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Antimicrobial resistance characteristics and phylogenetic relationships of pleuromutilin-resistant Enterococcus isolates from different environmental samples along a laying hen production chain

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Journal of Environmental Sciences 2024年第3期137卷 195-205页

作者： Cong Lin Yuxuan Feng Xianjun Xie Haoyu Zhang Jie Wu Yixiao Zhu Jing Yu Jingyi Feng Wen Su Shanming Lai Anyun Zhang Animal Disease Prevention and Food Safety key laboratory of sichuan province Key Laboratory of Bio-Resource and Eco-Environment of Ministry of EducationCollege of Life SciencesSichuan UniversityChengdu 610065China

Antimicrobial resistance in the laying hen production industry has become a serious public health problem.The antimicrobial resistance and phylogenetic relationships of the common conditional pathogen Enterococcus along the laying hen production chain have not been systematically clarified.105 Enterococcus isolates were obtained from 115 environmental samples (air,dust,feces,fies,sewage,and soil) collected along the laying hen production chain (breeding chicken,chick,young chicken,and commercial laying hen).These Enterococcus isolates exhibited resistance to some clinically relevant antibiotics,such as tetracycline (92.4%),streptomycin (92.4%),and erythromycin (91.4%),and all strains had multidrug resistance phenotypes.Whole genome sequencing characterized 29 acquired antibiotic resistance genes (ARGs) that conferred resistance to 11 classes of antibiotics in 51pleuromutilin-resistant Enterococcus isolates,and lsa(E),which mediates resistance to pleuromutilins,always co-occurred with lnu(B).Alignments with the Mobile Genetic Elements database identified four transposons (Tn554,Tn558,Tn6261,and Tn6674) with several ARGs(erm(A),ant(9)-la,fex(A),and optrA) that mediated resistance to many clinically important antibiotics.Moreover,we identified two new transposons that carried ARGs in the Tn554 family designated as Tn7508 and Tn7492.A complementary approach based on conventional multi-locus sequence typing and whole genome single nucleotide polymorphism analysis showed that phylogenetically related pleuromutilin-resistant Enterococcus isolates were widely distributed in various environments on different production farms.Our results indicate that environmental contamination by antimicrobial-resistant Enterococcus requires greater attention,and they highlight the risk of pleuromutilin-resistant Enterococcus and ARGs disseminating along the laying hen production chain,thereby warranting effective disinfection.

关键词： Antimicrobial resistance Enterococcus Laying hen production chain Pleuromutilin

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The role of vitamin E in polyunsaturated fatty acid synthesis and alleviating endoplasmic reticulum stress in sub-adult grass carp(Ctenopharyngodon idella)

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Animal Nutrition 2024年第1期16卷 275-287页

作者： Ke Yao Lin Feng Wei-Dan Jiang Yang Liu Lu Zhang Hai-Feng Mi Xiao-Qiu Zhou Pei Wu Animal Nutrition Institute Sichuan Agricultural University Fish Nutrition and Safety Production University key laboratory of sichuan province Sichuan Agricultural University key laboratory of Animal Disease-Resistance Nutrition Ministry of Education Ministry of Agriculture and Rural Affairs Key Laboratory of Sichuan Province Tongwei Co. Ltd. Healthy Aquaculture key laboratory of sichuan province

Vitamin E(VE) is an essential lipid-soluble vitamin that improves the fish flesh quality. However, the underlying molecular mechanisms remain unclear. This study aimed to investigate the effects of VE on growth performance and flesh quality in sub-adult grass carp(Ctenopharyngodon idella). A total of 450fish(713.53 ± 1.50 g) were randomly divided into six treatment groups(three replicates per treatment)and fed for nine weeks with different experimental diets(dietary lipid 47.8 g/kg) that contained different levels of VE(5.44, 52.07, 96.85, 141.71, 185.66, and 230.12 mg/kg diet, supplemented as dl-a-tocopherol acetate). Notably, the treatment groups that were fed with dietary VE ranging from 52.07 to230.12 mg/kg diet showed improvement in the percent weight gain, special growth rate, and feed efficiency of grass carp. Moreover, the treatment groups supplemented with dietary VE level of 141.71,185.66, and 230.12 mg/kg diet showed enhancement in crude protein, lipid, and a-tocopherol contents in the muscle, and the dietary levels of VE ranging from 52.07 to 141.71 mg/kg diet improved muscle pH24h and shear force but reduced muscle cooking loss in grass carp. Furthermore, appropriate levels of VE(52.07 to 96.85 mg/kg diet) increased the muscle polyunsaturated fatty acid content in grass carp. Dietary VE also increased the mRNA levels of fatty acid synthesis-related genes, including fas, scd-1, fad,elovl, srebp1, pparγ, and lxra, and up-regulated the expression of SREBP-1 protein. However, dietary VE decreased the expression of fatty acid decomposition-related genes, including hsl, cpt1, acox1, and ppara,and endoplasmic reticulum stress-related genes, including perk, ire1, atf6, eif2a, atf4, xbp1, chop, and grp78, and down-regulated the expression of p-PERK, p-IRE1, ATF6, and GRP78 proteins. In conclusion,dietary VE increased muscle fatty acid synthesis, which may be partly associated with the alleviation of endoplasmic reticulum stress, and ultimately improves fish flesh quality. Moreover, the VE requirements for sub

