimed to illustrate the interplay between different cell clusters and key pathways in triggering chronic lung injuries in mice following PM exposure.

Results: Six-week-old C57BL/6J male mice were exposed to PM or filtered air for 16 weeks in a real-ambient PM exposure system in Shijiazhuang, China. The transcriptional profiles of whole lung cells following sub-chronic PM exposure were characterized by analysis of single-cell transcriptomics. The IL-17A knockout (IL-17A) mouse model was utilized to determine whether the IL-17 signaling pathway mediated immune dysregulation in PM-induced chronic lung injuries. After 16-week PM exposure, chronic lung injuries with excessive collagen deposition and increased fibroblasts, neutrophils, and monocytes were noted concurrent with a decreased number of major classes of immune cells. Single-cell analysis showed that activation of the IL-17 signaling pathway was involved in the progression of pulmonary fibrosis upon sub-chronic PM exposure. Depletion of IL-17A led to significant decline in chronic lung injuries, which was mainly triggered by reduced recruitment of myeloid-derived suppressor cells (MDSCs) and downregulation of TGF-β.

Conclusion: These novel findings demonstrate that immunosuppression via the IL-17A pathway plays a critical role in the initiation of chronic lung injuries upon sub-chronic PM exposure.
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http://dx.doi.org/10.1186/s12989-022-00483-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9219231PMC
June 2022

Decoding the transcriptome of denervated muscle at single-nucleus resolution.

J Cachexia Sarcopenia Muscle 2022 Jun 20. Epub 2022 Jun 20.

Nephrology Division, Department of Medicine, Baylor College of Medicine, Houston, TX, USA.

Background: Skeletal muscle exhibits remarkable plasticity under both physiological and pathological conditions. One major manifestation of this plasticity is muscle atrophy that is an adaptive response to catabolic stimuli. Because the heterogeneous transcriptome responses to catabolism in different types of muscle cells are not fully characterized, we applied single-nucleus RNA sequencing (snRNA-seq) to unveil muscle atrophy related transcriptional changes at single nucleus resolution.

Methods: Using a sciatic denervation mouse model of muscle atrophy, snRNA-seq was performed to generate single-nucleus transcriptional profiles of the gastrocnemius muscle from normal and denervated mice. Various bioinformatics analyses, including unsupervised clustering, functional enrichment analysis, trajectory analysis, regulon inference, metabolic signature characterization and cell-cell communication prediction, were applied to illustrate the transcriptome changes of the individual cell types.

Results: A total of 29 539 muscle nuclei (normal vs. denervation: 15 739 vs. 13 800) were classified into 13 nuclear types according to the known cell markers. Among these, the type IIb myonuclei were further divided into two subgroups, which we designated as type IIb1 and type IIb2 myonuclei. In response to denervation, the proportion of type IIb2 myonuclei increased sharply (78.12% vs. 38.45%, P < 0.05). Concomitantly, trajectory analysis revealed that denervated type IIb2 myonuclei clearly deviated away from the normal type IIb2 myonuclei, indicating that this subgroup underwent robust transcriptional reprogramming upon denervation. Signature genes in denervated type IIb2 myonuclei included Runx1, Gadd45a, Igfn1, Robo2, Dlg2, and Sh3d19 (P < 0.001). The gene regulatory network analysis captured a group of atrophy-related regulons (Foxo3, Runx1, Elk4, and Bhlhe40) whose activities were enhanced (P < 0.01), especially in the type IIb2 myonuclei. The metabolic landscape in the myonuclei showed that most of the metabolic pathways were down-regulated by denervation (P < 0.001), while some of the metabolic signalling, such as glutathione metabolism, was specifically activated in the denervated type IIb2 myonulei. We also investigated the transcriptomic alterations in the type I myofibres, muscle stem cells, fibro-adipogenic progenitors, macrophages, endothelial cells and pericytes and characterized their signature responses to denervation. By predicting the cell-cell interactions, we observed that the communications between myofibres and muscle resident cells were diminished by denervation.

Conclusions: Our results define the myonuclear transition, metabolic remodelling, and gene regulation networks reprogramming associated with denervation-induced muscle atrophy and illustrate the molecular basis of the heterogeneity and plasticity of muscle cells in response to catabolism. These results provide a useful resource for exploring the molecular mechanism of muscle atrophy.
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http://dx.doi.org/10.1002/jcsm.13023DOI Listing
June 2022

Research on Portal Venous Hemodynamics and Influencing Factors of Portal Vein System Thrombosis for Wilson's Disease after Splenectomy.

