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Alzheimer's disease (AD) is characterised by progressive neurodegeneration with the formation of amyloid beta (Aβ) plaques and neurofibrillary tau tangles in the brain parenchyma. The causes of AD have been attributed to a combination of age-related changes within the brain as well as genetic, environmental and lifestyle factors. However, a recent study by Banerjee et al. highlights the possibility that AD may be a transmissible disease and that iatrogenic AD could be environmentally acquired, similar to iatrogenic Creutzfeldt-Jakob disease (iCJD). The study reports that contaminated Aβ in cadaver-derived pituitary growth hormone (c-hGH) therapy, which patients received during childhood inoculation, may accidentally transmit into their brains, triggering neurodegeneration and AD onset in older age. Furthermore, corroborating evidence from various animal model studies and human case reports suggests that AD can be potentially transmissible.

Parkinson's disease (PD) is the second most common neurodegenerative disease in the world. Currently, PD is incurable, and the diagnosis of PD mainly relies on clinical manifestations. The central pathological event in PD is the abnormal aggregation and deposition of misfolded α-synuclein (α-Syn) protein aggregates in the Lewy body (LB) in affected brain areas. Behaving as a prion-like seeding, the misfolded α-syn protein can induce and facilitate the aggregation of native unfolded α-Syn protein to aggravate α-Syn protein aggregation, leading to PD progression. Recently, in a blood-based α-Syn seeding amplification assay (SAA), Kluge et al. identified pathological α-Syn seeding activity in PD patients with Parkin (PRKN) gene variants. Additionally, pathological α-syn seeding activity was also identified in sporadic PD and PD patients with Leucine-rich repeat kinase 2 (LRRK2) or glucocerebrosidase (GBA) gene variants. Principally, the α-Syn SAA can be used to detect pathological α-Syn seeding activity, which will significantly enhance PD diagnosis, progression monitoring, prognosis prediction, and anti-PD therapy. The significance and future strategies of α-Syn SAA protocol are highlighted and proposed, whereas challenges and limitations of the assay are discussed.

Background: Coffee and tea consumption account for most caffeine intake and 2-3 billion cups are taken daily around the world. Caffeine dependence is a widespread but under recognized problem., Objectives: To conduct a systematic review on the genetic susceptibility factors affecting caffeine metabolism and caffeine reward and their association with caffeine intake., Methodology: We conducted PubMed and Embase searches using the terms "caffeine", "reward", "gene", "polymorphism", "addiction", "dependence" and "habit" from inception till 2024. The demographics, genetic and clinical data from included studies were extracted and analyzed. Only case-control studies on habitual caffeine drinkers with at least 100 in each arm were included., Results: A total of 2552 studies were screened and 26 studies involving 1,851,428 individuals were included. Several genes that were involved with caffeine metabolism such as CYP1A2, ADORA2A, AHR, POR, ABCG2, CYP2A6, PDSS2 and HECTD4 rs2074356 (A allele specific to East Asians and monomorphic in Europeans, Africans and Americans) were associated with habitual caffeine consumption with effect size difference of 3% to 32% in number of cups of caffeinated drink per day per effect allele. In addition, ALDH2 was linked to the Japanese population. Genes associated with caffeine reward included BDNF, SLC6A4, GCKR, MLXIPL and dopaminergic genes such as DRD2 and DAT1 which had around 2-5% effect size difference in number of cups of caffeinated drink for each allele per day., Conclusion: Several genes that were involved in caffeine metabolism and reward were associated with up to 30% effect size difference in number of cups of caffeinated drink per day, and some associations were specific to certain ethnicities. Identification of at-risk caffeine dependence individuals can lead to early diagnosis and stratification of at-risk vulnerable individuals such as pregnant women and children, and can potentially lead to development of drug targets for dependence to caffeine., (© 2024. The Author(s).)

