Publications by authors named "Jing Hu"

1,551 Publications

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plays critical roles in host health.

Crit Rev Microbiol 2022 May 21:1-19. Epub 2022 May 21.

State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, China.

, an intestinal microorganism, belongs to , one of the most abundant microorganisms in the mammalian gut. It is a mucin-degrading bacterium that can colonise intestines of mammals such as humans and mice by utilising mucin as the only nitrogen and carbon source. When colonises the intestine, its metabolites interact with the intestinal barrier, affecting host health by consolidating the intestinal barrier, regulating metabolic functions of the intestinal and circulatory systems, and regulating immune functions. This review summarised the mechanisms of -host interactions that are relevant to host health. We focussed on characteristics of in relation to its metabolites to provide a comprehensive understanding of and its effects on host health and disease processes.
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http://dx.doi.org/10.1080/1040841X.2022.2037506DOI Listing
May 2022

Programmed cell death process in freshwater Microcystis aeruginosa and marine Phaeocystis globosa induced by a plant derived allelochemical.

Sci Total Environ 2022 May 19:156055. Epub 2022 May 19.

Zhejiang University, Ocean College, 1 Zheda Road, Zhoushan, Zhejiang 316000, China; Key Laboratory of Watershed Non-point Source Pollution Control and Water Eco-security of Ministry of Water Resources, College of Environmental and Resources Sciences, Zhejiang University, Hangzhou 310058, China. Electronic address:

Harmful algal blooms (HAB) are a serious problem worldwide. Allelochemicals from natural plants were recently thought to be promising anti-algaecide in controlling harmful algae. However, the programmed cell death (PCD) process of algae under allelopathic pressure induced by 5,4'-dihydroxyflavone (5,4'-DHF) was poorly understood. In this study, two common and worldwide distributed microalgae, Microcystis aeruginosa and Phaeocystis globosa were selected as target algae, and the PCD processes induced by 5,4'-DHF were cross-compared between the two species. Both algae species were inhibited significantly by 5,4'-DHF with the relative sensitivity of 0.11. To uncover the PCD progress systematically, signals for PCD triggering, antioxidant enzyme activity, photosynthetic ability variation, caspase-like activities and typical indicators were investigated. In both species, typical indicators of PCD - phosphatidylserine externalization and chromatin condensation - were detected. The intracellular reactive oxygen species (ROS), nitric oxide (NO) and HO were the potential signal molecules to stimulate PCD, and caspase-like activities were activated with an elevation of cytochrome c indicating the initiation of PCD in both species. However, P. globosa responded to 5,4'-DHF immediately after 3 h with the elevation of ROS and not in M. aeruginosa. Antioxidant enzyme activities of superoxide dismutase (SOD) and catalase (CAT) in M. aeruginosa and P. globosa also showed different patterns on day 3. Specifically, SOD activity in M. aeruginosa increased significantly while it decreased significantly in P. globosa, CAT activity in M. aeruginosa decreased significantly while it increased significantly in P. globosa (p < 0.05). Malondialdehyde (MDA) content in P. globosa increased significantly (p < 0.001) while it showed no variation in M. aeruginosa. Overall, this study is one of the earliest studies to explore the inhibition and action mechanism of plant derived flavonoids on harmful algae from the perspective of PCD, and provide new insights into the antialgal mechanism of allelochemicals.
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http://dx.doi.org/10.1016/j.scitotenv.2022.156055DOI Listing
May 2022

Algal bloom forecasting with time-frequency analysis: A hybrid deep learning approach.

Water Res 2022 May 14;219:118591. Epub 2022 May 14.

Ocean College, Zhejiang University, #1 Zheda Road, Zhoushan, Zhejiang 316021, China; Key Laboratory of Watershed Non-point Source Pollution Control and Water Eco-security of Ministry of Water Resources, College of Environmental and Resources Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, China. Electronic address:

The rapid emergence of deep learning long-short-term-memory (LSTM) technique presents a promising solution to algal bloom forecasting. However, the discontinuous and non-stationary processes within algal dynamics still largely limit the functions of LSTMs. To overcome this challenge, an advanced time-frequency wavelet analysis (WA) technique was introduced to enhance the prediction accuracy of LSTMs. Herein, the novel hybrid approach (named WLSTM) successfully decreased the algal forecasting inaccuracy of classic LSTMs by 41% ± 8% in Lake Mendota (Wisconsin, USA), with powerful one-step-ahead predictions at hourly, daily, and monthly time resolutions (R = 0.976, 0.878, and 0.814, respectively). In addition, the WLSTM outperformed the other two widely used algal forecasting approaches - deep neural network (DNN), and autoregressive-integrated-moving-average (ARIMA) model, represented by average 72% and 85% decrease in root-mean-square-error, respectively. Furthermore, the WLSTM was implemented in an experimentally fertilized lake (Lake Tuesday, Michigan) for a multi-step forecasting examination. It satisfactorily forecasted the algal fluctuations involving substantial peak and extreme values (average R > 0.900) and presented accurate judgment outcomes to their bloom levels with high accuracy > 95% on average. This work highlighted the utility of deep learning approaches in effective early-warning for algal blooms, and demonstrated an important direction for improving the adaptability of conventional deep learning approaches to the aquatic problems.
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http://dx.doi.org/10.1016/j.watres.2022.118591DOI Listing
May 2022

[Identification of c.196C>T nonsense RUNX2 variant in a Chinese patient with cleidocranial dysplasia].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2022 May;39(5):526-529

Department of Endocrinology, National Health Commission Key Laboratory of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.

Objective: To detect the genetic variant of a child with cleidocranial dysplasia (CCD) and to find out the causation of the illness.

Methods: Gene variant was identified by the second generation targeted sequencing and Sanger sequencing.

Results: The gene sequencing revealed that the RUNX2 gene had c.196C>T(p.Glu66*) nonsense variant, which was predicted to be a pathogenic variant according to the ACMG guidelines(PVS1+PS2).

