Publications by authors named "Bo Hu"

1,622 Publications

  • Page 1 of 1

Gray and white matter abnormality in patients with T2DM-related cognitive dysfunction: a systemic review and meta-analysis.

Nutr Diabetes 2022 Aug 15;12(1):39. Epub 2022 Aug 15.

Department of Radiology, Functional and Molecular Imaging Key Lab of Shaanxi Province, Tangdu Hospital, Fourth Military Medical University (Air Force Medical University), 569 Xinsi Road, Xi'an, 710038, Shaanxi, China.

Aims/hypothesis: Brain structure abnormality in patients with type 2 diabetes mellitus (T2DM)-related cognitive dysfunction (T2DM-CD) has been reported for decades in magnetic resonance imaging (MRI) studies. However, the reliable results were still unclear. This study aimed to make a systemic review and meta-analysis to find the significant and consistent gray matter (GM) and white matter (WM) alterations in patients with T2DM-CD by comparing with the healthy controls (HCs).

Methods: Published studies were systemically searched from PubMed, MEDLINE, Cochrane Library and Web of Science databases updated to November 14, 2021. Studies reporting abnormal GM or WM between patients with T2DM-CD and HCs were selected, and their significant peak coordinates (x, y, z) and effect sizes (z-score or t-value) were extracted to perform a voxel-based meta-analysis by anisotropic effect size-signed differential mapping (AES-SDM) 5.15 software.

Results: Total 15 studies and 16 datasets (1550 participants) from 7531 results were involved in this study. Compared to HCs, patients with T2DM-CD showed significant and consistent decreased GM in right superior frontal gyrus, medial orbital (PFCventmed. R, BA 11), left superior temporal gyrus (STG. L, BA 48), and right calcarine fissure / surrounding cortex (CAL. R, BA 17), as well as decreased fractional anisotropy (FA) in right inferior network, inferior fronto-occipital fasciculus (IFOF. R), right inferior network, longitudinal fasciculus (ILF. R), and undefined area (32, -60, -42) of cerebellum. Meta-regression showed the positive relationship between decreased GM in PFCventmed.R and MoCA score, the positive relationship between decreased GM in STG.L and BMI, as well as the positive relationship between the decreased FA in IFOF.R and age or BMI.

Conclusions/interpretation: T2DM impairs the cognitive function by affecting the specific brain structures. GM atrophy in PFCventmed. R (BA 11), STG. L (BA 48), and CAL. R (BA 17), as well as WM injury in IFOF. R, ILF. R, and undefined area (32, -60, -42) of cerebellum. And those brain regions may be valuable targets for future researches. Age, BMI, and MoCA score have a potential influence on the altered GM or WM in T2DM-CD.
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http://dx.doi.org/10.1038/s41387-022-00214-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9378704PMC
August 2022

Mesoscale Finite Element Modeling of Mortar under Sulfate Attack.

Materials (Basel) 2022 Aug 8;15(15). Epub 2022 Aug 8.

Key Laboratory of Roads and Railway Engineering Safety Control, Ministry of Education, Shijiazhuang Tiedao University, Shijiazhuang 050013, China.

In this paper, a 2D mesoscale finite element (FE) numerical model of mortar, considering the influence of the ITZ, was proposed to evaluate the corrosion of mortar in sodium sulfate. On the mesoscale, the corroded mortar was regarded as a three-phase composite material composed of sand, cement paste, and an interface transition zone (ITZ). Firstly, the volume fractions and mechanical parameters (elastic modulus, Poisson's ratio, and strength) of the mesoscale phases were obtained. Then, the cement paste and the ITZ were combined to form an equivalent matrix by homogenization methods, and the calibrated constitutive relations of the equivalent matrix were established. Subsequently, a two-dimensional (2D) random circular aggregate (RCA) model and a 2D random polygonal aggregate (RPA) model of corroded mortar were established using the random aggregate model. The failure process of corroded mortar specimens under uniaxial compression was simulated by the mesoscale FE numerical model. Comparing the simulation results with the measured stress-strain curves of the uniaxial compression test, it was found that the simulation results of the 2D RP model were closer to the experimental results than those of the 2D RC model. Meanwhile, the numerical simulation results were in good agreement with the experimental results, and the error values of peak stress between the simulation results and the measured results were within 7%, which showed that the 2D mesoscale FE model could accurately predict the results of a uniaxial compression test of a mortar specimen under sulfate attack.
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http://dx.doi.org/10.3390/ma15155452DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9369817PMC
August 2022

Clinical Characteristics and Transplant-Free Survival Across the Spectrum of Pulmonary Vascular Disease.

J Am Coll Cardiol 2022 Aug;80(7):697-718

Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.

Background: PVDOMICS (Pulmonary Vascular Disease Phenomics) is a precision medicine initiative to characterize pulmonary vascular disease (PVD) using deep phenotyping. PVDOMICS tests the hypothesis that integration of clinical metrics with omic measures will enhance understanding of PVD and facilitate an updated PVD classification.

Objectives: The purpose of this study was to describe clinical characteristics and transplant-free survival in the PVDOMICS cohort.

Methods: Subjects with World Symposium Pulmonary Hypertension (WSPH) group 1-5 PH, disease comparators with similar underlying diseases and mild or no PH and healthy control subjects enrolled in a cross-sectional study. PH groups, comparators were compared using standard statistical tests including log-rank tests for comparing time to transplant or death.

Results: A total of 1,193 subjects were included. Multiple WSPH groups were identified in 38.9% of PH subjects. Nocturnal desaturation was more frequently observed in groups 1, 3, and 4 PH vs comparators. A total of 50.2% of group 1 PH subjects had ground glass opacities on chest computed tomography. Diffusing capacity for carbon monoxide was significantly lower in groups 1-3 PH than their respective comparators. Right atrial volume index was higher in WSPH groups 1-4 than comparators. A total of 110 participants had a mean pulmonary artery pressure of 21-24 mm Hg. Transplant-free survival was poorest in group 3 PH.

Conclusions: PVDOMICS enrolled subjects across the spectrum of PVD, including mild and mixed etiology PH. Novel findings include low diffusing capacity for carbon monoxide and enlarged right atrial volume index as shared features of groups 1-3 and 1-4 PH, respectively; unexpected, frequent presence of ground glass opacities on computed tomography; and sleep alterations in group 1 PH, and poorest survival in group 3 PH. PVDOMICS will facilitate a new understanding of PVD and refine the current PVD classification. (Pulmonary Vascular Disease Phenomics Program PVDOMICS [PVDOMICS]; NCT02980887).
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http://dx.doi.org/10.1016/j.jacc.2022.05.038DOI Listing
August 2022

Proof of concept for developing novel feeds for cattle from wasted food and crop biomass to enhance agri-food system efficiency.

Sci Rep 2022 Aug 10;12(1):13630. Epub 2022 Aug 10.

Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, 382 W. Street Rd., Kennett Square, PA, 19348, USA.