Gilliam Autism Rating Scale-Third Edition (GARS-3) serves as an effective screening tool for autism spectrum disorder (ASD) that is based on the latest and authoritative diagnostic criteria, however, there is a deficiency in adaptive research in China. We aimed to revise the Chinese version of GARS-3 (CV-GARS-3) and evaluate its psychometric characteristics, providing a theoretical basis for the improvement of ASD screening tools in China. This study developed CV-GARS-3 through translation and cultural adaptation of GARS-3. 362 ASD individuals, 126 typical development individuals, and 103 individuals with other disorders were recruited to analyze the psychometric characteristics of CV-GARS-3. The results showed that exploratory structural equation model demonstrated satisfactory goodness-of-fit. Within the non-verbal ASD samples, all items loaded on anticipated factors. Regarding verbal ASD samples, 3 items exhibited considerable cross-loadings and were categorized under unexpected factors. Meanwhile, acceptable criterion validity was reflected in the four subscales (r = 0.71) and the six subscales (r = 0.74). Satisfactory reliability was observed in the four subscales (Cronbach's α = 0.96, inter-rater consistency = 0.86, test-retest consistency = 0.87) and the six subscales (Cronbach's α = 0.94, inter-rater consistency = 0.81, test-retest consistency = 0.81). In addition, receiver operating characteristic analysis demonstrated that both the four subscales (sensitivity = 89%, specificity = 85%, accuracy = 88%) and the six subscales (sensitivity = 86%, specificity = 88%, accuracy = 86%) had outstanding screening effects. Therefore, the results suggested that the CV-GARS-3 is considered as a useful tool for the screening and auxiliary diagnosis of ASD. Notably, the expression of scale should be further improved to adapt the context of Chinese culture and achieve more precise diagnostic results., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Alzheimer's disease (AD) is the most common neurodegenerative disorder that affects the cerebral cortex and hippocampus, and is characterised by progressive cognitive decline and memory loss. A recent report of a patient carrying a novel gain-of-function variant of RELN (H3447R, termed RELN-COLBOS) who developed resilience against presenilin-linked autosomal-dominant AD (ADAD) has generated enormous interest. The RELN-COLBOS variant enhances interactions with the apolipoprotein E receptor 2 (ApoER2) and very-low-density lipoprotein receptor (VLDLR), which are associated with delayed AD onset and progression. These findings were validated in a transgenic mouse model. Reelin is involved in neurodevelopment, neurogenesis, and neuronal plasticity. The evidence accumulated thus far has demonstrated that the Reelin pathway links apolipoprotein E4 (ApoE4), amyloid-β (Aβ), and tubulin-associated unit (Tau), which are key proteins that have been implicated in AD pathogenesis. Reelin and key components of the Reelin pathway have been highlighted as potential therapeutic targets and biomarkers for AD., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

There are currently no disease-modifying therapies for Parkinson's disease (PD), a progressive neurodegenerative disorder associated with dopaminergic neuronal loss. There is increasing evidence that endogenous dopamine (DA) can be a pathological factor in neurodegeneration in PD. Tyrosine hydroxylase (TH) is the key rate-limiting enzyme for DA generation. Drugs that inhibit TH, such as alpha-methyltyrosine (α-MT), have recently been shown to protect against neurodegeneration in various PD models. DA receptor agonists can activate post-synaptic DA receptors to alleviate DA-deficiency-induced PD symptoms. However, DA receptor agonists have no therapeutic effects against neurodegeneration. Thus, a combination therapy with DA receptor agonists plus TH inhibitors may be an attractive therapeutic approach. TH inhibitors can protect and promote the survival of remaining dopaminergic neurons in PD patients' brains, whereas DA receptor agonists activate post-synaptic DA receptors to alleviate PD symptoms. Additionally, other PD drugs, such as N-acetylcysteine (NAC) and anticholinergic drugs, may be used as adjunctive medications to improve therapeutic effects. This multi-drug cocktail may represent a novel strategy to protect against progressive dopaminergic neurodegeneration and alleviate PD disease progression., Competing Interests: The authors declare no conflicts of interest.