Conclusion: The variant of c.196C > T in the RUNX2 gene may be the cause of the child with CCD, and the novel variant enriches the RUNX2 gene variant spectrum.
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http://dx.doi.org/10.3760/cma.j.cn511374-20210119-00055DOI Listing
May 2022

Heavy metal and nutrient concentrations in top- and sub-soils of greenhouses and arable fields in East China - Effects of cultivation years, management, and shelter.

Environ Pollut 2022 May 18:119494. Epub 2022 May 18.

Institute for Meteorology and Climate Research, Atmospheric Environmental Research (IMK-IFU), Karlsruhe Institute of Technology, Garmisch-Partenkirchen, 82467, Germany; State Key Laboratory of Atmospheric Boundary Layer Physics and Atmospheric Chemistry, Institute of Atmospheric Physics, Chinese Academy of Sciences, Beijing, 100029, China. Electronic address:

Although greenhouse vegetable production in China is rapidly changing, consumers are concerned about food quality and safety. Studies have shown that greenhouse soils are highly eutrophicated and potentially contaminated by heavy metals. However, to date, no regional study has assessed whether greenhouse soils differ significantly in their heavy metal and nutrient loads compared to adjacent arable land. Our study was conducted in Shouguang County, a key region of greenhouse vegetable production in China. Soil samples down to soil depths of 3 m were taken from 60 greenhouse vegetable fields of three different ages (5, 10, and 20 years) and from 20 adjacent arable fields to analyze the concentrations of heavy metals, nutrients, and soil physio-chemical parameters. A comparison of greenhouse soils with adjacent arable fields revealed that for greenhouses, (a) micro (heavy metals: Cu, Zn, and Mn) and macronutrients (Nmin, Olsen-P, available K) were significantly higher by a factor of about five, (b) N:P:K ratios were significantly imbalanced towards P and K, and (c) topsoil (0-30 cm) concentrations of the above-mentioned micro- and macronutrients increased with years of vegetable cultivation. In contrast, the soil concentrations of the heavy metals Cr and Pb were lower in greenhouse soils. Heavy metal concentrations did not vary significantly with soil depth, except for the micronutrients Cu and Zn, which were between 1- and 3-fold higher in the topsoil (0-30 cm) than in the subsoil (30-300 cm). The Nemerow pollution index (P) was 0.37, which was below the recommended environmental threshold value (P < 1). Structural equation model analysis revealed that soil nutrient concentrations in greenhouse soils are directly related to the input of fertilizers and agrochemicals. Lower values of soil Pb and Cr concentrations in greenhouses were due to the sheltering effect of the greenhouse roof, which protected soils from atmospheric deposition due to emissions from nearby industrial complexes.
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http://dx.doi.org/10.1016/j.envpol.2022.119494DOI Listing
May 2022

Short-term exposure to nitrogen dioxide and ischemic stroke incidence in Shenzhen, China: Modification effects by season and temperature.

Ecotoxicol Environ Saf 2022 May 16;239:113644. Epub 2022 May 16.

Department of Environment and Health, Shenzhen Center for Disease Control and Prevention, 8 Longyuan Rd, Shenzhen 518055, Guangdong, China. Electronic address:

Background And Objectives: China has experienced a serious public health burden because of the increased incidence of ischemic stroke. Evidence describing the association between short-term exposure to nitrogen dioxide (NO) and ischemic stroke morbidity is limited, and few studies have focused on the effects of season and temperature. This study aimed to evaluate the acute effects of NO on ischemic stroke incidence in Shenzhen, a southeastern city of China, considering the modified effects of season and temperature.

Methods: A time-stratified case-crossover study was conducted between 2003 and 2014 among 98,482 ischemic stroke hospitalizations. Conditional quasi-Poisson regression was used to estimate the percentage changes in ischemic stroke admissions in relation to each 10 μg/m increment in NO.

Results: NO was positively associated with ischemic stroke onset over the full year, as well as in the cold season (November through April) and on cold days (ambient temperature≤median temperature), with significant single-day effects within 3 days after the exposure, and significant cumulative effects within the delayed five days. The maximum percentage changes were obtained at lag0-5, with 1.81% (95% confidence interval (CI) was 0.86-2.76%) over the full year, 2.75% (1.48-4.03%) in the cold season, and 3.04% (1.74-4.35%) on cold days. Additionally, the effects of exposure were found to be greater in males and people with higher education, and were lasting longer in subgroups of older individuals.

Conclusions: Our findings provide evidence that reductions in NO levels might decrease ischemic stroke morbidity, and enhance the understanding of ischemic stroke occurrence associated with NO modified by season and temperature.
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http://dx.doi.org/10.1016/j.ecoenv.2022.113644DOI Listing
May 2022

Interleukin-38 promotes skin tumorigenesis in an IL-1Rrp2-dependent manner.

EMBO Rep 2022 May 17:e53791. Epub 2022 May 17.

State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, China.

Interleukin-38 (IL-38) is strongly associated with chronic inflammatory diseases; however, its role in tumorigenesis is poorly understood. We demonstrated that expression of IL-38, which exhibits high expression in the skin, is downregulated in human cutaneous squamous cell carcinoma and 7,12-dimethylbenzanthracene/12-O-tetradecanoyl phorbol-13-acetate-induced mouse skin tumorigenesis. IL-38 keratinocyte-specific knockout mice displayed suppressed skin tumor formation and malignant progression. Keratinocyte-specific deletion of IL-38 was associated with reduced expression of inflammatory cytokines, leading to reduced myeloid cell infiltration into the local tumor microenvironment. IL-38 is dispensable for epidermal mutagenesis, but IL-38 keratinocyte-specific deletion reduces proliferative gene expression along with epidermal cell proliferation and hyperplasia. Mechanistically, we first demonstrated that IL-38 activates the c-Jun N-terminal kinase (JNK)/activator protein 1 signal transduction pathway to promote the expression of cancer-related inflammatory cytokines and proliferation and migration of tumor cells in an IL-1 receptor-related protein 2 (IL-1Rrp2)-dependent manner. Our findings highlight the role of IL-38 in the regulation of epidermal cell hyperplasia and pro-tumorigenic microenvironment through IL-1Rrp2/JNK and suggest IL-38/IL-1Rrp2 as a preventive and potential therapeutic target in skin cancer.
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http://dx.doi.org/10.15252/embr.202153791DOI Listing
May 2022

Genetic origin of patients having spastic paraplegia with or without other neurologic manifestations.

