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1.
Sci Total Environ ; 945: 173803, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-38848923

RESUMO

Vegetation resilience is a key concept for understanding ecosystem responses to disturbances and is essential for maintaining ecosystem sustainability. However, assessing vegetation resilience remains challenging, especially for areas with significant disturbances and ecological restoration, such as surface coal mine ecosystems. Vegetation resilience assessment requires a combination of disturbance magnitude, recovery magnitude, and recovery time. In this study, we propose a vegetation resilience assessment method by integrating disturbance magnitude, recovery magnitude and recovery time. Forty-six surface coal mines in northern China were analysed as the study areas. A geographical detector model was used to explore the influence of climatic factors on vegetation resilience. The results indicated that the vegetation resilience curves included three shapes, inverted U-shaped, S-shaped, and monotonically decreasing, and the different disturbance-recovery relationships of the curves indicated that natural and social factors jointly changed the ecological restoration process. The vegetation resilience of the 46 surface coal mines varies widely, ranging from 0.87 to 7.22, showing a spatial decreasing trend from east to west. The explanatory power of different climatic factors on vegetation resilience by indirectly affecting hydrothermal conditions varies, with the effect of atmospheric pressure being the most significant and the superposition of the two climatic factors enhancing the effect on vegetation resilience. This study enriches the understanding of vegetation resilience assessment and provides important information to guide the differentiation of ecological restoration and resource development of surface coal mines in different regions.

2.
Microbiol Res ; 285: 127769, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38797112

RESUMO

Carbapenem-resistant Klebsiella pneumoniae (CRKP) has emerged as a global threat due to its high mortality in clinical patients. However, the specific mechanisms underlying this increased mortality remain unclear. The objective of this study is to investigate how the development of a resistance phenotype contributes to the significantly higher mortality associated with this pathogen. To achieve this, a collection of isogeneic strains was generated. The clinical carbapenem-susceptible K. pneumoniae (CSKP) strain HKU3 served as the control isolate, while HKU3-KPC was created through conjugation with a blaKPC-2-bearing plasmid and served as clinical CRKP strain. Using a sepsis model, it was demonstrated that both HKU3 and HKU3-KPC exhibited similar levels of virulence. Flow cytometry, RNA-seq, and ELISA analysis were employed to assess immune cell response, M1 macrophage polarization, and cytokine storm induction, revealing that both strains elicited comparable types and levels of these immune responses. Subsequently, meropenem was utilized to treat K. pneumoniae infection, and it was found that meropenem effectively reduced bacterial load, inhibited M1 macrophage polarization, and suppressed serum cytokine production during HKU3 (CSKP) infection. However, these effects were not observed in the case of HKU3-KPC (CRKP) infection. These findings provide evidence that the high mortality associated with CRKP is attributed to its enhanced survival within the host during antibiotic treatment, resulting in a cytokine storm and subsequent host death. The development of an effective therapy for CRKP infections could significantly reduce the mortality caused by this pathogen.


Assuntos
Antibacterianos , Enterobacteriáceas Resistentes a Carbapenêmicos , Carbapenêmicos , Infecções por Klebsiella , Klebsiella pneumoniae , Meropeném , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/patogenicidade , Klebsiella pneumoniae/genética , Infecções por Klebsiella/microbiologia , Infecções por Klebsiella/mortalidade , Infecções por Klebsiella/tratamento farmacológico , Virulência , Antibacterianos/farmacologia , Meropeném/farmacologia , Carbapenêmicos/farmacologia , Animais , Camundongos , Enterobacteriáceas Resistentes a Carbapenêmicos/efeitos dos fármacos , Enterobacteriáceas Resistentes a Carbapenêmicos/genética , Humanos , Macrófagos/microbiologia , Macrófagos/imunologia , beta-Lactamases/genética , beta-Lactamases/metabolismo , Sepse/microbiologia , Sepse/mortalidade , Sepse/tratamento farmacológico , Citocinas/metabolismo , Testes de Sensibilidade Microbiana , Proteínas de Bactérias/genética , Modelos Animais de Doenças , Carga Bacteriana
3.
Microbiol Res ; 285: 127730, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38805981