Long non-coding RNAs (lncRNAs) have attracted significant scientific attention due to their central role in regulating gene expression and their profound impact on the intricate mechanisms of ovarian function. These versatile molecules exert their influence through various mechanisms, including the coordination of transcription processes, modulation of post-transcriptional events, and the shaping of epigenetic landscapes. Furthermore, lncRNAs function as competitive endogenous RNAs (ceRNAs), engaging in intricate interactions with microRNAs (miRNAs) to finely adjust the expression of target genes. The intricate lncRNA-miRNA-mRNA network serves as a crucial determinant in governing the multifaceted physiological functions of the ovaries. It holds substantial potential in unraveling the causes and progression of reproductive disorders and, importantly, in identifying new therapeutic targets and diagnostic markers for these conditions. A comprehensive comprehension of lncRNAs and their ceRNA activities within the domain of ovarian biology could potentially lead to groundbreaking advancements in clinical interventions and management strategies. This exploration of lncRNAs and their intricate involvement in the regulatory framework provides an extensive platform for deciphering the complex nature of ovarian physiology and pathology. The ongoing progress in this field, which encompasses in-depth investigations into the functional roles of specific lncRNAs, the elucidation of their complex interactions with miRNAs, and the comprehensive profiling of their expression patterns, holds the promise of making significant contributions to our understanding of ovarian biology and reproductive disorders. Ultimately, these breakthroughs will have wide-ranging translational implications, paving the way for the development of precision therapies and personalized medicine strategies to address the myriad challenges in the realm of reproductive health., Competing Interests: All authors declare that there are no competing interests., (© 2023 The Authors.)

A pathological feature of Parkinson's disease (PD) is the progressive loss of dopaminergic neurons and decreased dopamine (DA) content in the substantia nigra pars compacta in PD brains. DA is the neurotransmitter of dopaminergic neurons. Accumulating evidence suggests that DA interacts with environmental and genetic factors to contribute to PD pathophysiology. Disturbances of DA synthesis, storage, transportation and metabolism have been shown to promote neurodegeneration of dopaminergic neurons in various PD models. DA is unstable and can undergo oxidation and metabolism to produce multiple reactive and toxic by-products, including reactive oxygen species, DA quinones, and 3,4-dihydroxyphenylacetaldehyde. Here we summarize and highlight recent discoveries on DA-linked pathophysiologic pathways, and discuss the potential protective and therapeutic strategies to mitigate the complications associated with DA., (© 2023. Ruijin Hospital, Shanghai Jiao Tong University.)

To understand the heavy metal pollution status of Dongjiang Lake, the contents and species of heavy metals in the surface sediments were investigated during September 2021, and the heavy metal pollution level and potential ecological risk were evaluated. The results showed that Cd, Pb, As, Cu, Zn, Ni, and Cr contents were in the range of 0.40-34.1, 14.8-1688, 6.99-1155, 6.89-280, 26.2-1739, 6.29-55.4, and 23.3-44.8 mg·kg -1 , respectively, with extremely uneven spatial distributions. The highest contents of Cd, Pb, As, Zn, Cu, and Ni were found in the site adjacent to Yaogangxian tungsten ore. The proportion of metal species with bioavailability was high, in which Cd in acid-soluble species was 46.7%-71.5% and Pb in reducible species was 46.8%-67.0%. The bioavailable species of Cu, Zn, Ni, and Cr were 35%-68%, 42%-72%, 26%-51%, and 6%-30%, respectively, although they primarily existed in residual species. According to the geo-accumulation index ( I geo ), there was a moderate or extreme pollution status of Cd in all sites, moderate or extreme pollution status of Pb in 90% of sites, and moderate pollution status of As, Cu, and Zn in 30% of sites. The ecological risk factor ( E r i ) of Cd showed high potential ecological risk in all sites with significantly high potential ecological risk in 80% of sites. Moreover, As and Pb had significantly high potential ecological risk, and Cu had moderate potential ecological risk in S7, which was adjacent to Yaogangxian tungsten ore. There was a high total potential ecological risk in all sites and significantly high potential ecological risk in 50% of sites. Therefore, the surface sediments of Dongjiang Lake were under the combined pollution of Cd, Pb, As, Zn, and Cu with high bioavailability and high total potential ecological risk.