BMC Neurol 2022 May 16;22(1):180. Epub 2022 May 16.

Department of Neuromuscular Disease, The Third Affiliated Hospital of Hebei Medical University, 139 Ziqiang Road, Shijiazhuang, Hebei, 050000, PR China.

Background: Hereditary spastic paraplegia (HSP) is a group of neurodegenerative diseases characterized by lower-limb spastic paraplegia with highly genetic and clinical heterogeneity. However, the clinical sign of spastic paraplegia can also be seen in a variety of hereditary neurologic diseases with bilateral corticospinal tract impairment. The purpose of this study is to identify the disease spectrum of spastic paraplegia, and to broaden the coverage of genetic testing and recognize clinical, laboratorial, electrophysiological and radiological characteristics to increase the positive rate of diagnosis.

Methods: Twenty-seven cases were screened out to have definite or suspected pathogenic variants from clinically suspected HSP pedigrees through HSP-associated sequencing and/or expanded genetic testing. One case was performed for enzyme detection of leukodystrophy without next-generation sequencing. In addition, detailed clinical, laboratorial, electrophysiological and radiological characteristics of the 28 patients were presented.

Results: A total of five types of hereditary neurological disorders were identified in 28 patients, including HSP (15/28), leukodystrophy (5/28), hereditary ataxia (2/28), methylmalonic acidemia/methylenetetrahydrofolate reductase deficiency (5/28), and Charcot-Marie-tooth atrophy (1/28). Patients in the HSP group had chronic courses, most of whom were lower limbs spasticity, mainly with axonal neuropathy, and thinning corpus callosum, white matter lesions and cerebellar atrophy in brain MRI. In the non-HSP groups, upper and lower limbs both involvement was more common. Patients with homocysteine remethylation disorders or Krabbe's disease or autosomal recessive spastic ataxia of Charlevoix-Saguenay had diagnostic results in laboratory or imaging examination. A total of 12 new variants were obtained.

Conclusions: HSP had widespread clinical and genetic heterogeneity, and leukodystrophy, hereditary ataxia, Charcot-Marie-Tooth atrophy and homocysteine remethylation disorders accounted for a significant proportion of the proposed HSP. These diseases had different characteristics in clinical, laboratorial, electrophysiological, and radiological aspects, which could help differential diagnosis. Genetic analysis could ultimately provide a clear diagnosis, and broadening the scope of genetic testing could improve the positive rate of diagnosis.
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http://dx.doi.org/10.1186/s12883-022-02708-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9109329PMC
May 2022

Structural Elucidation and genetic identification of the O-antigen from a novel serogroup of Escherichia coli strain 2017LL031.

Carbohydr Res 2022 Apr 29;517:108577. Epub 2022 Apr 29.

Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Lihu Ave. 1800, Wuxi, 214122, China.

The O-antigen is an important virulence factor involved in the survival, virulence and invasion of bacteria. The bacterial serological types are highly dependent on these surface-exposed and structurally unique O-antigen structures. In this work, the structure of O-antigen from an Escherichia coli strain 2017LL031 was elucidated as a hexasaccharide repeating unit: →3)-[β-D-Glcp-(1 → 2)]-α-L-Rhap-(1 → 3)-[α-D-Quip-(1 → 3)-α-D-GlcpA-(1 → 2)]-β-L-Fucp-(1 → 3)-β-D-GlcpNAc-(1→, which is completely different from all known E. coli serogroups. The O-antigen gene cluster (O-AGC) of 2017LL031 was also analyzed and correlates well to its O-Ag. Moreover, the O-AGC of 2017LL031 was deleted and its role in O-Ag biosynthesis was confirmed experimentally. Taken together, our results present that a novel E.coli serotype 2017LL031 is identified.
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http://dx.doi.org/10.1016/j.carres.2022.108577DOI Listing
April 2022

Construction of hypoxia-immune-related prognostic model and targeted therapeutic strategies for cervical cancer.

Int Immunol 2022 May 13. Epub 2022 May 13.

Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, China.

Emerging evidence indicates that hypoxia and immunity play important roles in tumorigenesis and development. However, the hypoxia-immune-related prognostic risk model has not been established in cervical cancer (CC). We aimed to construct a hypoxia-immune-based prognostic risk model with potential application in CC patient prognosis and predicting response to targeted therapy. The RNA-seq data and corresponding clinical information were retrieved from The Cancer Genome Atlas (TCGA) database. Hypoxia and immune status of CC patients were evaluated using the Consensus Clustering method and single sample gene set enrichment analysis (ssGSEA), respectively. The univariate Cox regression, least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression were applied to establish the prognostic risk model of CC. The chemotherapy response for six chemotherapeutic agents of each CC patient was calculated according to the Genomics of Drug Sensitivity in Cancer (GDSC). And the Connectivity Map (CMap) database was performed to screen candidate small molecule drugs. In this study, we identified 7 gene signatures (P4HA2, MSMO1, EGLN1, ZNF316, IKZF3, ISCU, MYO1B) with prognostic values. And the survival time of patients with low-risk was significantly longer than those with high-risk. Meanwhile, CC patients in the high-risk group yielded higher sensitivity to five chemotherapeutic agents. And we listed ten candidate small-molecules drugs that exhibited a high correlation with the prognosis of cervical cancer. Thus, the prognostic model can accurately predict the prognosis of patients with CC and may be helpful for the development of new hypoxia-immune prognostic markers and therapeutic strategies for CC.
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http://dx.doi.org/10.1093/intimm/dxac017DOI Listing
May 2022

Toxicokinetics of zinc oxide nanoparticles and food grade bulk-sized zinc oxide in rats after oral dosages.

NanoImpact 2022 Jan 26;25:100368. Epub 2021 Nov 26.