Modern agri-food systems generate large amounts of crop-based biomass that are unfit for direct human consumption but potentially suitable for livestock feeding in production of meats, milk, and eggs. This study aims to develop novel feeds for cattle from some of those biomass materials through the natural microbial-driven processes of ensiling. Fruit and vegetables resembling supermarket discards were ensiled alone or co-ensiled with corn crop residues, mushroom wastes, etc. via laboratory experiments. Longitudinal sample analyses showed that (co-)ensiling was successful, with pH and fermentation acids changing rapidly into desirable ranges (pH < 4.5, the acids 5-13% DM with lactic acid dominating). The (co-)ensiled products had key nutritional parameters comparable to those of good quality forages commonly used on dairy farms. Additionally, in vitro incubation experiments indicated that the ensiled products could substitute certain conventional feeds while maintaining diet digestibility. Findings from this pilot study provide a proof of principle that quality novel feeds for cattle can be generated by co-ensiling food discards and low-value crop residues. Future research and animal feeding trials to demonstrate the utility of this approach can help societies more effectively utilize untapped biomass resources, strengthening the regenerative capacity of agri-food systems towards a more sustainable food future.
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http://dx.doi.org/10.1038/s41598-022-17812-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9365796PMC
August 2022

Experimental study on compression mechanical characteristics of filled rock joints after multiple pre-impacts.

Sci Rep 2022 Aug 10;12(1):13628. Epub 2022 Aug 10.

School of Civil Engineering, Chang'an University, Xi'an, 710064, China.

The prefabricated artificial filled jointed rock specimens are impacted by a self-made drop hammer impact device for many times, and the specimens with different degrees of cumulative damage characteristics are obtained. Then, the static and dynamic compression mechanical properties are studied by using universal testing machine and SHPB device. Through the static compression test, the strength and deformation characteristics of jointed rock specimens after multiple impacts are obtained, and the influence of the damage degree of jointed rock specimens characterized by wave velocity on the compressive strength of filled joints is analysed. Based on the results of SHPB impact test, the dynamic strength and deformation evolution, wave propagation law and energy dissipation law of filled joints after multiple impacts are analysed. During the SHPB test, the impact failure process of rock specimens is recorded by a high-speed camera. The experimental results show that the damage degree of jointed rock samples increases nonlinearly after multiple impacts. The attenuation laws of static strength and dynamic strength of rock samples under the same damage evolution conditions are different. With the increase of impact times, the failure mode of jointed rock samples after damage is simpler and tends to compression failure.
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http://dx.doi.org/10.1038/s41598-022-15849-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9365792PMC
August 2022

Advances in the development of biodegradable coronary stents: A translational perspective.

Mater Today Bio 2022 Dec 19;16:100368. Epub 2022 Jul 19.

Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.

Implantation of cardiovascular stents is an important therapeutic method to treat coronary artery diseases. Bare-metal and drug-eluting stents show promising clinical outcomes, however, their permanent presence may create complications. In recent years, numerous preclinical and clinical trials have evaluated the properties of bioresorbable stents, including polymer and magnesium-based stents. Three-dimensional (3D) printed-shape-memory polymeric materials enable the self-deployment of stents and provide a novel approach for individualized treatment. Novel bioresorbable metallic stents such as iron- and zinc-based stents have also been investigated and refined. However, the development of novel bioresorbable stents accompanied by clinical translation remains time-consuming and challenging. This review comprehensively summarizes the development of bioresorbable stents based on their preclinical/clinical trials and highlights translational research as well as novel technologies for stents (e.g., bioresorbable electronic stents integrated with biosensors). These findings are expected to inspire the design of novel stents and optimization approaches to improve the efficacy of treatments for cardiovascular diseases.
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http://dx.doi.org/10.1016/j.mtbio.2022.100368DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9352968PMC
December 2022

Uncovering the Heterogeneity and Clinical Relevance of Circulating Tumor-Initiating Cells in Hepatocellular Carcinoma Using an Integrated Immunomagnetic-Microfluidic Platform.

ACS Appl Mater Interfaces 2022 Aug 2;14(32):36425-36437. Epub 2022 Aug 2.

Department of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, 180 Fenglin Road, Shanghai 200032, P. R. China.

Circulating tumor-initiating cells (CTICs) with stem cell-like properties play pivotal roles in tumor metastasis and recurrence. However, little is known about the biology and clinical relevance of CTICs in hepatocellular carcinoma (HCC). Here, we investigated the molecular heterogeneity and clinical relevance of CTICs in HCC using a novel integrated immunomagnetic-microfluidic platform (iMAC). We constructed the iMAC and evaluated its ability to detect CTICs using a series of spiked cell experiments. A four-channel microfluidic chip was applied to investigate the composition of CTICs in patients with primary and recurrent HCC utilizing microbeads labeled with one of four stem-related markers: epithelial cell adhesion molecule (EpCAM), CD133, CD90, and CD24. The dynamic changes of these four CTIC subsets were serially monitored during treatment courses. Finally, single-cell RNA profiling was used to reveal the molecular characteristics of the four CTIC subsets. The iMAC platform detected significantly more EpCAM CTICs in the blood samples from 33 HCC patients than the FDA-approved CellSearch system (0.92 ± 0.94 0.23 ± 0.36, < 0.001). The number of EpCAM CTICs (≥0.75/mL) detected by iMAC was a predictor of early recurrence ( = 0.007). The distinct stem-related markers' expression of CTICs could distinguish primary HCC, recurrent HCC, and TACE-resistant HCC. Single-cell transcriptional profiling proved the heterogeneity among individual CTICs and separated the four CTIC subsets into distinct phenotypes. Dissecting the heterogeneity of CTICs using the iMAC represents a novel and informative method for accurate CTIC detection and characterization. This innovative technology will enable more indepth cancer biology research and clinical cancer management than is currently available.
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http://dx.doi.org/10.1021/acsami.2c09085DOI Listing
August 2022

Prediction of Neurological Deterioration After Intracerebral Hemorrhage: The SIGNALS Score.

J Am Heart Assoc 2022 Aug 2;11(15):e026379. Epub 2022 Aug 2.

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

Background Intracerebral hemorrhage is the most disabling and lethal form of stroke. We aimed to develop a novel clinical score for neurological deterioration during hospitalization after intracerebral hemorrhage. Methods and Results We analyzed data from the CHERRY (Chinese Cerebral Hemorrhage: Mechanism and Intervention) study. Two-thirds of eligible patients were randomly allocated into the training cohort (n=1027) and one-third into the validation cohort (n=515). Multivariable logistic regression was used to identify factors associated with neurological deterioration (an increase in National Institutes of Health Stroke Scale of ≥4 or death) within 15 days after symptom onset. A prediction score was developed based on regression coefficients derived from the logistic model. The site, size, gender, National Institutes of Health Stroke Scale, age, leukocyte, sugar (SIGNALS) score was developed as a sum of individual points (0-8) based on site (1 point for infratentorial location), size (3 points for >20 mL of supratentorial hematoma volume or 2 points for >10 mL of infratentorial hematoma volume), sex (1 point for male sex), National Institutes of Health Stroke Scale score (1 point for >10), age (1 point for ≥70 years), white blood cell (1 point for>9.0×10/L), and fasting blood glucose (1 point>7.0 mmol/L). The proportion of patients who suffered from neurological deterioration increased with higher SIGNALS score, showing good discrimination and good calibration in the training cohort (C statistic, 0.821; Hosmer-Lemeshow test, =0.687) and in the validation cohort (C statistic, 0.848; Hosmer-Lemeshow test, =0.592), respectively. Conclusions The SIGNALS score reliably predicts the risk of in-hospital neurological deterioration of patients with intracerebral hemorrhage.
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http://dx.doi.org/10.1161/JAHA.122.026379DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9375508PMC
August 2022

Hypersensitivity of Zebrafish htr2b Mutant Embryos to Sertraline Indicates a Role for Serotonin Signaling in Cardiac Development.