Conjugative plasmids play a vital role in bacterial evolution and promote the spread of antibiotic resistance. They usually cause fitness costs that diminish the growth rates of the host bacteria. Compensatory mutations are known as an effective evolutionary solution to reduce the fitness cost and improve plasmid persistence. However, whether the plasmid transmission by conjugation is sufficient to improve plasmid persistence is debated since it is an inherently costly process. Here, we experimentally evolved an unstable and costly mcr-1 plasmid pHNSHP24 under laboratory conditions and assessed the effects of plasmid cost and transmission on the plasmid maintenance by the plasmid population dynamics model and a plasmid invasion experiment designed to measure the plasmid's ability to invade a plasmid-free bacterial population. The persistence of pHNSHP24 improved after 36 days evolution due to the plasmid-borne mutation A51G in the 5'UTR of gene traJ . This mutation largely increased the infectious transmission of the evolved plasmid, presumably by impairing the inhibitory effect of FinP on the expression of traJ . We showed that increased conjugation rate of the evolved plasmid could compensate for the plasmid loss. Furthermore, we determined that the evolved high transmissibility had little effect on the mcr-1 -deficient ancestral plasmid, implying that high conjugation transfer is vital for maintaining the mcr-1 -bearing plasmid. Altogether, our findings emphasized that, besides compensatory evolution that reduces fitness costs, the evolution of infectious transmission can improve the persistence of antibiotic-resistant plasmids, indicating that inhibition of the conjugation process could be useful to combat the spread of antibiotic-resistant plasmids. IMPORTANCE Conjugative plasmids play a key role in the spread of antibiotic resistance, and they are well-adapted to the host bacteria. However, the evolutionary adaptation of plasmid-bacteria associations is not well understood. In this study, we experimentally evolved an unstable colistin resistance ( mcr-1 ) plasmid under laboratory conditions and found that increased conjugation rate was crucial for the persistence of this plasmid. Interestingly, the evolved conjugation was caused by a single-base mutation, which could rescue the unstable plasmid from extinction in bacterial populations. Our findings imply that inhibition of the conjugation process could be necessary for combating the persistence of antibiotic-resistance plasmids., Competing Interests: The authors declare no conflict of interest.

Neel et al. identified pathophysiologic clues linking gasdermin-E (GSDME) with frontotemporal dementia and amyotrophic lateral sclerosis. 1 Therapeutic studies targeting GSDME may provide a viable approach for neurodegenerative diseases., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Meltblown nonwoven materials have gained attention due to their excellent filtration performance. The research on the performance of the intercalation meltblown preparation process is complex and a current research focus in the field of chemical production. Based on data related to intercalated and unintercalated meltblown materials under given process conditions, a product performance prediction model of intercalated meltblown materials was established under different process parameters (receiving distance, hot air velocity). The structural variables (thickness, porosity, and compressive resilience), the change in product performance, and the relationship between structural variables and product performance (filtration resistance, efficiency, air permeability) after intercalation were studied. Multiple regression analysis was used to analyze the structural variables, and evaluation of the regression results were made using R2, MSE, SSR, and SST. A BP neural network prediction model for product performance was established. The BP neural network model was used to find the maximum filtration efficiency. The study provides theoretical support for regulating product performance by solving the maximum filtration efficiency using BP neural network model., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Xu, Xu, Yi, Yuan and Cai.)

This study investigated the influence of carrier oils on the in vitro and in vivo bioavailability of PTE encapsulated in scallop gonad protein isolates (SGPIs)-epigallocatechin gallate (EGCG) conjugate stabilized emulsions. The SGPIs-EGCG stabilized emulsions were subjected to an in vitro simulated digestion, and the resulting corn oil and MCT micelles were used to evaluate the PTE transportation using the Caco-2 cell model. Both emulsions remarkably improved the bioaccessibility of PTE in the micelle phase. Nevertheless, corn oil emulsions increased trans-enterocyte transportation of PTE more efficiently than MCT emulsions. Furthermore, the maximum plasma concentrations of PTE and its metabolites in mice fed with PTE emulsions were prominently higher than those in mice fed with PTE solution, while the in vivo metabolic patterns of PTE in different oil-stabilized emulsions were different. Therefore, SGPIs-EGCG stabilized emulsions could enhance the bioavailability of PTE through controlled release, in which corn oil is more suitable than MCT.