RESUMO

The tigecycline resistance gene tet(X4) has been widely reported in animals and animal products in some Asian countries including China in recent years but only sporadically detected in human. In this study, we investigated the prevalence and genetic features of tet(X4)-positive clinical E. coli strains. A total of 462 fecal samples were collected from patients in four hospitals located in four provinces in China in 2023. Nine tet(X4)-positive E. coli strains were isolated and subjected to characterization of their genetic and phenotypic features by performing antimicrobial susceptibility test, whole-genome sequencing, bioinformatic and phylogenetic analysis. The majority of the test strains were found to exhibit resistance to multiple antimicrobial agents including tigecycline but remained susceptible to colistin and meropenem. A total of seven different sequence types (STs) and an unknown ST type were identified among the nine tet(X4)-positive strains. Notably, the tet(X4) gene in six out of these nine tet(X4)-positive E. coli strains was located in a IncFIA-HI1A-HI1B hybrid plasmid, which was an tet(X4)-bearing epidemic plasmid responsible for dissemination of the tet(X4) gene in China. Furthermore, the tet(X4) gene in four out of nine tet(X4)-positive E. coli isolates could be successfully transferred to E. coli EC600 through conjugation. In conclusion, this study characterized the epidemic tet(X4)-bearing plasmids and tet(X4)-associated genetic environment in clinical E. coli strains, suggested the importance of continuous surveillance of such tet(X4)-bearing plasmids to control the increasingly widespread dissemination of tigecycline-resistant pathogens in clinical settings in China.


Assuntos
Antibacterianos , Infecções por Escherichia coli , Escherichia coli , Fezes , Testes de Sensibilidade Microbiana , Filogenia , Plasmídeos , Tigeciclina , China/epidemiologia , Escherichia coli/genética , Escherichia coli/efeitos dos fármacos , Escherichia coli/isolamento & purificação , Plasmídeos/genética , Humanos , Infecções por Escherichia coli/microbiologia , Infecções por Escherichia coli/epidemiologia , Antibacterianos/farmacologia , Tigeciclina/farmacologia , Fezes/microbiologia , Prevalência , Sequenciamento Completo do Genoma , Proteínas de Escherichia coli/genética , Genoma Bacteriano , Farmacorresistência Bacteriana Múltipla/genética , Genômica
4.
BMC Genomics ; 25(1): 288, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38500084

RESUMO

BACKGROUND: Larch is an important component of northern forests and a major cultivated tree species in restoration of forest cover using improved seed material. In recent years, the continuous low seed production has severely affected the production of improved variety seedlings and natural regeneration. However, research on the reproductive growth of gymnosperms is extremely scarce. RESULTS: In this study, based on differential transcriptome analysis of two asexual reproductive phases, namely high-yield and low-yield, we further screened 5 ERF family genes that may affect the reproductive development of larch. We analyzed their genetic relationships and predicted their physicochemical properties. The expression patterns of these genes were analyzed in different tissues, developmental stages, hormone treatments, and environmental conditions in hybrid larch. CONCLUSION: The results showed that all 5 genes were induced by low temperature and ABA, and their expression patterns in different tissues suggested a suppressive role in the development of female cones in larch. Among them, LkoERF3-like1 and LkoERF071 may be involved in the flowering age pathway. This study enriches the scarce research on reproductive development in gymnosperms and provides a theoretical basis and research direction for regulating the reproductive development of larch in seed orchards.


Assuntos
Larix , Filogenia , Reprodução/genética , Florestas , Árvores
5.
Adv Sci (Weinh) ; 11(13): e2305277, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38279508

RESUMO

The availability of an ever-expanding portfolio of 2D materials with rich internal degrees of freedom (spin, excitonic, valley, sublattice, and layer pseudospin) together with the unique ability to tailor heterostructures made layer by layer in a precisely chosen stacking sequence and relative crystallographic alignments, offers an unprecedented platform for realizing materials by design. However, the breadth of multi-dimensional parameter space and massive data sets involved is emblematic of complex, resource-intensive experimentation, which not only challenges the current state of the art but also renders exhaustive sampling untenable. To this end, machine learning, a very powerful data-driven approach and subset of artificial intelligence, is a potential game-changer, enabling a cheaper - yet more efficient - alternative to traditional computational strategies. It is also a new paradigm for autonomous experimentation for accelerated discovery and machine-assisted design of functional 2D materials and heterostructures. Here, the study reviews the recent progress and challenges of such endeavors, and highlight various emerging opportunities in this frontier research area.