J Cardiovasc Pharmacol 2022 08 1;80(2):261-269. Epub 2022 Aug 1.

Departments of Pediatrics.

Abstract: Selective serotonin reuptake inhibitors (SSRIs) are antidepressants prescribed in 10% of pregnancies in the United States. Maternal use of SSRIs has been linked to an elevated rate of congenital heart defects, but the exact mechanism of pathogenesis is unknown. Previously, we have shown a decrease in cardiomyocyte proliferation, left ventricle size, and reduced cardiac expression of the serotonin receptor 5-HT 2B in offspring of mice exposed to the SSRI sertraline during pregnancy, relative to offspring of untreated mice. These results suggest that disruption of serotonin signaling leads to heart defects. Supporting this conclusion, we show here that zebrafish embryos exposed to sertraline develop with a smaller ventricle, reduced cardiomyocyte number, and lower cardiac expression of htr2b relative to untreated embryos. Moreover, zebrafish embryos homozygous for a nonsense mutation of htr2b ( htr2bsa16649 ) were sensitized to sertraline treatment relative to wild-type embryos. Specifically, the ventricle area was reduced in the homozygous htr2b mutants treated with sertraline compared with wild-type embryos treated with sertraline and homozygous htr2b mutants treated with vehicle control. Whereas long-term effects on left ventricle shortening fraction and stroke volume were observed by echocardiography in adult mice exposed to sertraline in utero, echocardiograms of adult zebrafish exposed to sertraline as embryos were normal. These results implicate the 5-HT 2B receptor functions in heart development and suggest zebrafish are a relevant animal model that can be used to investigate the connection between maternal SSRI use and elevated risk of congenital heart defects.
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http://dx.doi.org/10.1097/FJC.0000000000001297DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9354722PMC
August 2022

Galcanezumab in episodic migraine: the phase 3, randomized, double-blind, placebo-controlled PERSIST study.

J Headache Pain 2022 Jul 28;23(1):90. Epub 2022 Jul 28.

Department of Neurology, Chinese PLA General Hospital, Beijing, China.

Background: Galcanezumab, a humanized monoclonal antibody that binds calcitonin gene-related peptide, has demonstrated efficacy and good tolerability in patients with episodic migraine in previous phase 3 trials. We report results from the PERSIST study, which was designed to assess the efficacy and safety of galcanezumab in patients with episodic migraine from China, India, and Russia.

Methods: This phase 3 study was conducted at 40 centers in China (n = 26), India (n = 10), and Russia (n = 4). Eligible adult patients with episodic migraine were randomized in a 1:1 ratio to receive monthly galcanezumab 120 mg (with 240 mg loading dose) or placebo during a double-blind, 3-month treatment period. The primary endpoint was the overall mean change from baseline in monthly migraine headache days (MHDs). Key secondary endpoints were the mean proportion of patients with ≥ 50%, ≥ 75%, and 100% reductions from baseline in MHDs and mean change in the Migraine-Specific Quality of Life Questionnaire (MSQ) Role Function-Restrictive domain score.

Results: In total, 520 patients were randomized and received at least one dose of galcanezumab (N = 261) or placebo (N = 259). The least squares (LS) mean reduction from baseline in monthly MHDs over 3 months was significantly greater with galcanezumab compared with placebo (-3.81 days vs. -1.99 days; p < 0.0001). Significantly greater mean proportions of patients with galcanezumab versus placebo had ≥ 50%, ≥ 75%, and 100% reductions from baseline in MHDs (all p < 0.0001). The overall mean improvement from baseline in MSQ Role Function-Restrictive score over 3 months was significantly greater with galcanezumab versus placebo (p < 0.0001). There were no clinically meaningful differences between the galcanezumab and placebo group on any safety parameters except for a higher incidence of injection site pruritus (5.0% vs. 0.0%), injection site reaction (3.8% vs. 0.4%), and injection site discomfort (2.3% vs. 0.0%). TEAEs related to injection sites were mild in severity, except in 1 patient who had a moderate injection site reaction. Six serious adverse events were reported by 6 patients (2 galcanezumab, 4 placebo).

Conclusions: Galcanezumab 120 mg once monthly was effective and well tolerated in patients with episodic migraine from China, India, and Russia.

Trial Registration: ClinicalTrials.gov Identifier NCT03963232 (PERSIST), registered May 24, 2019.
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http://dx.doi.org/10.1186/s10194-022-01458-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9330971PMC
July 2022

Comparative Transcriptome Analysis Provides Novel Insights into the Effect of Lipid Metabolism on Laying of Geese.

Animals (Basel) 2022 Jul 11;12(14). Epub 2022 Jul 11.

Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China.

The lower egg production of geese (20~60 eggs per year) compared with chicken and duck limits the development of the industry, while the yolk weight and fatty liver susceptibility of geese was higher than that of other poultry. Therefore, the relationship between lipid metabolism and the laying performance of geese remains to be explored. Phenotypically, we observed that the liver fat content of the high-, low-, and no-egg production groups decreased in turn, while the abdominal fat weight increased in turn. For transcriptional regulation, the KEGG pathways related to lipid metabolism were enriched in all pairwise comparisons of abdominal fat and liver through functional analysis. However, some KEGG pathways related to inflammation and the circadian rhythm pathway were enriched by DEGs only in abdominal fat and the liver, respectively. The DEGs in ovarian stroma among different groups enriched some KEGG pathways related to ovarian steroidogenesis and cell adhesion. Our research reveals that lipid metabolism regulated by the circadian rhythm of the liver may directly or indirectly affect ovarian function through the inflammation and hormone secretion of abdominal fat. These results offer new insights into the regulation mechanisms of goose reproductive traits.
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http://dx.doi.org/10.3390/ani12141775DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9311715PMC
July 2022

Synthesis of 4-Tetrazolyl-Substituted 3,4-Dihydroquinazoline Derivatives with Anticancer Activity via a One-Pot Sequential Ugi-Azide/Palladium-Catalyzed Azide-Isocyanide Cross-Coupling/Cyclization Reaction.

J Org Chem 2022 Aug 26;87(15):9488-9496. Epub 2022 Jul 26.

School of Pharmacy, Xianning Medical College, Hubei University of Science and Technology, Xianning 437100, Hubei, P. R. China.