Doxorubicin is an anthracycline widely used for the treatment of various cancers; however, the drug has a common deleterious side effect, namely a dose-dependent cardiotoxicity. Doxorubicin treatment increases the generation of reactive oxygen species, which leads to oxidative stress in the cardiac cells and ultimately DNA damage and cell death. The most common DNA lesion produced by oxidative stress is 7,8-dihydro-8-oxoguanine (8-oxoguanine), and the enzyme responsible for its repair is the 8-oxoguanine DNA glycosylase (OGG1), a base excision repair enzyme. Here, we show that the OGG1 deficiency has no major effect on cardiac function at baseline or with pressure overload; however, we found an exacerbation of cardiac dysfunction as well as a higher mortality in Ogg1 knockout mice treated with doxorubicin. Our transcriptomic analysis also showed a more extensive dysregulation of genes in the hearts of Ogg1 knockout mice with an enrichment of genes involved in inflammation. These results demonstrate that OGG1 attenuates doxorubicin-induced cardiotoxicity and thus plays a role in modulating drug-induced cardiomyopathy., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Chukwuemeka George Anene-Nzelu et al.)

The plasmid-encoded colistin resistance gene mcr-1 challenges the use of polymyxins and poses a threat to public health. Although IncI2-type plasmids are the most common vector for spreading the mcr-1 gene, the mechanisms by which these plasmids adapt to host bacteria and maintain resistance genes remain unclear. Herein, we investigated the regulatory mechanism for controlling the fitness cost of an IncI2 plasmid carrying mcr-1. A putative ProQ/FinO family protein encoded by the IncI2 plasmid, designated as PcnR (plasmid copy number repressor), balances the mcr-1 expression and bacteria fitness by repressing the plasmid copy number. It binds to the first stem-loop structure of the repR mRNA to repress RepA expression, which differs from any other previously reported plasmid replication control mechanism. Plasmid invasion experiments revealed that pcnR is essential for the persistence of the mcr-1-bearing IncI2 plasmid in the bacterial populations. Additionally, single-copy mcr-1 gene still exerted a fitness cost to host bacteria, and negatively affected the persistence of the IncI2 plasmid in competitive co-cultures. These findings demonstrate that maintaining mcr-1 plasmid at a single copy is essential for its persistence, and explain the significantly reduced prevalence of mcr-1 following the ban of colistin as a growth promoter in China., (© The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Although the respiratory and immune systems are the major targets of Coronavirus Disease 2019 (COVID-19), acute kidney injury and proteinuria have also been observed. Currently, detailed pathologic examination of kidney damage in critically ill patients with COVID-19 has been lacking. To help define this we analyzed kidney abnormalities in 26 autopsies of patients with COVID-19 by light microscopy, ultrastructural observation and immunostaining. Patients were on average 69 years (19 male and 7 female) with respiratory failure associated with multiple organ dysfunction syndrome as the cause of death. Nine of the 26 showed clinical signs of kidney injury that included increased serum creatinine and/or new-onset proteinuria. By light microscopy, diffuse proximal tubule injury with the loss of brush border, non-isometric vacuolar degeneration, and even frank necrosis was observed. Occasional hemosiderin granules and pigmented casts were identified. There were prominent erythrocyte aggregates obstructing the lumen of capillaries without platelet or fibrinoid material. Evidence of vasculitis, interstitial inflammation or hemorrhage was absent. Electron microscopic examination showed clusters of coronavirus-like particles with distinctive spikes in the tubular epithelium and podocytes. Furthermore, the receptor of SARS-CoV-2, ACE2 was found to be upregulated in patients with COVID-19, and immunostaining with SARS-CoV nucleoprotein antibody was positive in tubules. In addition to the direct virulence of SARS-CoV-2, factors contributing to acute kidney injury included systemic hypoxia, abnormal coagulation, and possible drug or hyperventilation-relevant rhabdomyolysis. Thus, our studies provide direct evidence of the invasion of SARSCoV-2 into kidney tissue. These findings will greatly add to the current understanding of SARS-CoV-2 infection., (Copyright © 2020 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Background: The population of end-stage renal failure (ESRF) receiving dialysis treatment is increasing worldwide. For most patients with ESRF, dialysis can extend their life. However, treatment can be demanding and time-consuming. Despite dialysis treatment, many patients continue to experience various sufferings., Methods: A qualitative study was conducted with semi-structured interviews to explore the experiences of suffering of ESRF patients on maintenance dialysis in Malaysia. The results were thematically analyzed., Results: Nineteen ESRF patients were interviewed. The themes and subthemes were: (I) physical suffering-physical symptoms and functional limitations, (II) psychological suffering-the emotions and thoughts of suffering, (III) social suffering-healthcare-related suffering and burdening of others and (IV) spiritual suffering-the queries of suffering., Conclusions: These findings may help healthcare professionals to fill in the gaps in the delivery of best renal palliative care.