Front Surg 2022 30;9:834466. Epub 2022 May 30.

The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, China.

Objective: Splenectomy is one crucial solution for hypersplenism with portal hypertension. However, portal vein system thrombosis (PVST) caused by hemodynamic changes affects the prognosis of patients. We analyze the changes in portal vein hemodynamics following splenectomy for Wilson's disease combined with portal hypertension and the influencing factors that lead to PVST.

Methods: A retrospective cohort study was conducted, in which 237 Wilson's disease patients with hypersplenism underwent splenectomy. The hemodynamic indices of the portal vein were monitored before surgery and on the 1st, 7th, and 14th days around surgery. The patients were divided into PVST and non-PVST groups. The clinical factors were identified by univariate and multivariate logistic regression. The Logit was calculated according to the logistic regression prediction model, and the ROC curve for each independent factor was plotted.

Results: The portal vein velocity, flow, and inner diameter showed a downward trend around surgery, with statistically significant differences between each time point (< 0.01). The PVST incidence rate was 55.7%. Univariate analysis revealed that the platelet (PLT) levels on the postoperative 3rd and 7th days (= 0.001; < 0.001), D-dimer (D-D) on the postoperative 7th and 14th days (= 0.002; < 0.001), preoperative portal vein velocity, flow, diameter (< 0.001), and splenic vein diameter (< 0.001) were all statistically and significantly different between the two groups. Multivariate logistic regression revealed a significant increase in PLT on the postoperative 7th day (OR= 1.043, 95% CI, 1.027-1.060, < 0.001) and D-D on the postoperative 14th day (OR = 1.846, 95% CI, 1.400-2.435, < 0.001). Preoperative portal and splenic vein diameters (OR = 1.565, 95% CI, 1.213-2.019, = 0.001; OR = 1.671, 95% CI, 1.305-2.140, < 0.001) were the risk factors for PVST. However, preoperative portal vein velocity and flow (OR = 0.578, 95% CI, 0.409-0.818, = 0.002; OR= 0.987, 95% CI, 0.975-0.990, = 0.046) were protective factors for PVST. Logit was calculated using a logistic regression prediction model with a cut-off value of -0.32 and an area under receiver operating characteristic curve of 0.952 with 88.61% accuracy.

Conclusions: Splenectomy relieves portal hypertension by reducing the hemodynamics index. PVST is linked to multiple factors, including preoperative portal vein diameter, velocity, flow, and splenic vein diameter, especially PLT on the postoperative 7th day and D-D on the postoperative 14th day. The predictive model is accurate in predicting PVST.
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http://dx.doi.org/10.3389/fsurg.2022.834466DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9189385PMC
May 2022

A mechanosensitive lipolytic factor in the bone marrow promotes osteogenesis and lymphopoiesis.

Cell Metab 2022 Aug 14;34(8):1168-1182.e6. Epub 2022 Jun 14.

Department of Endocrinology, Endocrinology Research Center, Xiangya Hospital of Central South University, Changsha, Hunan 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, Hunan 410008, China; Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Hunan 410008, China. Electronic address:

Exercise can prevent osteoporosis and improve immune function, but the mechanism remains unclear. Here, we show that exercise promotes reticulocalbin-2 secretion from the bone marrow macrophages to initiate bone marrow fat lipolysis. Given the crucial role of lipolysis in exercise-stimulated osteogenesis and lymphopoiesis, these findings suggest that reticulocalbin-2 is a pivotal regulator of a local adipose-osteogenic/immune axis. Mechanistically, reticulocalbin-2 binds to a functional receptor complex, which is composed of neuronilin-2 and integrin beta-1, to activate a cAMP-PKA signaling pathway that mobilizes bone marrow fat via lipolysis to fuel the differentiation and function of mesenchymal and hematopoietic stem cells. Notably, the administration of recombinant reticulocalbin-2 in tail-suspended and old mice remarkably decreases bone marrow fat accumulation and promotes osteogenesis and lymphopoiesis. These findings identify reticulocalbin-2 as a novel mechanosensitive lipolytic factor in maintaining energy homeostasis in bone resident cells, and it provides a promising target for skeletal and immune health.
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http://dx.doi.org/10.1016/j.cmet.2022.05.009DOI Listing
August 2022

Stepwise responsive carboxymethyl chitosan-based nanoplatform for effective drug-resistant breast cancer suppression.

Carbohydr Polym 2022 Sep 2;291:119554. Epub 2022 May 2.