A new one-pot preparation of 4-tetrazolyl-3,4-dihydroquinazolines has been reported. The Ugi-azide reactions of 2-azidobenzaldehydes, amines, trimethylsilyl azide, and isocyanides produced azide intermediates without separation, which were treated with isocyanides to give 4-tetrazolyl-3,4-dihydroquinazoline derivatives through a sequential Palladium-catalyzed azide-isocyanide cross-coupling/cyclization reaction in moderate to good yields. The biological evaluation demonstrated that compound inhibited breast cancer cells well and displayed broad applications for synthesis and medicinal chemistry.
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http://dx.doi.org/10.1021/acs.joc.2c00382DOI Listing
August 2022

N6-Methyladenosine-induced miR-143-3p promotes intervertebral disc degeneration by regulating SOX5.

Bone 2022 Jul 23;163:116503. Epub 2022 Jul 23.

Key Laboratory of Non-Coding RNA Transformation Research of Anhui Higher Education Institution, No. 2 Zheshan West Road, Wuhu 241001, Anhui, China. Electronic address:

Intervertebral disc degeneration is the basic cause of lumbocrural pain, which not only causes pain and but also serious economic burdens on patients. Increasingly more evidence has shown that tumor necrosis factor-α (TNF-α) is involved in the pathological process of intervertebral disc degeneration, but the specific molecular mechanism is still unclear. This study investigated the potential mechanism and function of methyltransferase-like 3 (METTL3)/miR-143-3p/SOX5 regulatory axis in nucleus pulposus cells under the action of TNF-α. Human nucleus pulposus cells were treated with TNF-α to construct an in vitro model of intervertebral disc degeneration. Flow cytometry, quantitative reverse-transcription PCR (RT-qPCR), Western blot (WB) and luciferase assays were used to identify the mechanism of action of miR-143-3p in the course of intervertebral disc degeneration in vitro and the downstream targeted regulatory molecules. The role of miR-143-3p in intervertebral disc degeneration was also validated by in vivo. RT-qPCR, WB, coimmunoprecipitation (Co-IP) and flow cytometry were used to verify the regulatory effect of METTL3 on miR-143-3p maturation. RT-qPCR and WB were adopted to detect differences in METTL3, miR-143-3p and SOX5 expression in human nucleus pulposus tissue. miR-143-3p in nucleus pulposus cells was involved in the regulation of extracellular matrix metabolism and apoptosis after TNF-α stimulation, and intervertebral disc degeneration was relieved by effectively regulating miR-143-3p expression. Subsequent experiments showed that the downstream direct target gene of miR-143-3p was SOX5 and that miR-143-3p negatively regulated the expression of SOX5. In addition, METTL3 promoted miR-143-3p maturation, and METTL3 and miR-143-3p were significantly upregulated in degenerative nucleus pulposus, an effect that was significantly negatively correlated with low SOX5 expression. In conclusion, TNF-α upregulates METTL3, METTL3 promotes miR-143-3p maturation, and miR-143-3p inhibits the transcriptional activity of SOX5 through targeted binding, thereby inducing intervertebral disc degeneration. The inhibition of METTL3 or miR-143-3p expression may be an effective way to treat intervertebral disc degeneration.
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http://dx.doi.org/10.1016/j.bone.2022.116503DOI Listing
July 2022

Projections of dependency and associated social care expenditure for the older population in England to 2038: effect of varying disability progression.

Age Ageing 2022 Jul;51(7)

Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne, UK.

Objectives: to assess the effect of recent stalling of life expectancy and various scenarios for disability progression on projections of social care expenditure between 2018 and 2038, and the likelihood of reaching the Ageing Society Grand Challenge mission of five extra healthy, independent years at birth.

Design: two linked projections models: the Population Ageing and Care Simulation (PACSim) model and the Care Policy and Evaluation Centre long-term care projections model, updated to include 2018-based population projections.

Population: PACSim: about 303,589 individuals aged 35 years and over (a 1% random sample of the England population in 2014) created from three nationally representative longitudinal ageing studies.

Main Outcome Measures: Total social care expenditure (public and private) for older people, and men and women's independent life expectancy at age 65 (IndLE65) under five scenarios of changing disability progression and recovery with and without lower life expectancy.

Results: between 2018 and 2038, total care expenditure was projected to increase by 94.1%-1.25% of GDP; men's IndLE65 increasing by 14.7% (range 11.3-16.5%), exceeding the 8% equivalent of the increase in five healthy, independent years at birth, although women's IndLE65 increased by only 4.7% (range 3.2-5.8%). A 10% reduction in disability progression and increase in recovery resulted in the lowest increase in total care expenditure and increases in both men's and women's IndLE65 exceeding 8%.

Conclusions: interventions that slow down disability progression, and improve recovery, could significantly reduce social care expenditure and meet government targets for increases in healthy, independent years.
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http://dx.doi.org/10.1093/ageing/afac158DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9308990PMC
July 2022

Immobilization of chromium enhanced by arbuscular mycorrhizal fungi in semi-aquatic habitats with biochar addition.

J Hazard Mater 2022 Jul 8;439:129562. Epub 2022 Jul 8.

Department of Applied Ecology, Faculty of Environmental Sciences, Czech University of Life Sciences Prague, Kamýcká 129, Praha-Suchdol 16500, Czech Republic.

Arbuscular mycorrhizal fungi (AMF) exhibit great potential in heavy-metal immobilization in semi-aquatic habitats. Under high heavy-metal stress, however, the role of AMF is limited, and the detoxification mechanism of AMF in heavy metals' stabilization remains unclear. This study investigated the effects of AMF on a wetland plant (Iris pseudacorus) and chromium (Cr) immobilization at different water depths in semi-aquatic habitats with biochar addition. Results showed that AMF increased the physiological and photosynthetic functions in I. pseudacorus under Cr exposures. Besides, AMF alleviated the accumulation of reactive oxygen species and lipid peroxidation by enhancing the antioxidant enzyme activities. AMF and biochar significantly decreased Cr concentrations in outlet water and increased Cr accumulation in I. pseudacorus. Besides, biochar also vastly improved Cr accumulation in the substrate under the fluctuating water depth. AMF reduced Cr bioavailability in the substrate, with Cr (Ⅵ) concentrations and acid-soluble forms of Cr decreased by 0.3-64.5% and 19.0-40.8%, respectively. Micro-proton-induced X-ray emission was used to determine element localization and revealed that AMF improved the nutrients uptake by wetland plants and inhibited Cr translocation from roots to shoots. Overall, this study demonstrated that the interaction between AMF and biochar could significantly enhance the immobilization of high Cr concentrations in semi-aquatic habitats.
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http://dx.doi.org/10.1016/j.jhazmat.2022.129562DOI Listing
July 2022

Distribution characteristics of microplastics in the soil of mangrove restoration wetland and the effects of microplastics on soil characteristics.

Ecotoxicology 2022 Jul 21. Epub 2022 Jul 21.

Department of Environmental Science and Engineering, College of Chemical Engineering, Huaqiao University, Xiamen, Fujian, 361021, China.