Background: It is well-recognized that injection of iodinated radiographic contrast media (CM) sometimes causes acute renal injury via multiple mechanisms, such as vasoconstriction, toxicity on glomerular endothelium and tubular epithelium and so forth., Case Presentation: A 51-year-old man developed acute renal injury with proteinuria after CM administration. To our surprise, in his renal biopsy sample the myelin figure like structure was observed in glomerular endothelium and mesangial cells by transmission electron microscopy. However the patient didn't has any clinic clues of Fabry disease and other lysosomal storage disorders. Moreover in vitro cultured glomerular endothelial and mesangial cells we found CM triggers lipid aggregation along with the increased CD36 and decreased ABCA1 abundance. Thus this patient was administrated statin to correct the aberrant lipid trafficking, 2 months later at his next visit we found his renal function partially recovered with reduced proteinuria., Conclusions: Besides the well-known underlying mechanisms, CM may cause renal impairment by triggering the dysregulated transportation of lipid. Furthermore statin is suggested to be a very promising medicine to decrease side effects of CM.

The objective of this study was to assess the impact of diverse plasmids bearing colistin resistance gene mcr-1 on host fitness. Forty-seven commensal E. coli isolates recovered from the pig farm where mcr-1 was first identified were screened for mcr-1. mcr-1 -bearing plasmids were characterized by sequencing. The fitness impact of mcr-1 -bearing plasmids was evaluated by in vitro competition assays. Twenty-seven (57.5%) E. coli isolates were positive for mcr-1 . The mcr-1 genes were mainly located on plasmids belonging to IncI2 ( n = 5), IncX4 ( n = 11), IncHI2/ST3 ( n = 8), IncFII ( n = 2), and IncY ( n = 2). InHI2 plasmids also carried other resistance genes ( floR, bla CTX-M , and fosA3 ) and were only detected in isolates from nursery pigs. Sequences of the representative mcr-1 -bearing plasmids were almost identical to those of the corresponding plasmid types reported previously. An increase in the fitness of IncI2- and IncX4-carrying strains was observed, while the presence of IncHI2, IncFII and IncY plasmids showed a fitness cost although an insignificant fitness increase was initially observed in IncFII or IncY plasmids-containing strains. Acquisition of IncI2-type plasmid was more beneficial for host E. coli DH5α than either IncHI2 or IncX4 plasmid, while transformants with IncHI2-type plasmid presented a competitive disadvantage against IncI2 or IncX4 plasmid containing strains. In conclusion, IncI2, IncX4, and IncHI2 were the major plasmid types driving the dissemination of mcr-1 in this farm. Increased fitness or co-selection by other antimicrobials might contribute to the further dissemination of the three epidemic mcr-1 -positive plasmids (IncI2, IncX4, and IncHI2) in this farm and worldwide.

mcr-1, the first plasmid-mediated colistin-resistance gene, can mediate polymyxin resistance and be transferred horizontally via plasmids. Many studies have confirmed its distribution via epidemic plasmids (IncI2, IncX4, IncHI2, etc.), as well as mobile genetic elements, among Enterobacteriaceae isolated from animals, humans, and the environment in 35 countries. These studies provide the basis of understanding the complicated mechanism of colistin resistance mediated by MCR-1 and its global dissemination and epidemic properties, and also enrich antimicrobial resistance mechanisms. Here, we review the latest advances in the prevalence, resistance mechanism, transfer mechanism, and genetic environments of mcr-1 in isolates recovered from various samples worldwide. Finally, we discuss the clinical risk and the corresponding solutions, aiming to provide a basis for researchers and clinical scientists to face the serious challenge of antimicrobial resistance together.