6.
Sci Total Environ ; 916: 170058, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38218490

RESUMO

The global transmission of carbapenem-resistant Acinetobacter baumannii (CRAB) poses a significant and grave threat to human health. To investigate the potential relationship between hospital sewage and the transmission of CRAB within healthcare facilities, isolates of Acinetobacter spp. obtained from untreated hospital sewage samples were subjected to antimicrobial susceptibility tests, genome sequencing, and bioinformatic and phylogenetic tree analysis, and that data were matched with those of the clinical isolates. Among the 70 Acinetobacter spp. sewage isolates tested, A. baumannii was the most prevalent and detectable in 5 hospitals, followed by A. nosocomialis and A. gerneri. Worryingly, 57.14 % (40/70) of the isolates were MDR, with 25.71 % (18/70) being resistant to carbapenem. When utilizing the Pasteur scheme, ST2 was the predominant type among these CRAB isolates, with Tn2006 (ΔISAba1-blaOXA-23-ATPase-yeeB-yeeA-ΔISAba1) and Tn2009 (ΔISAba1-blaOXA-23-ATPase-hp-parA-yeeC-hp-yeeB-ΔISAba1) being the key mobile genetic elements that encode carbapenem resistance. Seven A. gerneri isolates which harbored Tn2008 (ISAba1-blaOXA-23 -ATPase) and the blaPER-1 gene were also identified. Besides, an A. soil isolate was found to exhibit high-level of meropenem resistance (MIC ≥128 mg/L) and harbor a blaNDM-1 gene located in a core genetic structure of ISAba125-blaNDM-1-ble-trpF-dsbC-cutA. To investigate the genetic relatedness between isolates recovered from hospital sewage and those collected from ICUs, a phylogenetic tree was constructed for 242 clinical isolates and 9 sewage isolates. The results revealed the presence of two evolutionary clades, each containing isolates from both ICU and sewage water, suggesting that CRAB isolates in untreated sewage water were also the transmission clones or closely related evolutionary isolates recoverable in hospital settings. Findings in this work confirm that hospital sewage is a potential reservoir of CRAB.


Assuntos
Infecções por Acinetobacter , Acinetobacter baumannii , Humanos , Acinetobacter baumannii/genética , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , beta-Lactamases/genética , Proteína 1 Semelhante a Receptor de Interleucina-1/genética , Esgotos , Filogenia , Testes de Sensibilidade Microbiana , Infecções por Acinetobacter/tratamento farmacológico , Carbapenêmicos/farmacologia , Hospitais , Adenosina Trifosfatases/genética , Adenosina Trifosfatases/uso terapêutico , Água
7.
Emerg Microbes Infect ; 13(1): 2306957, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38240375

RESUMO

The emergence of carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) poses grave threats to human health. These strains increased dramatically in clinical settings in China in the past few years but not in other parts of the world. Four isogenic K. pneumoniae strains, including classical K. pneumoniae, carbapenem-resistant K. pneumoniae (CRKP), hypervirulent K. pneumoniae (hvKP) and CR-hvKP, were created and subjected to phenotypic characterization, competition assays, mouse sepsis model and rat colonization tests to investigate the mechanisms underlying the widespread nature of CR-hvKP in China. Acquisition of virulence plasmid led to reduced fitness and abolishment of colonization in the gastrointestinal tract, which may explain why hvKP is not clinically prevalent after its emergence for a long time. However, tigecycline treatment facilitated the colonization of hvKP and CR-hvKP and reduced the population of Lactobacillus spp. in animal gut microbiome. Feeding with Lactobacillus spp. could significantly reduce the colonization of hvKP and CR-hvKP in the animal gastrointestinal tract. Our data implied that the clinical use of tigecycline to treat carbapenem-resistant K. pneumoniae infections facilitated the high spread of CR-hvKP in clinical settings in China and demonstrated that Lactobacillus spp. was a potential candidate for anticolonization strategy against CR-hvKP.