The dense vegetation in the wetland could effectively retain microplastic particles, and the distribution of microplastics varied significantly under different planting densities. In addition, microplastics in the soil environment can affect soil properties to a certain extent, which in turn can affect soil functions and biodiversity. In this study, we investigated the distribution of soil microplastics in a mangrove restoration wetland under different planting densities and their effects on wetland soil properties. The results indicated that the average abundance of soil microplastics was 2177.5 n/500 g, of which 70.9% exhibited a diameter ranging from 0.038-0.05 mm, while the remaining soil microplastics accounted for less than 20% of all microplastics, indicating that smaller-diameter microplastics were more likely to accumulate in wetland soil. The microplastic abundance could be ranked based on the planting density as follows: 0.5 × 0.5 m > 1.0 × 0.5 m > 1.0 × 1.0 m > control area. Raman spectroscopy revealed that the predominant microplastic categories in this region included polyethylene terephthalate (PET, 52%), polyethylene (PE, 24%) and polypropylene (PP, 15%). Scanning electron microscopy (SEM) images revealed fractures and tears on the surface of microplastics. EDS energy spectra indicated a large amount of metal elements on the surface of microplastics. Due to the adsorptive features of PET, this substance could influence the soil particle size distribution and thus the soil structure. All physicochemical factors, except for the soil pH, were significantly affected by PET. In addition, the CV analysis results indicated that soils in vegetated areas are more susceptible to PET than are soils in bare ground areas, leading to greater variation in their properties.
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http://dx.doi.org/10.1007/s10646-022-02561-3DOI Listing
July 2022

Origin and function of activated fibroblast states during zebrafish heart regeneration.

Nat Genet 2022 Aug 21;54(8):1227-1237. Epub 2022 Jul 21.

Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin Institute for Medical Systems Biology, Berlin, Germany.

The adult zebrafish heart has a high capacity for regeneration following injury. However, the composition of the regenerative niche has remained largely elusive. Here, we dissected the diversity of activated cell states in the regenerating zebrafish heart based on single-cell transcriptomics and spatiotemporal analysis. We observed the emergence of several transient cell states with fibroblast characteristics following injury, and we outlined the proregenerative function of collagen-12-expressing fibroblasts. To understand the cascade of events leading to heart regeneration, we determined the origin of these cell states by high-throughput lineage tracing. We found that activated fibroblasts were derived from two separate sources: the epicardium and the endocardium. Mechanistically, we determined Wnt signalling as a regulator of the endocardial fibroblast response. In summary, our work identifies specialized activated fibroblast cell states that contribute to heart regeneration, thereby opening up possible approaches to modulating the regenerative capacity of the vertebrate heart.
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http://dx.doi.org/10.1038/s41588-022-01129-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7613248PMC
August 2022

Prediction of Neurological Deterioration After Intracerebral Hemorrhage: The SIGNALS Score.

J Am Heart Assoc 2022 Jul 20:e026379. Epub 2022 Jul 20.

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

Background Intracerebral hemorrhage is the most disabling and lethal form of stroke. We aimed to develop a novel clinical score for neurological deterioration during hospitalization after intracerebral hemorrhage. Methods and Results We analyzed data from the CHERRY (Chinese Cerebral Hemorrhage: Mechanism and Intervention) study. Two-thirds of eligible patients were randomly allocated into the training cohort (n=1027) and one-third into the validation cohort (n=515). Multivariable logistic regression was used to identify factors associated with neurological deterioration (an increase in National Institutes of Health Stroke Scale of ≥4 or death) within 15 days after symptom onset. A prediction score was developed based on regression coefficients derived from the logistic model. The site, size, gender, National Institutes of Health Stroke Scale, age, leukocyte, sugar (SIGNALS) score was developed as a sum of individual points (0-8) based on site (1 point for infratentorial location), size (3 points for >20 mL of supratentorial hematoma volume or 2 points for >10 mL of infratentorial hematoma volume), sex (1 point for male sex), National Institutes of Health Stroke Scale score (1 point for >10), age (1 point for ≥70 years), white blood cell (1 point for>9.0×10/L), and fasting blood glucose (1 point>7.0 mmol/L). The proportion of patients who suffered from neurological deterioration increased with higher SIGNALS score, showing good discrimination and good calibration in the training cohort (C statistic, 0.821; Hosmer-Lemeshow test, =0.687) and in the validation cohort (C statistic, 0.848; Hosmer-Lemeshow test, =0.592), respectively. Conclusions The SIGNALS score reliably predicts the risk of in-hospital neurological deterioration of patients with intracerebral hemorrhage.
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http://dx.doi.org/10.1161/JAHA.121.026379DOI Listing
July 2022

Reconstruction of Tumor-Induced Pelvic Defects With Customized, Three-Dimensional Printed Prostheses.

Front Oncol 2022 30;12:935059. Epub 2022 Jun 30.

Department of Orthopedics, The First Affiliated Hospital of Anhui Medical University, Hefei, China.

Background: Reconstruction of pelvis girdle stability after tumor-induced hemipelvectomy remains challenging. We surgically treated 13 patients with custom-made, three-dimensional printed hemipelvic prostheses. We aim to identify the preliminary outcomes for patients who have been managed with more mixed regions of prosthetic pelvic reconstruction and the feasibility of two reconstructive systems.

Methods: Seven male patients and 6 female patients treated at our center between January 2019 and May 2021 were included. There were 11 primary sarcomas and 2 solitary bone metastases. After en bloc tumor resection, two types of personalized, three-dimensional printed prostheses were fixed to restore the stability and rebuild the load transfer. The position of the reconstructed hemipelvis was evaluated on an anteroposterior plain radiograph. The complications and outcomes were traced. One amputation specimen was discovered through histological analysis of the porous structure.

Results: The operative duration was 467 ± 144 min, and the blood loss was 3,119 ± 662 ml. During a follow-up of 22.4 ± 8.5 months, two patients had delayed wound healing and one had a second-stage flap transfer. One patient with osteosarcoma died of pulmonary metastasis 27 months after surgery. Two patients with marginal resection suffered from local recurrence and had extra surgeries. One patient had traumatic hip dislocation 2 months after surgery and manipulative reduction was performed. The acetabular inclination of the affected side was 42.2 ± 4.3°, compared with 42.1 ± 3.9° on the contralateral side. The horizontal distance between the center of the femoral head and the middle vertical line was 10.4 ± 0.6 cm, while the reconstructed side was 9.8 ± 0.8 cm. No significant difference in acetabular position after surgery was found ( > 0.05). The amputation specimen harvested from one patient with local recurrence demonstrated bone and soft tissue ingrowth within the three-dimensional printed trabecular structure. Walking ability was preserved in all patients who are still alive and no prosthesis-related complications occurred. The MSTS score was 22.0 ± 3.7.

Conclusions: Both types of custom-made, three-dimensional printed prostheses manifested excellent precision, mechanical stability, and promising functional rehabilitation. The porous structure exhibited favorable histocompatibility to facilitate the ingrowth of bone and soft tissue.
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http://dx.doi.org/10.3389/fonc.2022.935059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9282862PMC
June 2022

C698R mutation in Lrsam1 gene impairs nerve regeneration in a CMT2P mouse model.