关键词： Vitamin E Flesh quality Muscle polyunsaturated fatty acid level Endoplasmic reticulum stress Growth performance Grass carp

Synergistic Brønsted Base/Photoredox-Catalyzed Three-Component Coupling with Malonates to Synthesizeδ-Hydroxy Esters andδ-Keto Esters

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Chinese Journal of Chemistry 2024年第9期42卷 957-962页

作者： Ting Li Wei Wang Ming Dong Zhije Zhang Sha Yu Zhengchu Chen Siping Wei Dong Yi Green Pharmaceutical Technology key laboratory of Luzhou City Central Nervous System Drug Key Laboratory of Sichuan ProvinceSchoolof PharmacySouthwestMedicalUniversityLuzhouSichuan 646000China Nuclear Medicine and Molecular Imaging key laboratory of sichuan province LuzhouSichuan 646000China

Multicomponent alkene 1,2-dicarbofunctionalizations(DCFs)have emerged as a powerful strategy to rapidly incorporate both two carbon subunits across one C-C double bond in one step for enhancing molecular complexity and diversity.To the best of our knowledge,there is only one report on photoredox-catalyzed three-component DCFs with malonates through the radical−radical cross-coupling,while photoredox-catalyzed radical-polar crossover(RPC)-type DCFs with malonates were still rare.Herein,we describe a redox-neutral RPC-type 1,2-dialkylation of styrenes with malonates and aldehydes through the synergistic Brønsted base/photoredox catalysis system.This transition-metal-free strategy provides an efficient and clean approach to a broad variety ofδ-hydroxy esters and also features exceptionally mild conditions,wide compatibility of substrate scope and functional groups,and high atomic economy.Moreover,three-component 1,2-alkylacylation from the same starting materials was achieved in one-pot manner through such RPC-type coupling and subsequent two-electron oxidation process,providing a set ofδ-keto esters of interest in pharmaceutical research.

关键词： Alkene difunctionalization Photoredox catalysis Malonates Radical reactions C-C coupling Synthetic methods Aldehydes Alkylation Multicomponentreactions

Activation of autophagy by Citri Reticulatae Semen extract ameliorates amyloid-beta-induced cell death and cognition deficits in Alzheimer’s disease

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Neural Regeneration Research 2024年第11期19卷 2467-2479页

作者： Yong Tang Jing Wei Xiao-Fang Wang Tao Long Xiaohong Xiang Liqun Qu Xingxia Wang Chonglin Yu Xingli Xiao Xueyuan Hu Jing Zeng Qin Xu Anguo Wu Jianming Wu Dalian Qin Xiaogang Zhou Betty Yuen-Kwan Law Dr.Neher’s Biophysics laboratory for Innovative Drug Discovery State Key Laboratory of Quality Research in Chinese MedicineMacao University of Science and TechnologyMacao Special Administrative RegionChina sichuan key Medical laboratory of New Drug Discovery and Druggability Evaluation Luzhou key laboratory of Activity Screening and Druggability Evaluation for Chinese Materia Medica Southwest Medical UniversityLuzhouSichuan ProvinceChina Eye School and key laboratory of sichuan province Ophthalmopathy Prevention&Cure and Visual Function Protection of Chengdu University of TCM ChengduSichuan ProvinceChina School of Basic Medical Sciences Southwest Medical UniversityLuzhouSichuan ProvinceChina Department of Ophthalmology The Affiliated Hospital of Southwest Medical UniversityLuzhouSichuan ProvinceChina Department of Neurology The First People’s Hospital of NeijiangNeijiangSichuan ProvinceChina