Assuntos
Enterobacteriáceas Resistentes a Carbapenêmicos , Infecções por Klebsiella , Camundongos , Humanos , Ratos , Animais , Tigeciclina/farmacologia , Klebsiella pneumoniae/genética , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/epidemiologia , Carbapenêmicos/farmacologia , Virulência , Modelos Animais de Doenças , Antibacterianos/farmacologia
8.
Psychophysiology ; 61(5): e14516, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38214362

RESUMO

Past research showed that emotional contexts can impair recognition memory for the target item. Given that item-context congruity may enhance recognition memory, the present study aims to examine the effect of the congruent emotional encoding contexts on recognition memory. Participants studied congruent word-picture pairs (e.g., the word "cow" - a picture describing a cow) and incongruent word-picture pairs (e.g., the word "cow" - a picture describing a goat) and, subsequently, were asked to report the nature of the picture (emotional or neutral). Behavioral results revealed that emotional contexts impaired source but not item recognition, with congruent word-context mitigating this impairment and enhancing item recognition. Neural results from ERPs and theta oscillations found the recollection process, as shown by the LPC old/new effect and theta oscillations, for both item and source recognition across emotional contexts, irrespective of congruity. Meanwhile, the familiarity process as indexed by the FN400 old/new effect was found only for item recognition in congruent emotional contexts. These findings suggest that the congruent relationship of item-context could mitigate the emotion-induced source memory impairment and enhance item memory, with neural results elucidating the memory processes involved in retrieval of emotional information. Specifically, while emotion-related information generally elicits the recollection-based memory process, only congruent emotional information elicits the familiarity-based process.


Assuntos
Eletroencefalografia , Rememoração Mental , Humanos , Reconhecimento Psicológico , Potenciais Evocados , Emoções
9.
Artigo em Inglês | MEDLINE | ID: mdl-37138476

RESUMO

BACKGROUND: We aimed to evaluate the therapeutic effects of Kechuanning gel plaster on ovalbumin (OVA)-induced rat model of asthma. METHODS: Rats were injected with OVA to induce asthma, and Kechuanning gel plaster was administered after the OVA challenge. The immune cell counts in the bronchial alveolar lavage fluid (BALF) were calculated after Kechuanning gel plaster administration. The levels of immune factors in BALF and serum OVA-specific IgE levels were analyzed. Western blot analysis and immunohistochemistry were carried out to analyze the following proteins: C-FOS, C-JUN, RAS p21 protein activator 1 (RASA1), matrix metalloproteinase 9 (MMP9), RAF1, p-MEK1, tissue inhibitor of metalloproteinase-1 (TIMP1), and p-extracellular signal-regulated kinase 1 (ERK1). RESULTS: Administration of Kechuanning gel plaster led to decreased immune cell counts, inflammatory cytokines (interleukin (IL)-1ß, IL13, and IL17), and OVA-specific IgE expression. Compared to the normal group, the C-FOS, C-JUN, RASA1, MMP9, RAF1, MEK1, TIMP1, and p- ERK1 expressions in the model group were significantly increased, whereas Kechuanning gel plaster administration decreased C-JUN, MMP9, TIMP1, RAF1, MEK1, p-ERK1, C-FOS, and RASA1 protein levels. CONCLUSION: Kechuanning gel plaster exerted its therapeutic effects on OVA-induced asthma model rats through the ERK signaling pathway. Kechuanning gel plaster could be considered as a potential alternative therapeutic agent for the management of asthma.


Assuntos
Asma , Metaloproteinase 9 da Matriz , Ratos , Animais , Camundongos , Ovalbumina/metabolismo , Ovalbumina/farmacologia , Metaloproteinase 9 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/farmacologia , Metaloproteinase 9 da Matriz/uso terapêutico , Sistema de Sinalização das MAP Quinases , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Inibidor Tecidual de Metaloproteinase-1/farmacologia , Inibidor Tecidual de Metaloproteinase-1/uso terapêutico , Asma/induzido quimicamente , Asma/tratamento farmacológico , Citocinas/metabolismo , Imunoglobulina E/metabolismo , Imunoglobulina E/farmacologia , Anti-Inflamatórios/farmacologia , Modelos Animais de Doenças , Camundongos Endogâmicos BALB C , Pulmão/metabolismo
10.
ACS Nano ; 17(22): 22508-22526, 2023 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-37948096

