Antibiotic resistance in patients with liver cirrhosis:Prevalence and current approach to tackle

Regardless of etiology,complications with bacterial infection in patients with cirrhosis are reported in the range of 25%-46%according to the most recent data.Due to frequent episodes of bacterial infection and repetitive antibiotic treatment,most often with broad-spectrum gram negative coverage,patients with cirrhosis are at increased risk of encountering multidrug resistant bacteria,and this raises concern.In such patients,extended-spectrum beta-lactamase and AmpCproducing Enterobacterales,methicillin-or vancomycin-resistant Staphylococcus aureus,vancomycin-resistant Enterococci,carbapenem-resistant Pseudomonas aeruginosa,and Acinetobacter baumannii,all of which are difficult to treat,are the most common.That is why novel approaches to the prophylaxis and treatment of bacterial infections to avoid antibiotic resistance have recently been developed.At the same time,our knowledge of resistance mechanisms is constantly updated.This review summarizes the current situation regarding the burden of antibiotic resistance,including the prevalence and mechanisms of intrinsic and acquired resistance in bacterial species that most frequently cause complications in patients with liver cirrhosis and recent developments on how to deal with multidrug resistant bacteria.

Field-based evidence for the enrichment of intrinsic antibiotic resistome stimulated by plant-derived fertilizer in agricultural soil

Animal manures have been demonstrated to enhance antibiotic resistance in agricultural soils.However,little is known about the effects of plant-derived fertilizer on soil antibiotic resistome.Herein,metagenomic sequencing was used to investigate the effects of a plantderived fertilizer processed from sugarcane and beet on soil antibiotic resistance genes(ARGs)in a soybean field along crop growth stages.ARG profiles in the soils amended by plant-derived fertilizer were compared with those in the soils amended by chicken manure.The abundance and diversity of total ARGs in the soils amended by plant-derived fertilizer were significantly(P<0.05)elevated at the sprout stage,to a level comparable to that in the manured soils.Whereas,unlike chicken manure mainly introducing manure-borne ARGs to soil,the plant-derived fertilizer was indicated to mainly enrich multidrug resistance genes in soil by nourishing indigenous bacteria.ARGs with abundances in amended soils significantly(P<0.05)higher than in unamended soils at the sprout stage of soybean were considered as enriched ARGs.Decrease in the abundance of the enriched ARGs was observed in both the amended soils from the sprout to the harvest.Network analysis further identified Proteobacteria and Bacteroidetes as the primary bacterial taxa involved in the temporal variation of the enriched ARGs in the soils amended by plant-derived fertilizer,while in manured soils were Firmicutes and Actinobacteria.As revealed by multivariate statistical analyses,variation of the enriched ARGs in the soils amended by plant-derived fertilizer was majorly attributed to the response of co-occurred bacteria to depleting nutrients,which was different from the failed establishment of manure-borne bacteria in the manured soils.Our study provided field-based evidence that plant-derived fertilizer stimulated the intrinsic antibiotic resistome,and proposed attention to the un-perceived risk since some clinically relevant ARGs originate and evolve from natural resistome.

Intrinsic BET inhibitor resistance in SPOP-mutated prostate cancer is mediated by BET protein stabilization and AKT-mTORC1 activation

Subject Code:H16With the support by the National Natural Science Foundation of China,a collaborative study by the research groups led by Prof.Wang Chenji(王陈继)from Fudan University,Prof.Huang Haojie(黄浩杰)from Mayo Clinic and Sun Yinhao(孙颖浩)from the Second Military Medical University have

Correlation between mechano-electronic features and scattering rates using deformation potential theory

This research paper provides valuable insight into the electronic,mechanical and transport properties of the Sr_(2)RuO_(2)F_(2)compound.The study shows that the Sr_(2)RuO_(4)compound exhibits a metallic ground state and that the energy gap widens with oxygen substitution with fluorine.The concept of absolute deformation potential and its correlation with band energies and strains is explained using deformation potential theory.The paper also examines the mechanical features of Sr_(2)RuO_(2)F_(2)using the Voigt-Reuss-Hill approximation method and analyzes its elastic constants,bulk modulus and shear modulus,indicating flexibility and suitability for optoelectronic applications.The role of acoustic phonons in scattering rates and carrier mobility in Sr_(2)RuO_(2)F_(2)and its potential for phonon-mediated superconductivity is investigated.The intrinsic resistivity of electrons and holes under strain and its potential impact on superconductivity and electrical resistivity are also discussed.The insight provided by this study contributes to the current understanding of Sr_(2)RuO_(2)F_(2),and its potential applications.