Amyloid-beta-induced neuronal cell death contributes to cognitive decline in Alzheimer’s disease.Citri Reticulatae Semen has diverse beneficial effects on neurodegenerative diseases,including Parkinson’s and Huntington’s diseases,however,the effect of Citri Reticulatae Semen on Alzheimer’s disease remains unelucidated.In the current study,the anti-apoptotic and autophagic roles of Citri Reticulatae Semen extract on amyloid-beta-induced apoptosis in PC12 cells were first investigated.Citri Reticulatae Semen extract protected PC12 cells from amyloid-beta-induced apoptosis by attenuating the Bax/Bcl-2 ratio via activation of autophagy.In addition,Citri Reticulatae Semen extract was confirmed to bind amyloid-beta as revealed by biolayer interferometry in vitro,and suppress amyloid-beta-induced pathology such as paralysis,in a transgenic Caenorhabditis elegans in vivo model.Moreover,genetically defective Caenorhabditis elegans further confirmed that the neuroprotective effect of Citri Reticulatae Semen extract was autophagy-dependent.Most importantly,Citri Reticulatae Semen extract was confirmed to improve cognitive impairment,neuronal injury and amyloid-beta burden in 3×Tg Alzheimer’s disease mice.As revealed by both in vitro and in vivo models,these results suggest that Citri Reticulatae Semen extract is a potential natural therapeutic agent for Alzheimer’s disease via its neuroprotective autophagic effects.

关键词： Alzheimer’s disease amyloid-beta apoptosis autophagy Caenorhabditis elegans Citri Reticulatae Semen

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High expression circRALGPS2 in atretic follicle induces chicken granulosa cell apoptosis and autophagy via encoding a new protein

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Journal of Animal Science and Biotechnology 2024年第3期15卷 971-986页

作者： Haorong He Yuanhang Wei Yuqi Chen Xiyu Zhao Xiaoxu Shen Qing Zhu Huadong Yin key laboratory of Livestock and Poultry Multi‑Omics Ministry of Agriculture and Rural AffairsCollege of Animal Science and TechnologySichuan Agricultural UniversityChengduSichuan 611130China Farm Animal Genetic Resources Exploration and Innovation key laboratory of sichuan province Sichuan Agricultural UniversityChengduSichuan 611130China

Background The reproductive performance of chickens mainly depends on the development of follicles.Abnor-mal follicle development can lead to decreased reproductive performance and even ovarian disease among chick-ens.Chicken is the only non-human animal with a high incidence of spontaneous ovarian cancer.In recent years,the involvement of circRNAs in follicle development and atresia regulation has been confirmed.Results In the present study,we used healthy and atretic chicken follicles for circRNA RNC-seq.The results showed differential expression of circRALGPS2.It was then confirmed that circRALGPS2 can translate into a protein,named cir-cRALGPS2-212aa,which has IRES activity.Next,we found that circRALGPS2-212aa promotes apoptosis and autophagy in chicken granulosa cells by forming a complex with PARP1 and HMGB1.Conclusions Our results revealed that circRALGPS2 can regulate chicken granulosa cell apoptosis and autophagy through the circRALGPS2-212aa/PARP1/HMGB1 axis.

关键词： Apoptosis Autophagy Chicken CircRALGPS2 Follicle atresia PARP1 RNC-seq

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All-trans retinoic acid alleviates transmissible gastroenteritis virus-induced intestinal inflammation and barrier dysfunction in weaned piglets

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Journal of Animal Science and Biotechnology 2024年第3期15卷 1131-1144页

作者： Junning Pu Daiwen Chen Gang Tian Jun He Ping Zheng Zhiqing Huang Xiangbing Mao Jie Yu Yuheng Luo Junqiu Luo Hui Yan Aimin Wu Bing Yu Institute of Animal Nutrition Sichuan Agricultural UniversityChengdu 611130SichuanPeople’s Republic of China key laboratory of Animal Disease-Resistance Nutrition Ministry of EducationMinistry of Agriculture and Rural AffairsKey Laboratory of Sichuan Province611130 ChengduSichuanPeople’s Republic of China