School of Life Sciences, Anhui Medical University, Hefei 230032, China; Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Medical University, Hefei 230032, China. Electronic address:

Efficient delivery systems for co-delivery of P-glycoprotein (P-gp) inhibitors and chemotherapeutic drugs are essential for inhibiting multi-drug resistance (MDR) breast cancers. Herein, we present a multi-functional carboxymethyl chitosan (CMC) based core-shell nanoplatform to co-deliver MDR1 gene-silenced small interfering RNA (siMDR1) and doxorubicin (DOX) for optimal combinatorial therapy. DOX is linked to CMC through a disulfide bond to model redox-responsive prodrug (CMC-DOX) as the inner core. siMDR1 is encapsulated in oligoethylenimine (OEI), which is electrostatically adsorbed on CMC-DOX as the pH-responsive sheddable shielding shell. AS1411 aptamer and GALA peptide functionalised hyaluronic acid (AHA/GHA) are provided on the surface for tumour-targeting and endo/lysosomal escape. The nanoplatform could stepwise release payloads with acid/redox triggered fashion. AHA effectively improves nanoplatform intracellular uptake and tumour accumulation. GHA facilitates cargos escape from endo/lysosomes to cytoplasm. The multi-functional nanoplatform provides 86.3 ± 2.2% siMDR1 gene silencing and significantly downregulates P-gp expression. Moreover, it ensures 55.7 ± 1.6% MCF-7/ADR cell apoptosis at a low concentration of DOX (30 μg/mL) in vitro and performs synergistic therapeutic effects suppressing tumour growth in vivo. Overall, the multi-functional CMC-based biopolymers can be efficient siRNA/drug co-delivery carriers for cancer chemotherapy.
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http://dx.doi.org/10.1016/j.carbpol.2022.119554DOI Listing
September 2022

Investigation of heparin-loaded poly(ethylene glycol)-based hydrogels as anti-thrombogenic surface coatings for extracorporeal membrane oxygenation.

J Mater Chem B 2022 07 6;10(26):4974-4983. Epub 2022 Jul 6.

Innovative Cardiovascular Engineering and Technology Laboratory, Critical Care Research Group, The Prince Charles Hospital, QLD, Australia.

Extracorporeal membrane oxygenation (ECMO), a critical life-sustaining tool, faces significant challenges for the maintenance of normal haemostasis due to the large volume of circulating blood continuously in contact with artificial surfaces, hyperoxia and excessive shear stresses of the extracorporeal circuit. From a biomaterials perspective, it has been hypothesised that drug eluting coatings composed of haemocompatible hydrogels loaded with an anticoagulant drug could potentially enhance the haemocompatibility of the circuit. Poly(ethylene glycol) (PEG) has been well established as a biocompatible and anti-fouling material with wide biomedical application. Unfractionated heparin is the most commonly used anticoagulant for ECMO. In the present study, the feasibility of using heparin-loaded PEG-based hydrogels as anti-thrombogenic surface coatings for ECMO was investigated. The hydrogels were synthesised by photopolymerisation using poly(ethylene glycol) diacrylate (PEGDA) as the crosslinking monomer and poly(ethylene glycol) methacrylate (PEGMA) as the hydrophilic monomer, with heparin loaded into the pre-gel solution. Factors which could affect the release of heparin were investigated, including the ratio of PEGDA/PEGMA, water content, loading level of heparin and the flow of fluid past the hydrogel. Our results showed that increased crosslinker content and decreased water content led to slower heparin release. The hydrogels with water contents of 60 wt% and 70 wt% could achieve a sustained heparin release by adjusting the ratio of PEGDA/PEGMA. The anticoagulation efficacy of the released heparin was evaluated by measuring the activated clotting time of whole blood. The hydrogels with desirable heparin release profiles were prepared onto poly(4-methyl-1-pentene) (PMP) films with the same chemical composition as the PMP ECMO membranes. The coatings showed sustained heparin release with a cumulative release of 70-80% after 7 days. Haemocompatibility tests demonstrated that PEG hydrogel coatings significantly reduced platelet adhesion and prolonged plasma recalcification time. These results suggest that heparin-loaded PEG hydrogels are potential anti-thrombogenic coatings for ECMO.
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http://dx.doi.org/10.1039/d2tb00379aDOI Listing
July 2022

AI based colorectal disease detection using real-time screening colonoscopy.

Precis Clin Med 2021 Jun 20;4(2):109-118. Epub 2021 May 20.