As a kind of Phthalate esters ( PEs ), Di-n-butyl phthalate ( DBP ) is widely employed as plasticizers in the production of polymeric materials. The concentration variation of DBP/n-hexane solution was studied by monitoring the chroma evolution of infrared absorption spectra in conjunction with spectral analysis by using two-dimensional-correlation spectroscopy. Absorption peaks at 742，1 078，1 123，1 281，1 467，1 728，2 873，2 933，2 961 cm(-1) was gained with Fourier transform infrared spectra. The IR spectra was divided into three bands: 400～1 200, 1 200～1 900 and 2 900～4 000 cm(-1), correlation between the absorption peaks and the sequential order of the changes in spectral intensity extracted from synchronous and asynchronous plots indicated that some bong vibrations in 1 123 cm(-1) (Benzene ring surface vibration and OCO bending vibration ), 1 728 cm(-1) (CO bending vibration), 2 873, 2 961 cm(-1) (CH3 concertina movement ) and 3 436 cm(-1) (C—H bending vibration in plane of Benzene) is sensitive to the concentration of DBP. This result showed that the chroma evolution of infrared absorption spectra in conjunction with spectral analysis using two-dimensional-correlation spectroscopy can accurately analyze the concentration of DBP in n-hexane. This research provides a theoretical basis to the detection and analysis of DBP.

Di-n-butyl phthalate (DBP) is one kind of Phthalate esters (PEs) widely employed as plasticizers in the production of polymeric materials. PEs are dialkyl and alkyl aryl esters of 1,2-Benzenedi-carboxylic acid, which comprise a wide group of compounds. Since these compounds are not linked to the polymeric matrix, they can migrate from their original containers to the surrounding environment, resulting in ubiquitous environmental pollutants. The infrared vibration spectra of isolated DBP was assigned according to DFT calculations by Gaussesview 5.0 software with First Principles. The method of B3LYP of the density functional theory (DFT) at 6-31G* level has been used to calculate its geometrical parameters and convergence criteria. Compared with the Fourier transform infrared spectrum of DBP in 400~4 000 cm-1 band, the characteristic absorption peaks of the simulation spectrum were broadly in agreement, and the position of the peaks were almost corresponding to each other. Considering the influence of the experimental conditions and temperature, theoretical calculations were in good agreement with experimental data. According to the linear fitting of the peak position of the experimental spectra with respect to the theoretical spectra, the correlation degree is more than 99%. This research provides a theoretical basis to the detection and analysis of DBP.

A new micellar electrokinetic chromatography method with large-volume sample stacking and polarity switching was developed to analyze amoxicllin, cephalexin, oxacillin, penicillin G, cefazolin, and cefoperazone in milk and egg. The important parameters influencing separation and enrichment factors were optimized. The optimized running buffer consisted of 10 mM phosphate and 22 mM SDS at pH 6.7. The sample size was 1.47 kPa × 690 s, the reverse voltage was 20 kV, and the electric current recovery was 95%. Under these optimum conditions, the enrichment factors of six β-lactams were 193-601. Their LODs were <0.26 ng/g, and LOQs were all 2 ng/g, which was only 1/50-1/2 of the maximum residual limits demanded by U.S. and Japanese regulations. The intraday and interday RSDs of method were lower than 3.70 and 3.91%, respectively. The method can be applied to determine these six antibiotic residues in egg and milk.