RESUMO

Macrophages are central to the pathogenesis of kidney disease and serve as an effective therapeutic target for kidney injury and fibrosis. Among them, M2-type macrophages have double-edged effects regarding anti-inflammatory effects and tissue repair. Depending on the polarization of the M2 subtypes (M2a or M2c) in the diseased microenvironment, they can either mediate normal tissue repair or drive tissue fibrosis. In renal fibrosis, M2a promotes disease progression through macrophage-to-myofibroblast transition (MMT) cells, while M2c possesses potent anti-inflammatory functions and promotes tissue repair, and is inhibited. The mechanisms underlying this differentiation are complex and are currently not well understood. Therefore, in this study, we first confirmed that M2a-derived MMT cells are responsible for the development of renal fibrosis and demonstrated that the intensity of TGF-ß signaling is a major factor determining the differential polarization of M2a and M2c. Under excessive TGF-ß stimulation, M2a undergoes a process known as MMT cells, whereas moderate TGF-ß stimulation favors the polarization of M2c phenotype macrophages. Based on these findings, we employed targeted nanotechnology to codeliver endoplasmic reticulum stress (ERS) inhibitor (Ceapin 7, Cea or C) and conventional glucocorticoids (Dexamethasone, Dex or D), precisely modulating the ATF6/TGF-ß/Smad3 signaling axis within macrophages. This approach calibrated the level of TGF-ß stimulation on macrophages, promoting their polarization toward the M2c phenotype and suppressing excessive MMT polarization. The study indicates that the combination of ERS inhibitor and a first-line anti-inflammatory drug holds promise as an effective therapeutic approach for renal fibrosis resolution.


Assuntos
Nefropatias , Humanos , Nefropatias/patologia , Macrófagos , Fator de Crescimento Transformador beta/farmacologia , Fibrose , Anti-Inflamatórios/farmacologia
11.
MedComm (2020) ; 4(5): e379, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37789963

RESUMO

To increase the imaging resolution and detection capability, the field strength of static magnetic fields (SMFs) in magnetic resonance imaging (MRI) has significantly increased in the past few decades. However, research on the side effects of high magnetic field is still very inadequate and the effects of SMF above 1 T (Tesla) on B cells have never been reported. Here, we show that 33.0 T ultra-high SMF exposure causes immunosuppression and disrupts B cell differentiation and signaling. 33.0 T SMF treatment resulted in disturbance of B cell peripheral differentiation and antibody secretion and reduced the expression of IgM on B cell membrane, and these might be intensity dependent. In addition, mice exposed to 33.0 T SMF showed inhibition on early activation of B cells, including B cell spreading, B cell receptor clustering and signalosome recruitment, and depression of both positive and negative molecules in the proximal BCR signaling, as well as impaired actin reorganization. Sequencing and gene enrichment analysis showed that SMF stimulation also affects splenic B cells' transcriptome and metabolic pathways. Therefore, in the clinical application of MRI, we should consider the influence of SMF on the immune system and choose the optimal intensity for treatment.

12.
Euro Surveill ; 28(37)2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37707983

RESUMO

BackgroundIn China, the bla NDM gene has been recovered from human bacterial isolates since 2011. After 2014, detections of this gene in animal and food bacterial isolates have increasingly been reported.AimWe aimed to understand how bla NDM-bearing bacteria could spread between humans, animals, and animal-derived food.MethodsA total of 288 non-duplicate Escherichia coli strains, including 130 bla NDM-carrying and 158 bla NDM-negative strains were collected from clinical (humans), food-producing animals (pigs) and food (retail pork) sources between 2015 and 2017. The strains were whole genome sequenced. Core-genome-multilocus-sequence-typing was conducted. To investigate if sequence types (STs) found in human, animal or food samples could have a prior origin in a clinical, animal or food-borne animal reservoir, discriminant analysis of principal components (DAPC) was used. Plasmids bearing bla NDM were characterised.ResultsThe 130 bla NDM-carrying E. coli strains comprised a total of 60 STs, with ST167 (10/51), ST77 (6/33) and ST48 (6/46) being most prevalent in clinical, animal and food sources, respectively. Some ST10 and ST167 strains were respectively found among all three sources sampled, suggesting they might enable transfer of bla NDM between sources. DAPC analysis indicated possible transmissions of ST167 from humans to animals and ST10 from animals to human. In 114 of 130 bla NDM-carrying isolates, bla NDM was located on an IncX3 plasmid.ConclusionThis study in a Chinese context suggests that cross-species transmission of certain STs of E. coli harbouring bla NDM on mobile elements, may facilitate the spread of carbapenem-resistant Enterobacteriaceae. Stringent monitoring of bla NDM-bearing E. coli in ecosystems is important.