Department of Clinical Research Center, Dazhou Central Hospital, Dazhou 635000, China.

Colonoscopy is an effective tool for early screening of colorectal diseases. However, the application of colonoscopy in distinguishing different intestinal diseases still faces great challenges of efficiency and accuracy. Here we constructed and evaluated a deep convolution neural network (CNN) model based on 117 055 images from 16 004 individuals, which achieved a high accuracy of 0.933 in the validation dataset in identifying patients with polyp, colitis, colorectal cancer (CRC) from normal. The proposed approach was further validated on multi-center real-time colonoscopy videos and images, which achieved accurate diagnostic performance on detecting colorectal diseases with high accuracy and precision to generalize across external validation datasets. The diagnostic performance of the model was further compared to the skilled endoscopists and the novices. In addition, our model has potential in diagnosis of adenomatous polyp and hyperplastic polyp with an area under the receiver operating characteristic curve of 0.975. Our proposed CNN models have potential in assisting clinicians in making clinical decisions with efficiency during application.
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http://dx.doi.org/10.1093/pcmedi/pbab013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8982552PMC
June 2021

Long Noncoding RNA MIAT Regulates Hyperosmotic Stress-Induced Corneal Epithelial Cell Injury via Inhibiting the Caspase-1-Dependent Pyroptosis and Apoptosis in Dry Eye Disease.

J Inflamm Res 2022 2;15:3269-3283. Epub 2022 Jun 2.

Ophthalmology, Affiliated Hospital of Qingdao University, Qingdao, 266500, People's Republic of China.

Purpose: The biological role and mechanism of long noncoding RNA (lncRNA) myocardial infarction-associated transcript (MIAT) in dry eye remain to be illustrated. Pyroptosis is a noticeable form of inflammatory activation, which is characteristic of gasdermin D (GSDMD)-driven cell death. The present study was designed to explore the role of MIAT in pyroptosis and apoptosis induced by hyperosmolarity stress (HS) in human corneal epithelial cells (HCECs).

Methods: HCECs were cultured in 70-120 mM hyperosmotic medium for 24 h to create a dry eye model in vitro. The level of the pyroptosis marker GSDMD was measured, and the cell inflammatory response was evaluated by detecting IL-1β and IL-18 levels. Exogenous caspase-1 inhibitor Ac-YVAD-CHO was used. The pyroptosis in HCECs was examined by caspase-1 activity, immunofluorescent staining, and Western blotting. Flow cytometry was performed to test the apoptosis rate of HCECs. Cell migration and proliferation were detected. The expression of the lncRNA MIAT in HCECs was detected by quantitative real-time PCR. MIAT was knocked down by small interfering RNA (siRNA) transfection. The effects of caspase-1 inhibition on pyroptosis, apoptosis, migration, and proliferation were observed.

Results: HS promoted pyroptosis in HCECs by elevating caspase-1, GSDMD, and the active cleavage of GSDMD (N-terminal domain, N-GSDMD), and increased the release of IL-1β, IL-18, LDH and the rate of apoptosis, with reduced cell migration. These changes were prevented by the inhibition of caspase-1. The expression of MIAT was significantly increased in HCECs exposed to a hyperosmotic medium. Silencing MIAT increased the expression of GSDMD, caspase-1, and inflammatory chemokines IL-1β and IL-18, and promoted apoptosis while inhibiting migration and proliferation in HCECs.

Conclusion: The lncRNA MIAT is involved in HS-induced pyroptosis and apoptosis and the inflammatory response of HCECs and provides a new understanding of the pathogenesis of dry eye.
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http://dx.doi.org/10.2147/JIR.S361541DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9169976PMC
June 2022

Association of QTc Interval and V4-S Wave With Appropriate ICD Therapy in Hypertrophic Cardiomyopathy.

Front Cardiovasc Med 2022 12;9:882662. Epub 2022 May 12.

Cardiac Arrhythmia Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Background: Ventricular arrhythmias in patients with hypertrophic cardiomyopathy (HCM) may lead to sudden cardiac death (SCD). We aimed to investigate the relationship between electrocardiogram (ECG) indicators and the risk of appropriate implantable cardioverter-defibrillator (ICD) therapy in HCM.

Methods: The HCM patients receiving ICD implantation were enrolled consecutively. QT interval correction (QTc) was calculated using Bazett's formula. Long or deep S wave in V4 lead was defined as duration time >50 ms and/or voltage amplitude >0.6 mV. The endpoint in our study was at least one ICD appropriate therapy triggered by ventricular tachyarrhythmia (VT) or ventricular fibrillation (VF), including anti-tachyarrhythmia pacing (ATP) and electrical shock.