Sci Rep 2022 Jul 16;12(1):12160. Epub 2022 Jul 16.

Department of Neurology, Wayne State University School of Medicine, Detroit, MI, USA.

Missense mutation C694R in the RING domain of the LRSAM1 gene results in a dominantly inherited polyneuropathy, Charcot-Marie-Tooth disease type 2P (CMT2P). We have generated and characterized a Lrsam1 knock-in mouse model produced through CRISPR/Cas9 technology. Both heterozygous (Lrsam1) and homozygous (Lrsam1) knock-in mice exhibited normal motor functions on behavioral tests as well as normal on nerve conduction studies. Axonal density and myelin thickness were not significantly different between mutants and wild-type mice by sciatic nerve morphometric analysis up to 17 months of age. In line with these normal findings, protein-protein interactions between mutant LRSAM1 and RNA-binding proteins (such as FUS and G3BP1) were still present in mouse cells, which differs from the disrupted interactions between these proteins in human CMT2P cells. However, after crush nerve injury, Lrsam1 mice had a mild, but statistically significant, reduced compound nerve action potential and conduction velocity during recovery. Therefore, C698R mutation results in a mild impaired nerve regeneration in mice. We speculate that repetitive nerve injuries may, at least partially, contribute to the slowly progressive axonal loss in CMT2P.
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http://dx.doi.org/10.1038/s41598-022-15902-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9288509PMC
July 2022

Explainable Machine-Learning Model for Prediction of In-Hospital Mortality in Septic Patients Requiring Intensive Care Unit Readmission.

Infect Dis Ther 2022 Aug 14;11(4):1695-1713. Epub 2022 Jul 14.

Department of Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, 430071, Hubei, China.

Introduction: Septic patients requiring intensive care unit (ICU) readmission are at high risk of mortality, but research focusing on the association of ICU readmission due to sepsis and mortality is limited. The aim of this study was to develop and validate a machine learning (ML) model for predicting in-hospital mortality in septic patients readmitted to the ICU using routinely available clinical data.

Methods: The data used in this study were obtained from the Medical Information Mart for Intensive Care (MIMIC-IV, v1.0) database, between 2008 and 2019. The study cohort included patients with sepsis requiring ICU readmission. The data were randomly split into a training (75%) data set and a validation (25%) data set. Nine popular ML models were developed to predict mortality in septic patients readmitted to the ICU. The model with the best accuracy and area under the curve (A.C.) in the validation cohort was defined as the optimal model and was selected for further prediction studies. The SHAPELY Additive explanations (SHAP) values and Local Interpretable Model-Agnostic Explanation (LIME) methods were used to improve the interpretability of the optimal model.

Results: A total of 1117 septic patients who had required ICU readmission during the study period were enrolled in the study. Of these participants, 434 (38.9%) were female, and the median (interquartile range [IQR]) age was 68.6 (58.4-79.2) years. The median (IQR) ICU interval duration was 2.60 (0.64-5.78) days. After feature selection, 31 of 47 clinical factors were ultimately chosen for use in model construction. Of the nine ML models tested, the best performance was achieved with the random forest (RF) model, with an A.C. of 0.81, an accuracy of 85% and a precision of 62% in the validation cohort. The SHAP summary analysis revealed that Glasgow Coma Scale score, urine output, blood urea nitrogen, lactate, platelet count and systolic blood pressure were the top six most important factors contributing to the RF model. Additionally, the LIME method demonstrated how the RF model works in terms of explaining risk of death prediction in septic patients requiring ICU readmission.

Conclusion: The ML models reported here showed a good prognostic prediction ability in septic patients requiring ICU readmission. Of the features selected, the parameters related to organ perfusion made the largest contribution to outcome prediction during ICU readmission in septic patients.
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http://dx.doi.org/10.1007/s40121-022-00671-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9282631PMC
August 2022

Comparison of flash-free and conventional bonding systems: A systematic review and meta-analysis.

Angle Orthod 2022 Jul 14. Epub 2022 Jul 14.

Objectives: To review the literature systematically to compare the performance of adhesive precoated flash-free bonding systems with conventional adhesive precoated (APC) and operator-coated (OPC) bonding systems.

Materials And Methods: PubMed, Cochrane Library, Web of Science, and Embase were searched for potential eligible studies. Study selection and data collection were conducted independently. Statistical analysis was performed by Review Manager 5.3. The Cochran Q test was used to test heterogeneity in the included studies. Risk of bias was evaluated using Cochrane RoB 2.0 tool for randomized controlled trials.

Results: Six studies were included and the overall risk-of-bias judgment was low risk of bias to some concerns. The results of the meta-analyses showed that flash-free required significantly less bonding time than APC (mean difference [MD]: -1.56; 95% confidence intervals [CIs]: -2.56 to -0.56), and no significant differences were found in bond failure rates (risk ratio [RR]: 1.54; 95% Cis: 0.27 to 8.89) and adhesive remnant index (ARI) (MD: -0.50; 95% CIs: -1.14 to 0.14) between them. Qualitative analysis showed that flash-free might have a positive effect on enamel demineralization compared to APC but the quantity of plaque did not differ between them.

Conclusions: The flash-free bonding system significantly reduced bonding time and it had comparable bond failure rates with APC. So far, there is not enough evidence to support its positive effect on reducing enamel demineralization and the pathogenic bacteria around brackets. In summary, flash-free might be a better choice for clinical bracket bonding.
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http://dx.doi.org/10.2319/122221-932.1DOI Listing
July 2022

Hyjapones A-D, trimethylated acyphloroglucinol meroterpenoids from Hypericum japonicum thunb. With anti-inflammatory activity.

Phytochemistry 2022 Jul 9;202:113308. Epub 2022 Jul 9.

School of Pharmacy, Anhui Medical University, Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Medical University, Hefei, 230032, People's Republic of China. Electronic address:

Four undescribed trimethylated acylphloroglucinol meroterpenoids, hyjapones A-D, along with seven known analogues, were isolated from Hypericum japonicum Thunb. Hyjapone A represents the first example of a double norflavesones-caryophyllene hybrid featuring a rare 6/6/9/4/6/6 hexacyclic frame. Hyjapone D was isolated as a natural product for the first time. Their structures and absolute configurations were established by comprehensive spectroscopic data analyses and electronic circular dichroism (ECD) calculations. The anti-inflammatory activities of all compounds were evaluated using lipopolysaccharide-induced RAW264.7 cells. Hyperjapone A showed more pronounced anti-inflammatory effect through reducing the production of nitric oxide (IC value of 11.32 ± 2.10 μM) and proinflammatory cytokines. In addition, the mechanistic studies revealed hyperjapone A inhibited LPS-induced activation of nuclear factor-κB.
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http://dx.doi.org/10.1016/j.phytochem.2022.113308DOI Listing
July 2022

Recursive Decomposition Network for Deformable Image Registration.

IEEE J Biomed Health Inform 2022 Jul 11;PP. Epub 2022 Jul 11.