Background Transmissible gastroenteritis virus(TGEV)is one of the main pathogens causing severe diarrhea of pig-lets.The pathogenesis of TGEV is closely related to intestinal inflammation.All-trans retinoic acid(ATRA)is the main active metabolite of vitamin A,which has immunomodulatory and anti-inflammatory properties.However,it is unclear whether ATRA can alleviate TGEV-induced intestinal inflammation and barrier dysfunction in piglets.This study aimed to investigate the effects of ATRA on growth performance,diarrhea,intestinal inflammation and intesti-nal barrier integrity of TGEV-challenged piglets.Methods In a 19-d study,32 weaned piglets were randomly divided into 4 treatments:Control group(basal diet),TGEV group(basal diet+TGEV challenge),TGEV+ATRA5 group(basal diet+5 mg/d ATRA+TGEV challenge)and TGEV+ATRA15 group(basal diet+15 mg/d ATRA+TGEV challenge).On d 14,piglets were orally administered TGEV or the sterile medium.Results Feeding piglets with 5 and 15 mg/d ATRA alleviated the growth inhibition and diarrhea induced by TGEV(P<0.05).Feeding piglets with 5 and 15 mg/d ATRA also inhibited the increase of serum diamine oxidase(DAO)activ-ity and the decrease of occludin and claudin-1 protein levels in jejunal mucosa induced by TGEV,and maintained intestinal barrier integrity(P<0.05).Meanwhile,5 mg/d ATRA feeding increased the sucrase activity and the expres-sions of nutrient transporter related genes(GLUT2 and SLC7A1)in jejunal mucosa of TGEV-challenged piglets(P<0.05).Furthermore,5 mg/d ATRA feeding attenuated TGEV-induced intestinal inflammatory response by inhibit-ing the release of interleukin(IL)-1β,IL-8 and tumor necrosis factor-α(TNF-α),and promoting the secretion of IL-10 and secretory immunoglobulin A(sIgA)(P<0.05).Feeding 5 mg/d ATRA also down-regulated the expressions of Toll-like receptors and RIG-I like receptors signaling pathway related genes(TLR3,TLR4,RIG-I,MyD88,TRIF and MAVS)and the phosphorylation level of nuclear factor-κB-p65(NF-κB p65),and up-regulated the inhibitor kappa B alpha(IκBα)p

关键词： All-trans retinoic acid Inflammation Intestinal barrier Piglets Transmissible gastroenteritis virus

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Novel approach of ultrasound-guided lateral recess block for a patient with lateral recess stenosis: A case report

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World Journal of Clinical Cases 2024年第5期12卷 1010-1017页

作者： Jiao Yang Xin-Ling Li Qing-Bing Li Department of Rehabilitation Medicine Center West China HospitalChengdu 610041Sichuan ProvinceChina key laboratory of Rehabilitation Medicine in sichuan province West China HospitalChengdu 610041Sichuan ProvinceChina

BACKGROUND Ultrasound guide technology,which can provide real-time visualization of the needle tip and tissues and avoid many adverse events,is widely used in mini-mally invasive therapy.However,the studies on ultrasound-guided Lateral recess block(LRB)are limited,this is probably because there is no recognized standard method for ultrasound scanning.This study aimed to evaluate the effect of ultrasound-guided LRB in patients with lateral recess stenosis(LRS).CASE SUMMARY A 65-year-old patient complained of low back pain accompanied occasionally by pain and numbness in the left lower limb.Physical examination showed ten-derness on the spinous process and paraspinal muscles from L1 to S1,extensor hallucis longus and tibialis anterior weakness(muscle strength:4-),and a positive straight leg raising test in the left lower limb(60°).Magnetic resonance imaging showed L4–L5 disc degeneration with left LRS and nerve root entrapment.Subsequently,the patient was diagnosed with LRS.This patient was treated with a novel ultrasound-guided LRB approach.The patient’s symptoms significantly improved without any complications at 1 wk postoperatively and at the 3-month follow-up.CONCLUSION This is the first report on the LRS treatment with ultrasound-guided LRB from the contralateral spinous process along the inner side of the articular process by out-plane technique.Further studies are expected to investigate the efficacy and safety of ultrasound-guided LRB for patients with LRS.

关键词： Lateral recess stenosis Ultrasound Lateral recess block Real-time visualization Low back pain Case report

Biomimetic“Gemini nanoimmunoregulators”orchestrated for boosted photoimmunotherapy by spatiotemporally modulating PD-L1 and tumor-associated macrophages

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1345-1361页

作者： Honglin Huang Ningxi Li Xiaodan Wei Qingzhi Li Junhan Guo Geng Yang Hong Yang Lulu Cai Yiyao Liu Chunhui Wu Department of Pharmacy Personalized Drug Therapy Key Laboratory of Sichuan ProvinceSichuan Provincial People’s Hospitaland School of Life Science and TechnologyUniversity of Electronic Science and Technology of ChinaChengdu 610054China TCM Regulating Metabolic Diseases key laboratory of sichuan province Hospital of Chengdu University of Traditional Chinese MedicineChengdu 610072China