Results: A total of 149 patients with HCM (mean age 53 ± 14 years, male 69.8%) were studied. Appropriate ICD therapies occurred in 47 patients (31.5%) during a median follow-up of 2.9 years. Cox regression analysis showed that long or deep S wave in V4 lead [hazard ratio (HR) 1.955, 95% confidence interval (CI) 1.017-3.759, = 0.045] and QTc interval (HR 1.014, 95% CI 1.008-1.021, < 0.001) were independent risk factors for appropriate ICD therapy. The ROC showed that the optimal cut-off point value for the QTc interval to predict the appropriate ICD therapy was 464 ms, and the AUC was 0.658 (95% CI 0.544-0.762, = 0.002). The AUC for S wave anomalies in V4 lead was 0.608 (95% CI 0.511-0.706, = 0.034). We developed a new model that combined the QTc interval and S wave anomalies in V4 lead based on four patient groups. Patients with QTc ≥464 ms and long or deep V4-S wave had the highest risk of developing appropriate ICD therapy (log-rank < 0.0001). After adding QTc interval and V4-S wave anomalies into the HCM-risk-SCD model, the prediction effect of the new model was significantly improved, and the NRI was 0.302.

Conclusions: In this HCM cohort, QTc and S wave anomalies in V4 lead were found to be significant and strong predictors of the risk of appropriate ICD therapy. Patients with QTc ≥464 ms and long or deep S wave had the highest risk. After QTc interval and V4-S wave anomalies adding to the HCM-risk-SCD model, the prediction effect is significantly improved.
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http://dx.doi.org/10.3389/fcvm.2022.882662DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9133535PMC
May 2022

miR-188-3p targets skeletal endothelium coupling of angiogenesis and osteogenesis during ageing.

Cell Death Dis 2022 May 25;13(5):494. Epub 2022 May 25.

Department of Endocrinology, Endocrinology Research Center, Xiangya Hospital of Central South University, Changsha, 410008, Hunan, China.

A specific bone capillary subtype, namely type H vessels, with high expression of CD31 and endomucin, was shown to couple angiogenesis and osteogenesis recently. The number of type H vessels in bone tissue declines with age, and the underlying mechanism for this reduction is unclear. Here, we report that microRNA-188-3p (miR-188-3p) involves this process. miRNA-188-3p expression is upregulated in skeletal endothelium and negatively regulates the formation of type H vessels during ageing. Mice with depletion of miR-188 showed an alleviated age-related decline in type H vessels. In contrast, endothelial-specific overexpression of miR-188-3p reduced the number of type H vessels, leading to decreased bone mass and delayed bone regeneration. Mechanistically, we found that miR-188 inhibits type H vessel formation by directly targeting integrin β3 in endothelial cells. Our findings indicate that miR-188-3p is a key regulator of type H vessel formation and may be a potential therapeutic target for preventing bone loss and accelerating bone regeneration.
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http://dx.doi.org/10.1038/s41419-022-04902-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9130327PMC
May 2022

Triclosan is the Predominant Antibacterial Compound in Ontario Sewage Sludge.

Environ Sci Technol 2022 May 20. Epub 2022 May 20.

Department of Chemistry, University of Toronto, Toronto, ON M5S 3H6, Canada.

Sewage treatment plants (STPs) accumulate both antibiotic and nonantibiotic antimicrobial compounds that can select for antibiotic resistant bacteria. Herein, we aimed to identify the predominant antibacterial compounds impacting from Ontario sewage sludge consisting of thousands of unknown compounds. Among the 10 extracted sludge samples, 6 extracts exerted significant growth inhibition effects in . A total of 103 compounds were tentatively detected across the 10 sludge samples by suspect screening, among which the bacterial enoyl-ACP reductase (FabI) inhibitor triclocarban was detected at the highest abundance. A hypomorphic FabI knockdown strain was highly susceptible to the sludge extracts, confirming FabI inhibitors as the primary antibacterial compounds in the sludge. Protein affinity pulldown identified triclosan as the major ligand binding to a His-tagged FabI protein from the sludge, despite the higher abundance of triclocarban in the same samples. Effect-directed analysis was used to determine the contributions of triclosan to the observed antibacterial potencies. Antibacterial effects were only detected in F and F across 20 fractions, which was consistent with the elution of triclosan and triclocarban in the same two fractions. Further, potency mass balance analysis confirmed that triclosan explained the majority (58-113%) of inhibition effects from sludge extracts. This study highlighted triclosan as the predominant antibacterial compound in sewage sludge impacting despite the co-occurrence of numerous other antibiotics and nonantibiotics.
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http://dx.doi.org/10.1021/acs.est.2c00406DOI Listing
May 2022

Sofosbuvir and ledipasvir decreased nephrotic syndrome caused by IgA nephropathy with a membranoproliferative pattern of injury in hepatitis C virus-induced cirrhosis: a case report.