NHC Key Laboratory of Food Safety Assessment, Chinese Academy of Medical Science Research Unit (2019RU014), China National Center for Food Safety Risk Assessment, Beijing 100021, China. Electronic address:

The increasing application of zinc oxide nanoparticles (ZnO NPs) in consumer products has raised concerns about the potential health risks in human. It is crucial to understand the toxicokinetic information of ZnO NPs, especially the differences between NPs and non-nano form material. This study investigated the toxicokinetic profile of ZnO NPs and food grade bulk-sized ZnO in rats after single or repeated oral dosages. For single oral administration of ZnO suspensions at 350 mg/kgbw, the Zn content in blood and tissues showed no elevation, the majority of ZnO particles were eliminated via feces within 48 h. For repeated oral exposure to ZnO suspensions at 350 mg/kgbw or ZnSO solution at 700 mg/kgbw for 90 days, elevated Zn levels were observed in liver, kidney, and bone in all three treatment groups, the Zn level recovered to normal level in liver and kidney, but not in bone, after a recovery period. ZnO NPs and bulk-sized ZnO showed similarity in toxicokinetics in rats, regardless of exposure duration or gender. ZnO particles shared a similar biodistribution profile with ZnSO, and were likely to be absorbed mostly in ionic forms.
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http://dx.doi.org/10.1016/j.impact.2021.100368DOI Listing
January 2022

Chemical synthesis of a synthetically useful L-galactosaminuronic acid building block.

Chin J Nat Med 2022 May;20(5):387-392

Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, China. Electronic address:

Most bacterial cell surface glycans are structurally unique, and have been considered as ideal target molecules for the developments of detection and diagnosis techniques, as well as vaccines. Chemical synthesis has been a promising approach to prepare well-defined oligosaccharides, facilitating the structure-activity relationship exploration and biomedical applications of bacterial glycans. L-Galactosaminuronic acid is a rare sugar that has been only found in cell surface glycans of gram-negative bacteria. Here, an orthogonally protected L-galactosaminuronic acid building block was designed and chemically synthesized. A synthetic strategy based on glycal addition and TEMPO/BAIB-mediated C6 oxidation served well for the transformation of commercial L-galactose to the corresponding L-galactosaminuronic acid. Notably, the C6 oxidation of the allyl glycoside was more efficient than that of the selenoglycoside. In addition, a balance between the formation of allyl glycoside and the recovery of selenoglycoside was essential to improve efficiency of the NIS/TfOH-catalyzed allylation. This synthetically useful L-galactosaminuronic acid building block will provide a basis for the syntheses of complex bacterial glycans.
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http://dx.doi.org/10.1016/S1875-5364(22)60149-3DOI Listing
May 2022

Microdischarge in Flame as a Source-in-Source for Boosted Excitation of Optical Emission of Chromium.

Anal Chem 2022 May 12. Epub 2022 May 12.

Analytical & Testing Center, Sichuan University, Chengdu, Sichuan 610064, China.

A compact tandem excitation source-in-source was designed by arranging a point discharge (PD) ignited in argon/hydrogen (Ar/H) flame and utilized for boosted excitation for the optical emission of chromium. Through a tungsten coil (W-coil) electrothermal vaporizer (ETV) located right under the tandem source without any interface for sample introduction, a miniaturized optical emission spectrometer was realized. Because the discharge gaseous atmosphere of PD was activated in the flame, the energy consumption of PD for breaking down discharge gas and maintenance of plasma was greatly saved. In addition, the flame could partially atomize or keep the atomized state of analyte atoms through its reducing environment. Therefore, the excitation capability of the tandem source was greatly improved, owing to the synergistic effect of PD microplasma and Ar/H flame. In addition, part of the analyte was atomized/excited on the W-coil, and thereby, dry, pure, and activated analyte species were released from the W-coil and swept into the tandem source for atomization/excitation. Through the collective effect of W-coil ETV, Ar/H flame, and PD microplasma, analytical sensitivity for Cr was greatly enhanced. Under the optimized conditions, with 10 μL sample solution, a limit of detection of 1.5 μg L and a relative standard deviation of 3.6% (20 μg L, = 5) were achieved. Its accuracy was demonstrated by successful analysis of several certified reference materials. Owing to the advantages including high sensitivity, compactness, and cost effectiveness, it is promising to facilitate the miniaturized spectrometer for more elements and potential field analytical chemistry.
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http://dx.doi.org/10.1021/acs.analchem.2c01105DOI Listing
May 2022

Chemical Synthesis and Antigenic Evaluation of Inner Core Oligosaccharides from Acinetobacter baumannii Lipopolysaccharide.

Angew Chem Int Ed Engl 2022 May 11:e202204420. Epub 2022 May 11.

Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China.

Acinetobacter baumannii is currently posing a serious threat to global health. Lipopolysaccharide (LPS) is a potent virulence factor of pathogenic Gram-negative bacteria. To explore the antigenic properties of A. baumannii LPS, four Kdo-containing inner core glycans from A. baumannii strain ATCC 17904 were synthesized. A flexible and divergent method based on the use of the orthogonally substituted α-Kdo-(2→5)-Kdo disaccharides was developed. Selective removal of different protecting groups in these key precursors and elongation of sugar chain via α-stereocontrolled coupling with 5,7-O-di-tert-butylsilylene or 5-O-benzoyl protected Kdo thioglycosides and 2-azido-2-deoxyglucosyl thioglycoside allowed efficient assembly of the target molecules. Glycan microarray analysis of sera from infected patients revealed that the 4,5-branched Kdo trimer was a potential antigenic epitope, which is attractive for further immunological research to develop carbohydrate vaccines against A. baumannii.
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http://dx.doi.org/10.1002/anie.202204420DOI Listing
May 2022

RUVBL1 promotes enzalutamide resistance of prostate tumors through the PLXNA1-CRAF-MAPK pathway.

Oncogene 2022 May 4. Epub 2022 May 4.

The Key Laboratory of Experimental Teratology, Ministry of Education and Department of Pathology, School of Basic Medical Sciences, Shandong University, Jinan, Shandong, 250012, China.