A novel strategy of not only stimulating the immune cycle but also modulating the immunosuppressive tumor microenvironment is of vital importance to efficient cancer immunotherapy.Here,a new type of spatiotemporal biomimetic“Gemini nanoimmunoregulators”was engineered to activate robust systemic photoimmunotherapy by integrating the triple-punch of amplified immunogenic cell death(ICD),tumor-associated macrophages(TAMs)phenotype reprogramming and programmed cell death ligand 1(PD-L1)degradation.The“Gemini nanoimmunoregulators”PM@RM-T7 and PR@RM-M2 were constructed by taking the biocompatible mesoporous polydopamine(mPDA)as nanovectors to deliver metformin(Met)and toll-like receptor 7/8 agonist resiquimod(R848)to cancer cells and TAMs by specific biorecognition via wrapping of red blood cell membrane(RM)inlaid with T7or M2 peptides.mPDA/Met@RM-T7(abbreviated as PM@RM-T7)was constructed to elicit an amplified in situ ICD effect through the targeted PTT and effectively stimulated the anticancer immunity.Meanwhile,PD-L1 on the remaining cancer cells was degraded by the burst metformin to prevent immune evasion.Subsequently,mPDA/R848@RM-M2(abbreviated as PR@RM-M2)specifically recognized TAMs and reset the phenotype from M2 to M1 state,thus disrupting the immunosuppressive microenvironment and further boosting the function of cytotoxic T lymphocytes.This pair of sister nanoimmunoregulators cooperatively orchestrated the comprehensive anticancer activity,which remarkably inhibited the growth of primary and distant 4T1 tumors and prevented malignant metastasis.This study highlights the spatiotemporal cooperative modalities using multiple nanomedicines and provides a new paradigm for efficient cancer immunotherapy against metastatic-prone tumors.

关键词： Biomimetic immunoregulator Spatiotemporal delivery Targeted photothermal therapy Amplified immunogenic cell death Immunosuppressive tumor microenvironment PD-L1 degradation TAMs phenotype reversion Metastasis inhibition

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Gossypol acetic acid regulates leukemia stem cells by degrading LRPPRC via inhibiting IL-6/JAK1/STAT3 signaling or resulting mitochondrial dysfunction

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World Journal of Stem Cells 2024年第4期16卷 444-458页

作者： Cheng-Jin Ai Ling-Juan Chen Li-Xuan Guo Ya-Ping Wang Zi-Yi Zhao Department of laboratory Medicine Hospital of Chengdu University of Traditional Chinese MedicineChengdu 641000Sichuan ProvinceChina Department of Ophthalmology Hospital of Chengdu University of Traditional Chinese MedicineChengdu 641000Sichuan ProvinceChina Central laboratory Hospital of Chengdu University of Traditional Chinese MedicineChengdu 641000Sichuan ProvinceChina Traditional Chinese Medicine Regulating Metabolic Diseases key laboratory of sichuan province Chengdu University of Traditional Chinese MedicineChengdu 641000Sichuan ProvinceChina

BACKGROUND Leukemia stem cells(LSCs)are found to be one of the main factors contributing to poor therapeutic effects in acute myeloid leukemia(AML),as they are protected by the bone marrow microenvironment(BMM)against conventional therapies.Gossypol acetic acid(GAA),which is extracted from the seeds of cotton plants,exerts anti-tumor roles in several types of cancer and has been reported to induce apoptosis of LSCs by inhibiting Bcl2.AIM To investigate the exact roles of GAA in regulating LSCs under different microenvironments and the exact mechanism.METHODS In this study,LSCs were magnetically sorted from AML cell lines and the CD34+CD38-population was obtained.The expression of leucine-rich pentatricopeptide repeat-containing protein(LRPPRC)and forkhead box M1(FOXM1)was evaluated in LSCs,and the effects of GAA on malignancies and mitochondrial RESULTS LRPPRC was found to be upregulated,and GAA inhibited cell proliferation by degrading LRPPRC.GAA induced LRPPRC degradation and inhibited the activation of interleukin 6(IL-6)/janus kinase(JAK)1/signal transducer and activator of transcription(STAT)3 signaling,enhancing chemosensitivity in LSCs against conventional chemotherapies,including L-Asparaginase,Dexamethasone,and cytarabine.GAA was also found to downregulate FOXM1 indirectly by regulating LRPPRC.Furthermore,GAA induced reactive oxygen species accumulation,disturbed mitochondrial homeostasis,and caused mitochondrial dysfunction.By inhibiting IL-6/JAK1/STAT3 signaling via degrading LRPPRC,GAA resulted in the elimination of LSCs.Meanwhile,GAA induced oxidative stress and subsequent cell damage by causing mitochondrial damage.CONCLUSION Taken together,the results indicate that GAA might overcome the BMM protective effect and be considered as a novel and effective combination therapy for AML.

关键词： Leukemia stem cells Gossypol acetic acid Reactive oxygen species Mitochondrial dysfunction Interleukin 6/janus kinase 1/signal transducer and activator of transcription 3 signaling