Ann Transl Med 2022 Apr;10(8):494

Department of Nephrology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Background: Immunoglobulin (Ig) A nephropathy (IgAN) with a membranoproliferative pattern of injury that manifests as nephrotic syndrome (NS) is rarely reported in hepatitis C virus (HCV)-induced cirrhosis. It is not known whether eradication of HCV by direct-acting antiviral (DAA) drugs can lead to remission of proteinuria and improve the long-term prognosis.

Case Description: We report the case of a 52-year-old woman with HCV cirrhosis for 10 years. She had undergone splenectomy and cholecystectomy due to complications of liver cirrhosis. The patient presented with NS and was diagnosed by kidney biopsy with IgAN with a membranoproliferative pattern of injury. Twelve-week sofosbuvir and ledipasvir therapy successfully eradicated HCV in this decompensated cirrhosis patient and resulted in partial remission of IgAN. The patient stayed in partial remission for 4 years and had her first relapse with deterioration of portal hypertension and suspected hepatic carcinoma despite a sustained HCV virologic response. We consider the IgAN in this case to be secondary to liver cirrhosis and HCV infection rather than a primary nephropathy. DAA drugs which have no direct reno-protective effect resulted in partial remission of IgAN because they eradicated HCV and improved the liver disorder.

Conclusions: Although relapse of IgAN could occur when liver cirrhosis deteriorates, DAA treatment may be considered an alternative for similar patients.
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http://dx.doi.org/10.21037/atm-21-5289DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9096367PMC
April 2022

DNA methylation in polycystic ovary syndrome: Emerging evidence and challenges.

Reprod Toxicol 2022 08 10;111:11-19. Epub 2022 May 10.

Faculty of Nursing, Guangxi University of Chinese Medicine, Nanning 530200, Guangxi, China. Electronic address:

Polycystic ovary syndrome (PCOS) is a disease related to reproductive endocrine abnormalities in women of reproductive age, often accompanied by metabolic diseases such as hyperandrogenemia, insulin resistance and dyslipidemia. However, the etiology and mechanism of PCOS are still unclear. In recent years, more and more studies have found that epigenetic factors play an important role in PCOS. DNA methylation is the most widely studied epigenetic modification. At present, changes of DNA methylation have been found in serum, ovarian, hypothalamus, skeletal muscle, adipose tissue of PCOS patients, and these changes are closely related to insulin resistance, lipid metabolism and follicular development of PCOS. Although the current research on DNA methylation in PCOS is not in-depth, it indicated up a good direction for future research on the etiology and mechanism of PCOS. This review discussed the relationship between DNA methylation and PCOS. It is expected to help accelerate the application of DNA methylation in the diagnosis and treatment of PCOS.
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http://dx.doi.org/10.1016/j.reprotox.2022.04.010DOI Listing
August 2022

Utility of the DHFR-based destabilizing domain across mouse models of retinal degeneration and aging.

iScience 2022 May 6;25(5):104206. Epub 2022 Apr 6.

Department of Ophthalmology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390, USA.

The dihydrofolate reductase (DHFR) destabilizing domain (DD) serves as a promising approach to conditionally regulate protein abundance in a variety of tissues. To test whether this approach could be effectively applied to a wide variety of aged and disease-related ocular mouse models, we evaluated the DHFR DD system in the eyes of aged mice (up to 24 months), a light-induced retinal degeneration (LIRD) model, and two genetic models of retinal degeneration ( and mice). The DHFR DD was effectively degraded in all model systems, including mice, which showed significant defects in chymotrypsin proteasomal activity. Moreover, trimethoprim (TMP) administration stabilized the DHFR DD in all mouse models. Thus, the DHFR DD-based approach allows for control of protein abundance in a variety of mouse models, laying the foundation to use this strategy for the conditional control of gene therapies to potentially treat multiple eye diseases.
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http://dx.doi.org/10.1016/j.isci.2022.104206DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9062244PMC
May 2022
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