Although enzalutamide improves the overall survival of patients with metastatic prostate cancers, enzalutamide resistance (ENZR) will be inevitably developed. Emerging evidence support that alternative oncogenic pathways may bypass the androgen receptor (AR) signaling to promote ENZR progression, however, the underpinning mechanisms remain poorly defined. Here, we report that the expression of RuvB like AAA ATPase 1 (RUVBL1) is upregulated in ENZR cells and xenograft models and prostate tumors in patients. Enzalutamide increases RUVBL1 accumulation in the cytoplasm, which in turn enhances the recruitment of CRAF proto-oncogene serine/threonine kinase protein to plexin A1 (PLXNA1) and the subsequent activation of the downstream MAPK pathway. Co-overexpression of RUVBL1 and PLXNA1 defines a subgroup of prostate cancer (PCa) patients with a poor prognosis. Furthermore, pharmacological inhibition of RUVBL1 by CB-6644 suppresses ENZR cell proliferation and xenograft growth and allows re-sensitization of ENZR cells and xenografts to enzalutamide, indicating that RUVBL1 may act to substitute the AR signaling to promote cancer cell survival and ENZR development. Together, these findings may lead to the identification of RUVBL1 as a potential therapeutic target for ENZR tumors.
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http://dx.doi.org/10.1038/s41388-022-02332-8DOI Listing
May 2022

Self-Healing and Antibacterial Essential Oil-Loaded Mesoporous Silica/Polyacrylate Hybrid Hydrogel for High-Performance Wearable Body-Strain Sensing.

ACS Appl Mater Interfaces 2022 May 2;14(18):21509-21520. Epub 2022 May 2.

Key Laboratory of Eco-Textile, Ministry of Education, School of Textile Science and Engineering, Jiangnan University, Wuxi 214122, China.

Flexible electronics have aroused great interest over the past few years due to their unique advantages of being wearable and lightweight. Introducing the self-healing function into wearable electronics will contribute to the practical applications of wearable electronics by prolonging the devices' lifetime. In this study, a flexible essential oil (EO)-loaded mesoporous silica ([email protected])/polyacrylate hybrid hydrogel with superb self-healing and antibacterial properties was prepared. The prepared hybrid hydrogel was found to have excellent piezoresistive sensing performance, which could be particularly suitable for human vital activity monitoring. Benefiting from the strong ionic bonding and multiple hydrogen bonds between polyacrylate and [email protected], the hybrid hydrogel could repair its damaged areas with restored sensing and mechanical properties, which suggested excellent self-healing ability. In addition, this hybrid hydrogel, when applied in wearable devices, was found to have high antibacterial ability owing to the slow release of the lemon EO from AMS to kill bacteria. This promising self-healing and antibacterial hybrid hydrogel shows a promising application in wearable electronics for posture monitoring, human-computer interaction, and artificial intelligence.
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http://dx.doi.org/10.1021/acsami.2c03406DOI Listing
May 2022

Appropriateness of Antibiotic Prescriptions in Chinese Primary Health Care and the Impact of the COVID-19 Pandemic: A Typically Descriptive and Longitudinal Database Study in Yinchuan City.

Front Pharmacol 2022 14;13:861782. Epub 2022 Apr 14.

Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China.

The appropriateness of antibiotic prescriptions in primary care has not been well evaluated in China in recent years. Furthermore, the impact of coronavirus disease 2019 (COVID-19) on antibiotic prescriptions has not yet been investigated in China. We aimed to assess the appropriateness of antibiotic prescriptions and to evaluate the potential association between the COVID-19 pandemic and antibiotic prescriptions in primary care settings of Yinchuan, a city in China. This study included 155 primary care institutions and 10,192,713 outpatient visits. Outpatient prescriptions were classified as appropriate, potentially appropriate, inappropriate, or not linked to any diagnosis for antibiotic use following a validated evaluation scheme. Interrupted time-series analyses were performed to assess the effects of the COVID-19 pandemic on antibiotic prescriptions in Chinese primary care facilities. During the study period, 1,287,678 (12.6%, 95% confidence interval [12.6-12.7]) of 10,192,713 outpatient visits in primary care resulted in antibiotic prescriptions. Among 1,287,678 antibiotic prescriptions, 653,335 (50.7% [50.6-50.9]) were inappropriate, 463,081 (36.0% [35.8-36.1]) were potentially appropriate, 171,056 (13.3% [13.1-13.5]) were appropriate, and 206 could not be linked to any diagnosis. Furthermore, patient, physician, and institutional factors were associated with inappropriate antibiotic prescriptions; there was an overall decreasing trend in the proportions of inappropriate antibiotic prescriptions, with the highest level in 2017 (67.1% [66.8-67.5]) and the lowest in 2021 (40.8% [40.3-41.3]). A total of 1,416,120 individual antibiotics were prescribed, of which 1,087,630 (76.8%) were broad-spectrum and 777,672 (54.9%) were classified in the World Health Organization's "Watch" category. In addition, the COVID-19 pandemic was associated with changes of -2.8% (-4.4 to -1.3) in the level and 0.3% (0.2-0.3) in the monthly trend of antibiotic prescription rates, as well as changes of -5.9% (-10.2 to -1.5) in the level and 1.3% (1.0-1.6) in the monthly trend of the proportions of inappropriate antibiotic prescriptions. More than half of the antibiotic prescriptions were inappropriate during the study period in primary care in Yinchuan. The COVID-19 pandemic may be associated with a decrease in the overall and inappropriate use of antibiotics in primary care settings in China.
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http://dx.doi.org/10.3389/fphar.2022.861782DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9049214PMC
April 2022

Facial controlled synthesis of Pt/MnO catalysts with high efficiency for VOCs combustion.

RSC Adv 2021 Apr 4;11(27):16547-16556. Epub 2021 May 4.