Approaches to identifying drug resistance mechanisms to clinically relevant treatments in childhood rhabdomyosarcoma

Aim:Despite aggressive multiagent protocols,patients with metastatic rhabdomyosarcoma(RMS)have poor prognosis.In a recent high-risk trial(ARST0431),25% of patients failed within the first year,while on therapy and 80% had tumor progression within 24 months.However,the mechanisms for tumor resistance are essentially unknown.Here we explore the use of preclinical models to develop resistance to complex chemotherapy regimens used in ARST0431.Methods:A Single Mouse Testing(SMT)protocol was used to evaluate the sensitivity of 34 RMS xenograft models to one cycle of vincristine,actinomycin D,cyclophosphamide(VAC)treatment.Tumor response was determined by caliper measurement,and tumor regression and event-free survival(EFS)were used as endpoints for evaluation.Treated tumors at regrowth were transplanted into recipient mice,and the treatment was repeated until tumors progressed during the treatment period(i.e.,became resistant).At transplant,tumor tissue was stored for biochemical and omics analysis.Results:The sensitivity to VAC of 34 RMS models was determined.EFS varied from 3 weeks to>20 weeks.Tumor models were classified as having intrinsic resistance,intermediate sensitivity,or high sensitivity to VAC therapy.Resistance to VAC was developed in multiple models after 2-5 cycles of therapy;however,there were examples where sensitivity remained unchanged after 3 cycles of treatment.Conclusion:The SMT approach allows for in vivo assessment of drug sensitivity and development of drug resistance in a large number of RMS models.As such,it provides a platform for assessing in vivo drug resistance mechanisms at a“population”level,simulating conditions in vivo that lead to clinical resistance.These VAC-resistant models represent“high-risk”tumors that mimic a preclinical phase 2 population and will be valuable for identifying novel agents active against VAC-resistant disease.

Decoding cancer's camouflage: epithelial-mesenchymal plasticity in resistance to immune checkpoint blockade

Epithelial-mesenchymal plasticity(EMP)of cancer cells contributes to cancer cell heterogeneity,and it is well established that EMP is a critical determinant of acquired resistance to cancer treatment modalities including radiation therapy,chemotherapy,and targeted therapies.Here,we aimed to explore how EMP contributes to cancer cell camouflage,allowing an ever-changing population of cancer cells to pass under the radar of our immune system and consequently compromise the effect of immune checkpoint blockade therapies.The ultimate clinical benefit of any combination regimen is evidenced by the sum of the drug-induced alterations observed in the variety of cellular populations composing the tumor immune microenvironment.The finely-tuned molecular crosstalk between cancer and immune cells remains to be fully elucidated,particularly for the spectrum of malignant cells along the epithelial to mesenchymal axis.High-dimensional single cell analyses of specimens collected in ongoing clinical studies is becoming a key contributor to our understanding of these interactions.This review will explore to what extent targeting EMP in combination with immune checkpoint inhibition represents a promising therapeutic avenue within the overarching strategy to reactivate a halting cancer-immunity cycle and establish a robust host immune response against cancer cells.Therapeutic strategies currently in clinical development will be discussed.

Discovery of multi-drug resistant,MCR-1 and ESBL-coproducing ST117 Escherichia coli from diseased chickens in northeast China

An endemic multi-drug resistant ST117 E. coil isolate coproducing MCR-I and 3 ESBL loci was, for the first time, detected from diseased chicken, Liaoning Province, in Northeast China, from 2011 to 2012. Whole- genome sequencing revealed 5 unique plasmids, namely pHXH-1, pHXH-2, pHXH-3, pHXH-4 and pHXH- 5）. Among them, pHXHI and pHXH4 encode ESBL, and pHXH-5 mediates MCR-1 colistin resistance. The results indicate that the potentially-national dissemination of MCR-l-positive pathogens with pan-drug resistance proceeds via food chains.