Assuntos
Enterobacteriáceas Resistentes a Carbapenêmicos , Ecossistema , Humanos , Animais , Suínos , Escherichia coli/genética , Genômica , China/epidemiologia
14.
Microbiol Spectr ; 11(3): e0426122, 2023 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-37078855

RESUMO

Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is a bacterial pathogen that may cause serious drug-resistant infections that are potentially fatal. To investigate the genetic characteristics of these organisms, we tested 416 P. aeruginosa strains recovered from 12 types of clinical samples collected in 29 different hospital wards in 10 hospitals in Guangdong Province, China, from 2017 to 2020. These strains were found to belong to 149 known sequence types (STs) and 72 novel STs, indicating that transmission of these strains involved multiple routes. A high rate of resistance to imipenem (89.4%) and meropenem (79.4%) and a high prevalence of pathogenic serotypes (76.4%) were observed among these strains. Six STs of global high-risk clones (HiRiCs) and a novel HiRiC strains, ST1971, which exhibited extensive drug resistance, were identified. Importantly, ST1971 HiRiC, which was unique in China, also exhibited high virulence, which alarmed the further surveillance on this highly virulent and highly resistant clone. Inactivation of the oprD gene and overexpression of efflux systems were found to be mainly responsible for carbapenem resistance in these strains; carriage of metallo-ß-lactamase (MBL)-encoding genes was less common. Interestingly, frameshift mutations (49.0%) and introduction of a stop codon (22.4%) into the oprD genes were the major mechanisms of imipenem resistance. On the other hand, expression of the MexAB-OprM efflux pump and MBL-encoding genes were mechanisms of resistance in >70% of meropenem-resistant strains. The findings presented here provide insights into the development of effective strategies for control of worldwide dissemination of CRPA. IMPORTANCE Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is a major concern in clinical settings worldwide, yet few genetic and epidemiological studies on CRPA strains have been performed in China. Here, we sequence and analyze the genomes of 416 P. aeruginosa strains from hospitals in China to elucidate the genetic, phenotypic, and transmission characteristics of CRPA strains and to identify the molecular signatures responsible for the observed increase in the prevalence of CRPA infections in China. These findings may provide new insight into the development of effective strategies for worldwide control of CRPA and minimize the occurrence of untreatable infections in clinical settings.


Assuntos
Antibacterianos , Infecções por Pseudomonas , Humanos , Meropeném/farmacologia , Antibacterianos/farmacologia , Antibacterianos/metabolismo , Carbapenêmicos/farmacologia , Carbapenêmicos/metabolismo , Pseudomonas aeruginosa , Infecções por Pseudomonas/epidemiologia , Infecções por Pseudomonas/microbiologia , Imipenem/farmacologia , Imipenem/metabolismo , beta-Lactamases/genética , beta-Lactamases/metabolismo , Testes de Sensibilidade Microbiana
15.
Comb Chem High Throughput Screen ; 26(4): 778-788, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35611785