Shenzhen University Shenzhen China

Two sets of experiments were initially implemented to explore the best impregnation method and the best morphology substrate. In the first case, Pt/MnO-r-WI catalyst showed a better performance than that of Pt/MnO-r-IW. The test results illustrated that Wetness Impregnation (WI) could enhance the dispersion of Pt, ratios of Mn/Mn, O/O and Pt/Pt as compared to those of Incipient Wetness Impregnation (IW). In the other method, MnO-s catalyst displayed a higher catalytic efficiency than that of MnO-r because the nanosphere morphology had larger BET surface area and pore volume to attract Pt atoms and toluene molecules. Therefore, the Pt/MnO-s-WI catalyst was obtained and showed the best activity with low-temperature redox capability and oxygen mobility. It could eliminate toluene ( ) at a low temperature of 205 °C and remain stable over 150 h. effects of calcination temperature, toluene concentration and gas hourly space velocity (GHSV) were also investigated herein. diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) was also implemented to explore the reaction mechanism. It demonstrated that toluene was firstly adsorbed over Pt on the surface before being oxidized to CO and HO. The whole procedure follows the Mars-van Krevelen mechanism. This work gives a comprehensive understanding of the heterogeneous catalysis mechanism.
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http://dx.doi.org/10.1039/d1ra02112eDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9032203PMC
April 2021

A property-oriented adaptive design framework for rapid discovery of energetic molecules based on small-scale labeled datasets.

RSC Adv 2021 Jul 27;11(41):25764-25776. Epub 2021 Jul 27.

College of Chemistry, Sichuan University Chengdu 610064 People's Republic of China +86 028 8541 2290.

It remains an important challenge to apply machine learning in material discovery with limited-scale datasets available, in particular for the energetic materials. Motivated by the challenge, we developed a Property-oriented Adaptive Design Framework (PADF) to quickly design new energetic compounds with desired properties. The PADF consists of a search space, machine learning model, optimization algorithm and an evaluator based on quantum mechanical calculations. The effectiveness and generality of the PADF were assessed by two case studies on the heat of formation and heat of explosion as the target properties. 88 compounds were selected as the initial training dataset from the search space containing 84 083 compounds generated. SVR.lin/Trade-off coupled with E-state + SOB and KRR/KG coupled with CDS + E-state + SOB were determined to be the best combination pairs for the heat of formation and the heat of explosion, respectively. Most of the ten compounds selected from the first ten iterations exhibit better properties than the optimal sample in the initial dataset. Besides, the heat of explosion as the target property outperforms the heat of formation in designing energetic compounds with high detonation performance. In particular, a new compound selected at the 3rd iteration exhibits high potential as an explosive. Our strategy could be extended to other domains limited by small-scale datasets labeled.
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http://dx.doi.org/10.1039/d1ra03715cDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9037014PMC
July 2021

Preparations for Rheumatoid Arthritis: An Overview of Systematic Reviews.

Evid Based Complement Alternat Med 2022 12;2022:3151936. Epub 2022 Apr 12.

Centre for Evidence-Based Chinese Medicine, Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, China.

Objectives: To summarize the quantity and quality of evidence for using (TwHF) preparations in patients with rheumatoid arthritis (RA) and to find the reasons of the disparity by comprehensively appraising the related systematic reviews (SRs).

Methods: We performed an overview of evidence for the effectiveness and safety of TwHF preparations for patients with RA. We searched seven literature databases from inception to July 15, 2021. We included SRs of TwHF preparations in the treatment of RA. Four tools were used to evaluate the reporting quality, methodological quality, risk of bias, and the certainty of evidence for the included SRs, which are the PRISMA, the AMSTAR-2, the ROBIS, and the GRADE approach.

Results: We included 27 SRs (with 385 studies and 33,888 participants) for this overview. The AMSTAR-2 showed that 19 SRs had critically low methodological quality and the remaining 8 had low methodological quality. The rate of overlaps was 68.31% (263/385), and the CCA (corrected covered area) was 0.53, which indicated the degree of overlap is slight. Based on the assessment of ROBIS, all 27 SRs were rated as low risk in phase 1; one SR was rated as low risk in domain 1, 9 SRs were in low risk in domain 2, 16 SRs were in low risk in domain 3, and 16 SRs were in low risk in domain 4 in phase 2; 7 SRs were rated as low risk in phase 3. Among 27 items of PRISMA, 15 items were reported over 70% of compliance, the reporting quality of 16 SRs was rated as "fair," and 11 were "good." Using GRADE assessment, moderate quality of evidence was found in 5 outcomes, and 5 outcomes were low quality.

Conclusion: The use of TwHF preparations for the treatment of RA may be clinically effective according to the moderate-quality evidence. There are methodological issues, risk of bias, and reporting deficiencies still needed to be improved. SRs with good quality and further randomized clinical trials that focus on clinical important outcomes are needed.
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http://dx.doi.org/10.1155/2022/3151936DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9019410PMC
April 2022

Scalable Preparation and Improved Discharge Properties of [email protected] Cathode Materials for High-Temperature Thermal Battery.

Nanomaterials (Basel) 2022 Apr 15;12(8). Epub 2022 Apr 15.

School of Materials Science and Engineering, Tianjin University, Tianjin 300072, China.

Long-time thermal batteries with high specific energy are crucial for improving the fast response ability of long-range weapons. Due to its high capacity, safety, and stability, the new sulfide cathode has attracted extensive attention. In this study, an [email protected] composite cathode with a core-shell structure was prepared via a combination of hydrothermal and high-temperature vulcanization processes. The novel [email protected] cathode not only delivers a high discharge voltage and output capacity, but also has high thermal stability and excellent conductivity. Benefiting from the synergistic effect of FeS and CoS, the as-synthesized cathode yields a high specific capacity. At a large current density of 1 A/cm, the utilization rate of [email protected] cathode material can reach 72.33%, which is 8.23% higher than that of FeS. Moreover, the maximum output capacity is up to 902 As/g, with a utilization rate of 79.02% at 500 mA/cm. This novel design strategy holds great promise for the development and application of high-performance thermal batteries in the future.
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http://dx.doi.org/10.3390/nano12081360DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9030623PMC
April 2022

3-Indoleacrylic acid from canola straw as a promising antialgal agent - Inhibition effect and mechanism on bloom-forming Prorocentrum donghaiense.

Mar Pollut Bull 2022 May 19;178:113657. Epub 2022 Apr 19.