Background: Until now, polymyxin resistance has involved chromosomal mutations but has never been reported via horizontal gene transfer. During a routine surveillance project on antimicrobial resistance in commensal Escherichia coli from food animals in China, a major increase of colistin resistance was observed. When an E coli strain, SHP45, possessing colistin resistance that could be transferred to another strain, was isolated from a pig, we conducted further analysis of possible plasmid-mediated polymyxin resistance. Herein, we report the emergence of the first plasmid-mediated polymyxin resistance mechanism, MCR-1, in Enterobacteriaceae., Methods: The mcr-1 gene in E coli strain SHP45 was identified by whole plasmid sequencing and subcloning. MCR-1 mechanistic studies were done with sequence comparisons, homology modelling, and electrospray ionisation mass spectrometry. The prevalence of mcr-1 was investigated in E coli and Klebsiella pneumoniae strains collected from five provinces between April, 2011, and November, 2014. The ability of MCR-1 to confer polymyxin resistance in vivo was examined in a murine thigh model., Findings: Polymyxin resistance was shown to be singularly due to the plasmid-mediated mcr-1 gene. The plasmid carrying mcr-1 was mobilised to an E coli recipient at a frequency of 10(-1) to 10(-3) cells per recipient cell by conjugation, and maintained in K pneumoniae and Pseudomonas aeruginosa. In an in-vivo model, production of MCR-1 negated the efficacy of colistin. MCR-1 is a member of the phosphoethanolamine transferase enzyme family, with expression in E coli resulting in the addition of phosphoethanolamine to lipid A. We observed mcr-1 carriage in E coli isolates collected from 78 (15%) of 523 samples of raw meat and 166 (21%) of 804 animals during 2011-14, and 16 (1%) of 1322 samples from inpatients with infection., Interpretation: The emergence of MCR-1 heralds the breach of the last group of antibiotics, polymyxins, by plasmid-mediated resistance. Although currently confined to China, MCR-1 is likely to emulate other global resistance mechanisms such as NDM-1. Our findings emphasise the urgent need for coordinated global action in the fight against pan-drug-resistant Gram-negative bacteria., Funding: Ministry of Science and Technology of China, National Natural Science Foundation of China., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Nematophagous fungi are considered to have the best potential as biological agents for the control of gastrointestinal nematodes in domestic animals. However, relatively few studies have been conducted with the genus Monacrosporium, especially with strains native to China. In the present study, we isolated and identified nematophagous fungi from fresh sheep feces. A pure fungal strain was molecularly characterized, and its nematophagous activity was evaluated. The morphological plasticity of the isolated strain, as well as its interaction with the nematode targets, was observed by scanning electron microscopy of the infected Trichostrongylus colubriformis L3 and the free-living nematode Caenorhabditis elegans. Three isolated fungal strains from the 30 fresh fecal samples of sheep from Inner Mongolia, China exhibited predatory activity; however, only a single strain was successfully purified (SF 0459). The SF 0459 strain was characterized by morphological analysis of its conidia and sequencing of its ITS1-5.8S rDNA-ITS2 region. This strain was identified to be Monacrosporium salinum (GenBank ID: KP036623). Nematophagous fungus helper bacteria were found at the interaction points between fungi and nematodes. The percentage of live T. colubriformis L3 was reduced by 83.79-88.69% based on the in vitro assay., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The nematophagous fungus Duddingtonia flagrans has been investigated as a biological agent for the control of gastrointestinal nematodes infecting domestic animals in other countries. However, D. flagrans has not been detected in China. In this study 1,135 samples were examined from 2012 to 2014; 4 D. flagrans isolates (SDH 035, SDH 091, SFH 089, SFG 170) were obtained from the feces of domestic animals and dung compost. The 4 isolates were then characterized morphologically. The SDH 035 strain was characterized by sequencing the ITS1-5.8S rDNA-ITS2 region. A BLAST search showed that the SDH 035 strain (GenBank KP257593) was 100% identical to Arthrobotrys flagrans (AF106520) and was identified as D. flagrans. The morphological plasticity of the isolated strain and the interaction of this strain with the nematode targets were observed by subjecting the infected trichostrongylide L3 to scanning electron microscopy. At 6 and 8 hr after trichostrongylide L(3) was added, hyphal ramifications were observed and L(3) were captured, respectively. Scanning electron micrographs were obtained at 0, 6, 12, 18, 24, 30, 36, 42, and 48 hr, where 0 is the time when trichostrongylide L(3) were first captured by the fungus. The details of the capture process by the fungus are also described. Chlamydospores were observed in the body of L(3) in the late stage of digestion. A sticky substance and bacteria could be observed in contact areas between predation structures and nematode cuticle.