Deformation decomposition serves as a good solution for deformable image registration when the deformation is large. Current deformation decomposition methods can be categorized into cascade-based methods and pyramid-based methods. However, cascade-based methods suffer from heavy computational burdens and long inference time due to their structures of repeated subnetworks, while the effectiveness of pyramid-based methods is constrained by their limited numbers of resolution levels. In this paper, to address both the insufficient and inefficient decomposition problems in current deformation decomposition methods, we propose a recursive decomposition network (RDN) to offer a novel solution for deformable image registration. Stage-wise recursion can efficiently decompose a large deformation into different pyramid estimation stages without using repeated subnetworks like in cascade-based methods. Level-wise recursion can sufficiently decompose the deformation inside each resolution level instead of only one-time estimation like in pyramid-based methods. Extensive experiments and ablation studies on two representative datasets validate the effectiveness and efficiency of our proposed RDN.
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http://dx.doi.org/10.1109/JBHI.2022.3189696DOI Listing
July 2022

"Advancing" Advance Care Planning to Veterans in the Veterans Health Administration.

Mil Med 2022 Jul 8. Epub 2022 Jul 8.

Department of Psychiatry, University of Arkansas for Medical Sciences, College of Medicine, Little Rock, AR 72205, USA.

Introduction: The completion rate of Advance Directive (ADs) in the Veterans Health Administration (VHA) is unknown. There is substantial literature on the need for effective Advance Care Planning (ACP) that leads to an AD to ensure that health care preferences for patients are known. Advance Directive are essential to consider since ACP, which explains and plans Advance Directive, does not reach all individuals. Health inequities, such as those experienced in rural areas, continue to exist. While ACP may disproportionately affect rural-residing veterans and their providers, a VHA program was specifically designed to increase ACP engagement with rural veterans and to address several systemic barriers to ACP.

Materials And Methods: This descriptive analysis seeks to identify patient, provider, and geographic characteristics associated with higher rates of ACP participation in VHA. An observational examination of the profile of veterans and the types of ACP (e.g., individual or in groups) using administrative data for all beneficiaries receiving VHA health care services in federal fiscal year (FY) 2020 was conducted as part of a national program evaluation. The measures include patient-level data on demographics (e.g., race, ethnicity, gender), unique patient identifiers (e.g., name, social security number), geographic characteristics of patient's location (e.g., rurality defined as Rural-Urban Commuting Areas [RUCA]), VHA priority group; provider-level data (e.g., type of document definition, clinic stop codes, visit date used to verify Advance Care Planning via Group Visits [ACP-GV] attendance; data not shown), and electronic health record note titles that indicated the presence of ACP in VHA (e.g., "Advance Directive [AD] Discussion" note title, "ACP-GV CHAR 4 code"). Pearson's chi-square statistics were used for between-group comparisons based on a two-sided test with a significance level of 0.05.

Results: The overall rate of AD discussions among unique VHA users in FY2020 was 5.2% (95% CI: 5.2%-5.2%) and for Advance Care Planning via Group Visits, which targets rural veterans using groups, it was 1.8% (95% CI: 1.8%-1.9%). Advance Directive discussions in VHA are more successful at reaching middle age (M = 64; SD = 16), African Americans, males, veterans living in urban areas, and veterans with a VA disability (Priority Group 1-4). Advance Care Planning delivered in groups is reaching slightly younger veterans under the age of 75 years (M = 62; SD = 15), African Americans, females, disabled veterans (e.g., Priority Group 1-4), and more veterans residing in rural communities compared to the national population of VHA users.

Conclusion: Advance Directive discussion rates are low across VHA, yet intentional efforts with ACP via group visits are reaching veterans who are considered underserved owing to residing in rural areas. Advance Care Planning needs to be a well-informed clinical priority for VHA to engage with the entire veteran population and to support the completion of ADs.
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http://dx.doi.org/10.1093/milmed/usac196DOI Listing
July 2022

Unconventional Protein Secretion in Brain Tumors Biology: Enlightening the Mechanisms for Tumor Survival and Progression.

Front Cell Dev Biol 2022 15;10:907423. Epub 2022 Jun 15.

Laboratory of Neurobiology and Stem Cells, Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.

Non-canonical secretion pathways, collectively known as unconventional protein secretion (UPS), are alternative secretory mechanisms usually associated with stress-inducing conditions. UPS allows proteins that lack a signal peptide to be secreted, avoiding the conventional endoplasmic reticulum-Golgi complex secretory pathway. Molecules that generally rely on the canonical pathway to be secreted may also use the Golgi bypass, one of the unconventional routes, to reach the extracellular space. UPS studies have been increasingly growing in the literature, including its implication in the biology of several diseases. Intercellular communication between brain tumor cells and the tumor microenvironment is orchestrated by various molecules, including canonical and non-canonical secreted proteins that modulate tumor growth, proliferation, and invasion. Adult brain tumors such as gliomas, which are aggressive and fatal cancers with a dismal prognosis, could exploit UPS mechanisms to communicate with their microenvironment. Herein, we provide functional insights into the UPS machinery in the context of tumor biology, with a particular focus on the secreted proteins by alternative routes as key regulators in the maintenance of brain tumors.
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http://dx.doi.org/10.3389/fcell.2022.907423DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9242006PMC
June 2022

Engineering the β-Oxidation Pathway in for the Production of -10, -12-Conjugated Linoleic Acid.

J Agric Food Chem 2022 Jul 28;70(27):8377-8384. Epub 2022 Jun 28.

School of Chemical Engineering, Xuzhou College of Industrial Technology, No. 1 Xiangwang Road, Xuzhou, Jiangsu 221140, P. R. China.

-10, -12-Conjugated linoleic acid (10, 12-CLA) is an octadecadienoic acid with various biological benefits. Previously, linoleic acid isomerase from (PAI) was overexpressed in () to produce 10, 12-CLA. However, the 10, 12-CLA yield was restricted by the peroxisomal β-oxidation pathway. In this study, to minimize the degradation of 10, 12-CLA, four genetically modified strains of ( and ) were constructed and compared in terms of production stability and yield of 10, 12-CLA using safflower seed oil as substrates. The strain exhibited the best results, as revealed by the reduction of the 10, 12-CLA degradation rate from 58.5 to 18.6 mg/L/h. Additionally, the YLUpex10mP recombinant strain bearing six copies of o combined with deletion enhanced 10, 12-CLA production to 7.4 g/L and exhibited a CLA degradation rate of 19.7 mg/L/h, a 78% decrease from that of the control strain. Finally, in a bioreactor containing low-cost volatile fatty acids as partial carbon sources, the 10, 12-CLA content in the YLUpex10mP strain increased to 9.7 g/L, 1.3 times higher than in flasks. To our knowledge, this is the highest 10, 12-CLA yield through microbial synthesis reported to date.
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http://dx.doi.org/10.1021/acs.jafc.2c02242DOI Listing
July 2022

Immune suppressive function of IL-1α release in the tumor microenvironment regulated by calpain 1.

Oncoimmunology 2022 15;11(1):2088467. Epub 2022 Jun 15.

Immunology Translational Research Programme, Department of Microbiology of Immunology, Yong Loo Lin School of Medicine, Immunology Programme, Life Sciences Institute, National University of Singapore, Singapore, Singapore.