Department of Marine Science, Ocean College, Zhejiang University, Zhoushan 316021, People's Republic of China. Electronic address:

Harmful algal blooms (HABs) have induced severe damage worldwide. A novel high-efficient antialgal natural chemical, 3-indoleacrylic acid (3-IDC) with a 5-day half-maximal inhibitory concentration (IC), was discovered from canola straw, and its algal inhibition mechanism was investigated. Adverse effects were observed on the growth of P. donghaiense with 3-IDC addition, following an increase in reactive oxygen species (ROS) production. 3-IDC also hindered the photosynthetic mechanism of P. donghaiense cells. Transcriptional results showed 3-IDC inhibiting the functions of all the nutrient assimilating genes, down-regulated ribulose-1,5-bisphosphate carboxylase/oxygenase II, and cytochrome f genes. The expression of heat shock protein (HSP) 70 and 90 and rhodopsin genes were also suppressed. The binding affinity of investigated receptors was observed. The conformational changes induced by the spatial microstructural alteration through 3-IDC may further contribute to the perturbation of those enzyme catalytic activities. The present results provide new insights on controlling HABs using 3-IDC.
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http://dx.doi.org/10.1016/j.marpolbul.2022.113657DOI Listing
May 2022

The homologous region hr4a of Autographa californica multiple nucleopolyhedrovirus specifically enhances viral early promoters.

Virus Res 2022 Jul 16;315:198780. Epub 2022 Apr 16.

College of Life Sciences, Northwest A&F University, Yangling 712100, China. Electronic address:

Autographa californica multiple nucleocapsid polyhedrosis virus (AcMNPV) genome contains several homologous regions (hrs) which can be used as origins of viral DNA replication and transcriptional enhancers. Early studies have found that some hrs can not only stimulate viral early promoters, but also enhance gene expression driven by viral late promoters. In this study, by adding hr4a to the upstream of different types of viral promoters and enhanced green fluorescent protein (egfp) reporter gene, we investigated the enhancement effect of hr4a on eGFP expression. The results showed that hr4a increased the gene transcription controlled by early promoters, but had no enhancer effect on late promoters.
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http://dx.doi.org/10.1016/j.virusres.2022.198780DOI Listing
July 2022

Gene analysis and clinical features of 22 GNE myopathy patients.

Neurol Sci 2022 Apr 19. Epub 2022 Apr 19.

Department of Neuromuscular Disorders, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, People's Republic of China.

Introduction: GNE myopathy is an autosomal recessive distal myopathy caused by a biallelic mutation in UDP-N-acetylglucosamine 2-epomerase/N-acetylmannosamine kinase. In this study, we discuss the clinical features, pathological characteristics, genetic profiles, and atypical clinical manifestations of 22 Chinese GNE patients.

Materials And Methods: Retrospective analysis was performed for GNE myopathy patients at our institute between 2005 and 2021. Histopathological analysis and gene testing were done according to standard protocols.

Results: Molecular analysis revealed 14-reported and 7 novel mutations, including c.125G > A (p.P42Q), c.226G > A (p.V76I), c.970C > G (p.H324D), c.155A > G (p.D52G), c.1055G > A (p.R352H), c.1064G > A (p.G355E), and c.491 T > C (p.I164T) in GNE. D207V was the most frequent mutation showing an allele frequency of 25%. A total of 21 patients presented classic clinical manifestation, and only 1 patient had signs of proximal muscle weakness. A patient containing p.V603L and p.R160X mutations showed idiopathic thrombocytopenia and distal weakness. There were 4 female patients who experienced rapid deterioration after pregnancy.

Discussion: Our study revealed 7 novel mutations in GNE, where p.D207V was shown as a potential hotspot mutation in Chinese patients. Idiopathic thrombocytopenia should be a concern in GNE myopathy patients. Twenty-seven percent of female patients experienced rapid deterioration during pregnancy or after delivery.
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http://dx.doi.org/10.1007/s10072-022-06023-wDOI Listing
April 2022

Chrysin Ameliorates Influenza Virus Infection in the Upper Airways by Repressing Virus-Induced Cell Cycle Arrest and Mitochondria-Dependent Apoptosis.

Front Immunol 2022 31;13:872958. Epub 2022 Mar 31.

Department of Pharmacy, Department of Immunology, International Cancer Center, Shenzhen University Health Science Center, Shenzhen, China.

Chrysin has been proven to possess antiviral properties, but the precise underlying anti-influenza mechanism and its anti-influenza efficacy are largely unclear. In this study, we investigated the involvement of chrysin in the blockade of cell cycle and apoptosis in distinct cell lines subjected to two H1N1 influenza A virus (IAV) strains, as well as its anti-IAV activity . Here, we found an early unidentified finding that chrysin strongly impeded IAV replication through a mechanism that was autonomous of innate antiviral immune activation and viral protein interaction. Surprisingly, chrysin can suppress IAV-induced cell cycle arrest in the G0/G1 phase by downregulating the expression levels of P53 and P21 while promoting Cyclin D1/CDK4 and Cyclin E1/CDK2 activation. Furthermore, chrysin dramatically inhibited the IAV-triggered mitochondrial apoptotic pathway by altering the balance of Bax/Bcl-xl and reducing caspase-9 and caspase-3 activation. Accumulated reactive oxygen species (ROS) reduction may contribute to the inhibitory role of chrysin in cell cycle arrest and apoptosis following IAV infection. Notably, chrysin preferably inhibited IAV replication in the upper respiratory tract, indicating that it might be a promising drug for restraining the spread of respiratory viruses.
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http://dx.doi.org/10.3389/fimmu.2022.872958DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9009290PMC
April 2022

Norlignans as potent GLP-1 secretagogues from the fruits of Amomum villosum.

Phytochemistry 2022 Jul 11;199:113204. Epub 2022 Apr 11.

State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Yunnan Key Laboratory of Natural Medicinal Chemistry, Kunming, 650201, People's Republic of China.