RESUMO

BACKGROUND: Asthma is a severe chronic inflammatory airway disease. Kechuanning plaster has excellent efficacy in the treatment of asthma. OBJECTIVE: The aim of this study was to analyze the molecular mechanisms of Kechuanning plaster in the treatment of asthma. METHODS: An asthma model was constructed using Sprague Dawley rats. Differentially expressed genes (DEGs) were screened in three rat groups: the control (normal rats), model (asthma rats), and treatment (asthma rats treated with Kechuanning) groups. After enrichment analysis of the DEGs, the protein-protein interactions (PPIs) of the DEGs were analyzed, and transcription factors and microRNAs (miRNAs) that regulate DEGs were predicted. Finally, western blotting (WB) and immunohistochemical (IHC) analysis was performed to validate protein expression. RESULTS: A total of 745 DEGs were identified and enriched in 93 Gene Ontology terms and 25 Kyoto Encyclopedia of Genes and Genomes pathways. A PPI network, consisting of 224 protein nodes and 368 edges, was constructed. The nuclear factor of activated T cells 2 (NFATc2) was predicted to have binding sites in 61 DEGs. The miRNA-target interaction network included 24 DEGs and 9 miRNAs. WB and IHC analysis demonstrated that the fatty acid-binding protein 5 (FABP5) and the chemokine (C-X-C motif) ligand 3 (CXCL3) had higher expression in the model group and lower expression in the control and treatment groups. CONCLUSION: We concluded that FABP5, CXCL3, suppressor of cytokine signaling 3 (SOCS3), E1A binding protein P300 (EP300), NFATc2, microRNA 495 (miR-495), and miR-30 may play important roles in treating asthma.


Assuntos
Asma , MicroRNAs , Ratos , Animais , Medicina Tradicional Chinesa , Ratos Sprague-Dawley , Perfilação da Expressão Gênica , MicroRNAs/genética , MicroRNAs/metabolismo , Asma/tratamento farmacológico , Asma/genética , Redes Reguladoras de Genes , Transcriptoma , Biologia Computacional
16.
Ann Transl Med ; 10(18): 992, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36267722

RESUMO

Background: Elevated expression of human epididymis protein 4 (HE4) was previously described in connective tissue disease-associated interstitial lung diseases (CTD-ILDs) and cystic fibrosis (CF), but the clinical significance of HE4 has remained unknown in idiopathic pulmonary fibrosis (IPF), which is a progressive fibrosing ILD with a heterogeneous course that is in urgent need of reliable biomarkers in its clinical practice. Methods: A total of 27 IPF patients with acute exacerbation status (AE-IPF), 32 IPF patients with stable status (S-IPF), and 29 sex-age matched healthy controls were retrospectively included. The levels of serum HE4 and Krebs von den Lungen-6 (KL-6) of the 3 cohorts were measured. In addition, the pulmonary expression of HE4 was evaluated in lung transplant specimens of IPF using immunohistochemistry and Western blot, and noncancerous lung tissue resected from early-stage lung cancer patients as controls. The endpoint of follow-up was March 1st, 2022, and the Cox regression model was used to analyze the prognostic value of HE4. Results: The levels of HE4 and KL-6 were obviously elevated in AE-IPF patients compared to S-IPF (296.4 vs. 178.1 pmol/L for HE4, P<0.001; 2,007.0 vs. 990.5 IU/mL for KL-6, P<0.001) or healthy controls (296.4 vs. 51.8 pmol/L for HE4, P<0.001; 2,007.0 vs. 181.0 IU/mL for KL-6, P<0.001). Significant correlations were observed between serum HE4 levels and percent predicted diffusing capacity of the lung for carbon monoxide (DLCO%) (r=-0.526, P<0.001), percent predicted forced vital capacity (FVC%) (r=-0.344, P=0.024), gender-age-physiology (GAP) index (r=0.535, P<0.001), and oxygenation index (r=-0.550, P<0.001) in IPF patients. In histological analysis, overexpression of HE4 in mucosal epithelium of dilated bronchi was observed in IPF patients compared with controls. Multivariate cox regression revealed that serum levels of HE4 [hazard ratio (HR) =1.004, P=0.042] and GAP index (HR =1.374, P=0.010) were associated with worse survival in IPF patients. Conclusions: The expression of serum HE4 was obviously elevated in IPF patients, especially in AE-IPF patients. In addition, serum HE4 could be utilized as a biomarker of disease severity and poor prognosis of IPF patients. These findings warrant further validation in larger, multi-center, and longitudinal cohorts.