Interleukin-1α (IL-1α) plays an important role in inflammation and hematopoiesis. Many tumors have increased IL-1α expression. However, the immune regulatory role of secreted IL-1α in tumor development and whether it can be targeted for cancer therapy are still unclear. Here, we found that tumoral-secreted IL-1α significantly promoted hepatocellular carcinoma (HCC) development . Tumoral-released IL-1α were found to inhibit T and NK cell activation, and the killing capacity of CD8 T cells. Moreover, MDSCs were dramatically increased by tumoral-released IL-1α in both spleens and tumors. Indeed, higher tumoral IL-1α expression is associated with increased tumoral infiltration of MDSCs in HCC patients. Further studies showed that tumoral-released IL-1α promoted MDSC recruitment to the tumor microenvironment through a CXCR2-dependent mechanism. Depletion of MDSCs could diminish the tumor-promoting effect of tumoral-released IL-1α. On the contrary, systemic administration of recombinant IL-1α protein significantly inhibited tumor development by activating T cells. In fact, IL-1α protein could promote T cell activation and enhance the cytotoxicity of CD8 T cells . Thus, our study demonstrated that tumoral-released IL-1α promoted tumor development through recruiting MDSCs to inhibit T cell activation, while systemic IL-1α directly promoted anti-tumor T cell responses. We further identified calpain 1 as the major intracellular protease mediating tumoral IL-1α secretion. Calpain 1 KO tumors had diminished IL-1α release and reduced tumor development. Thus, our findings provide new insights into the functions of secreted IL-1α in tumor immunity and its implications for immunotherapy.
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http://dx.doi.org/10.1080/2162402X.2022.2088467DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9225674PMC
June 2022

A Comprehensive Analysis of HAVCR1 as a Prognostic and Diagnostic Marker for Pan-Cancer.

Front Genet 2022 8;13:904114. Epub 2022 Jun 8.

Department of Laboratory Medicine, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Hepatitis A virus cellular receptor (HAVCR1) is a type-1 integral membrane glycoprotein that plays a key role in immunity and renal regeneration and is abnormally expressed in various tumor types. Nonetheless, the function of HAVCR1 in pan-cancer remains unknown. In this study, we comprehensively analyzed the expression and promoter methylation level of HAVCR1 and assessed the immune cell infiltration, correlation between stromal and immune cell admixture, CD (Cluster of Differentiation) and HAVCR1 expression and prognostic value of HAVCR1 mRNA expression in Liver hepatocellular carcinoma (LIHC) and Pancreatic adenocarcinoma (PAAD). Our results showed that HAVCR1 was overexpressed while the promoter methylation of HAVCR1 was decreased in Liver hepatocellular carcinoma and Pancreatic adenocarcinoma. HAVCR1 was associated with increased infiltration of B cells, CD8 cells, macrophages, neutrophils and Dendritic cells in Liver hepatocellular carcinoma and Pancreatic adenocarcinoma. HAVCR1 expression was positively correlated with the immune, stromal and estimate scores of Pancreatic adenocarcinoma and the stromal and estimate scores of Liver hepatocellular carcinoma. Furthermore, HAVCR1 expression was correlated with other immune molecules such as HHLA2 (Human endogenous retrovirus-H long terminal repeat-associating protein 2), CD44 and TNFRSF4 (TNF Receptor Superfamily Member 4) in Liver hepatocellular carcinoma and Pancreatic adenocarcinoma. During Kaplan-Meier analysis, high HAVCR1 expression in Liver hepatocellular carcinoma and Pancreatic adenocarcinoma correlated with poor survival. A marginally significant -value ( = 0.051) was obtained when the relationship between HAVCR1 expression in Liver hepatocellular carcinoma and prognosis was analyzed, attributed to the small sample size. Overall, we provided compelling evidence that HAVCR1 could be a prognostic and diagnostic marker for Liver hepatocellular carcinoma and Pancreatic adenocarcinoma.
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http://dx.doi.org/10.3389/fgene.2022.904114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9213751PMC
June 2022

Transcriptomics-based analysis of co-exposure of cadmium (Cd) and 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) indicates mitochondrial dysfunction induces NLRP3 inflammasome and inflammatory cell death in renal tubular epithelial cells.

Ecotoxicol Environ Saf 2022 Aug 23;241:113790. Epub 2022 Jun 23.

Forensic and Pathology Laboratory, Department of Public Health, Department of Pathology, Institute of Forensic Science, Jiaxing University, Jiaxing 314001, Zhejiang, China. Electronic address:

Environmental pollution often releases multiple contaminants resulting in as yet largely uncharacterized additive toxicities. Cadmium (Cd) is a widespread pollutant that induces nephrotoxicity in animal models and humans. However, the combined effect of Cd in causing nephrotoxicity with 2,2',4,4'-tetrabromodiphenyl ether (BDE-47), a typical congener of polybrominated diphenyl ethers (PBDEs), has not been evaluated and mechanisms are not completely clear. Here, we applied transcriptome sequencing analysis to investigate the combined toxicity of Cd and BDE-47 in the renal tubular epithelial cell lines HKCs. Cd or BDE-47 exposure decreased cell viability in a dose-dependent manner, and exhibited cell swelling and rounding similar to necrosis, which was exacerbated by co-exposure. Transcriptomic analysis revealed 2191, 1331 and 3787 differentially-expressed genes following treatment with Cd, BDE-47 and co-exposure, respectively. Interestingly, functional annotation and enrichment analyses showed involvement of pathways for oxidative stress, NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome and inflammatory cell death for all three treatments. Examination of indices of mitochondrial function and oxidative stress in HKC cells showed that the levels of reactive oxygen species (ROS), malondialdehyde (MDA) and intracellular calcium ion concentration [Ca]i were elevated, while superoxide dismutase (SOD) and mitochondrial membrane potential (MMP) were decreased. The ratio of apoptotic and necrotic cells and intracellular lactate dehydrogenase (LDH) release were increased by Cd or BDE-47 exposure, and was aggravated by co-exposure, and was attenuated by ROS scavenger N-Acetyl-L-cysteine (NAC). NLRP3 inflammasome and pyroptosis pathway-related genes of NLRP3, adaptor molecule apoptosis-associated speck-like protein (ASC), caspase-1, interleukin-18 (IL-18) and IL-1β were elevated, while gasdermin D (GSDMD) was down-regulated, and protein levels of NLRP3, cleaved caspase-1 and cleaved GSDMD were increased, most of which were relieved by NAC. Our data demonstrate that exposure to Cd and BDE-47 induces mitochondrial dysfunction and triggers NLRP3 inflammasome and GSDMD-dependent pyroptosis leading to nephrotoxicity, and co-exposure exacerbates this effect, which could be attenuated by inhibiting ROS. This study provides a further mechanistic understanding of kidney damage, and co-exposure impact is worthy of concern and should be considered to improve the accuracy of environmental health assessment.
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http://dx.doi.org/10.1016/j.ecoenv.2022.113790DOI Listing
August 2022
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