The dried fruit of Amomum villosum (Amomi Fructus) is an important spices and traditional Chinese medicine. In this study, the EtOH extract of Amomi Fructus was revealed with hypoglycemic effects on db/db mice by increasing plasma insulin levels. After extracted with EtOAc, the EtOAc fraction showed increased activity in stimulating glucagon-like peptide-1 (GLP-1) secretion compared with the EtOH extract. In order to clarify the antidiabetic constituents, four undescribed norlignans, amovillosumins A‒D, were isolated from the EtOAc fraction, and the subsequent chiral resolution yielded three pairs of enantiomers. Their structures were determined by extensive spectroscopic data (1D and 2D NMR, HRESIMS, IR, UV and [α]) and ECD calculations. Amovillosumins A and B significantly stimulated GLP-1 secretion by 375.1% and 222.7% at 25.0 μM, and 166.9% and 62.7% at 12.5 μM, representing a new type of GLP-1 secretagogues.
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http://dx.doi.org/10.1016/j.phytochem.2022.113204DOI Listing
July 2022

Caffeine Citrate Protects Against Sepsis-Associated Encephalopathy and Inhibits the UCP2/NLRP3 Axis in Astrocytes.

J Interferon Cytokine Res 2022 Apr 13. Epub 2022 Apr 13.

Department of Pediatrics, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, P.R. China.

Sepsis-associated encephalopathy (SAE) is a diffuse brain dysfunction without overt central nervous system infection. Caffeine citrate has therapeutic effect on different brain diseases, while its role in SAE remains unclear. The expression levels of interleukin (IL)-18 and IL-1β were upregulated in the cerebrospinal fluid of the subjects. In this study, a rat model of SAE was established by cecal ligation and puncture. Caffeine citrate inhibited SAE-induced neuronal apoptosis and astrocytic activation, decreased reactive oxygen species (ROS) generation, and elevated mitochondrial membrane potential (MMP) level in the cerebral cortex. , primary astrocytes were isolated from rat cerebral cortex and incubated with lipopolysaccharide (LPS) and interferon-γ (IFN-γ). Caffeine citrate reduced ROS and MMP levels and mitochondrial complex enzyme activities in LPS plus IFN-γ-induced astrocytes. Moreover, caffeine citrate inhibited the activation of nucleotide-binding and oligomerization domain (NOD)-like receptor (NLRP3) inflammasome and decreased the production of IL-1β and IL-18 and Notably, caffeine citrate promoted UCP2 expression in astrocytes. The neuroprotective role of UCP2 has been reported in several experimental brain diseases. These results suggest that caffeine citrate inhibits neuronal apoptosis, astrocytic activation, mitochondrial dysfunction in rat cerebral cortex, thereby alleviating SAE. The protection of caffeine citrate against SAE may be achieved by the UCP2-mediated NLRP3 pathway inhibition in astrocytes.
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http://dx.doi.org/10.1089/jir.2021.0241DOI Listing
April 2022

MircroRNA-145 Attenuates Cardiac Fibrosis Via Regulating Mitogen-Activated Protein Kinase Kinase Kinase 3.

Cardiovasc Drugs Ther 2022 Apr 13. Epub 2022 Apr 13.

Pediatric Department, Shanghai General Hospital, No.650 Xinsongjiang Road, Shanghai, 201600, Songjiang District, China.

Purpose: This study aimed to explore the effect of microRNA (miR)-145 on cardiac fibrosis in heart failure mice and its target.

Methods: Experiments were carried out in mice receiving left coronary artery ligation, transverse aortic constriction (TAC), or angiotensin (Ang) II to trigger heart failure, and in cardiac fibroblasts (CFs) with Ang II-induced fibrosis.

Results: The miR-145 levels were decreased in the mice hearts of heart failure induced by myocardial infarction (MI), TAC or Ang II infusion, and in the Ang II-treated CFs. The impaired cardiac function was ameliorated by miR-145 agomiR in MI mice. The increased fibrosis and the levels of collagen I, collagen III, and transforming growth factor-beta (TGF-β) in MI mice were inhibited by miR-145 agomiR or miR-145 transgene (TG). The agomiR of miR-145 also attenuated the increases of collagen I, collagen III, and TGF-β in Ang II-treated CFs. Bioinformatics analysis and luciferase reporter assays indicated that mitogen-activated protein kinase kinase kinase 3 (MAP3K3) was a direct target gene of miR-145. MAP3K3 expression was suppressed by MiR-145 in CFs, while the MAP3K3 over-expression reversed the inhibiting effects of miR-145 agomiR on the Ang II-induced increases of collagen I, collagen III, and TGF-β in CFs.

Conclusion: These results indicated that miR-145 upregulation could improve cardiac dysfunction and cardiac fibrosis by inhibiting MAP3K3 in heart failure. Thus, upregulating miR-145 or blocking MAP3K3 can be used to treat heart failure and cardiac fibrosis.
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http://dx.doi.org/10.1007/s10557-021-07312-wDOI Listing
April 2022

USF1-ATRAP-PBX3 Axis Promote Breast Cancer Glycolysis and Malignant Phenotype by Activating AKT/mTOR Signaling.

Int J Biol Sci 2022 14;18(6):2452-2471. Epub 2022 Mar 14.

Department of Breast Medical Oncology, Harbin Medical University Cancer Hospital, 150 Haping Road, Harbin 150040, China.

Angiotensin II type 1 receptor-associated protein (ATRAP) is widely expressed in different tissues and organs, although its mechanistic role in breast cancer remains unclear. Here, we show that ATRAP is highly expressed in breast cancer tissues. Its aberrant upregulation promotes breast cancer aggressiveness and is positively correlated with poor prognosis. Functional assays revealed that ATRAP participates in promoting cell growth, metastasis, and aerobic glycolysis, while microarray analysis showed that ATRAP can activate the AKT/mTOR signaling pathway in cancer progression. In addition, ATRAP was revealed to direct Ubiquitin-specific protease 14 (USP14)-mediated deubiquitination and stabilization of Pre-B cell leukemia homeobox 3 (PBX3). Importantly, ATRAP is a direct target of Upstream stimulatory factor 1 (USF1), and that ATRAP overexpression reverses the inhibitory effects of USF1 knockdown. Our study demonstrates the broad contribution of the USF1/ATRAP/PBX3 axis to breast cancer progression and provides a strong potential therapeutic target.
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http://dx.doi.org/10.7150/ijbs.69134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8990462PMC
April 2022
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