17.
iScience ; 25(6): 104428, 2022 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-35663037

RESUMO

We previously reported the recovery of five ST11 carbapenem resistant hypervirulent Klebsiella pneumoniae (CR-HvKP) strains that harbored pLVPK-like virulence plasmids, yet molecular mechanisms underlying acquisition of virulence plasmid by ST11 K. pneumoniae have not been characterized. In this study, we showed that virulence plasmids in these CR-HvKP strains could be transferred to Escherichia coli strain EC600 via conjugation. Transmission of the virulence plasmids was found to involve formation of fusion plasmids with an Incl1 type conjugative plasmid and a small ColRNAI plasmid through homologous recombination and by insertion sequences IS26 and IS903B. The conjugative fusion event would transform different ST types of K. pneumoniae, in particular, the clinically prevalent ST11 or ST258 CRKP into CR-HvKP. Clinical factors that promote or suppress the occurrence of this fusion process should be further investigated to devise new approaches to halt such bacterial evolution trends.

18.
Int J Antimicrob Agents ; 60(2): 106628, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35760224

RESUMO

The continuous emergence of carbapenem-resistant and hypervirulent Klebsiella pneumoniae (CR-hvKP) poses a great challenge to human health owing to the associated extremely high morbidity and mortality. Klebsiella quasipneumoniae is a newly described bacterial species that is often misidentified as K. pneumoniae. Clinical K. quasipneumoniae strains have been reported worldwide, among which multidrug-resistant lineages have become a severe health problem, while less has been understood on this important pathogen. In this study, we characterised three clinical carbapenem-resistant K. quasipneumoniae subsp. similipneumoniae isolates belonging to sequence type 367 (ST367) and capsular type K1 and containing several virulence genes, including salmochelin (iroBCDN), aerobactin (iucABCDiutA) and regulator of mucoid phenotype (rmpA/A2), as well as some resistance genes, including blaKPC-2, blaTEM-1, blaOKP-B-9 and oqxAB. These carbapenem-resistant K. quasipneumoniae subsp. similipneumoniae strains containing virulence genes exhibited a higher level of virulence and serum resistance than a classical K. pneumoniae strain, while their virulence levels were slightly lower compared with typical ST11 CR-hvKP and ST23 K1 hvKP strains. This study reports for the first time the genetic and virulence characterisation of clinical K. quasipneumoniae subsp. similipneumoniae strains that simultaneously contained blaKPC-2 and virulence genes, contributing to a better understanding of their resistance and pathogenicity as well as for epidemic surveillance worldwide.


Assuntos
Enterobacteriáceas Resistentes a Carbapenêmicos , Infecções por Klebsiella , Antibacterianos/farmacologia , Enterobacteriáceas Resistentes a Carbapenêmicos/genética , Carbapenêmicos/farmacologia , Humanos , Klebsiella , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae , Plasmídeos/genética , Virulência/genética
19.
Emerg Microbes Infect ; 11(1): 1730-1741, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35730377

RESUMO

Acinetobacter baumannii is one of the key Gram-negative pathogens that can cause serious nosocomial infections. In China, a large proportion of clinical A. baumannii strains are multidrug resistant, among which strains resistant to carbapenems are particularly worrisome, as infections caused by such strains may limit the choice of existing antibiotics. We conducted a nationwide and genome-based surveillance on the prevalence and antibiotic susceptibility profile of carbapenem-resistant A. baumannii (CRAB) strains collected from intensive care units (ICUs) in hospitals in different provinces and investigated the routes of transmission and mechanism of resistance by whole-genome sequencing and phylogenetic analysis. We found that CRAB strains were prevalent in 71.4% (55/77) of the ICUs surveyed. Clonal spread of CRAB was found in 37.6% (29/77) of ICUs and a total of 22 different clones were identified. Most clones were transmissible within one ICU, but up to six clones could be detected in at least three hospitals. In addition, carbapenem-hydrolysing class D ß-lactamases (CHDL) were found to be mainly responsible for carbapenem-resistance in A. baumannii and the ST2 global-clone is the predominant type of CRAB in China. Importantly, we found that CRAB isolates currently exhibited an extremely low rate of resistance to colistin (0.4%) and tigecycline (2.5%), but a high rate of resistance to ceftazidime-avibactam (70.2%). Findings in this work shall facilitate development of appropriate antimicrobial regimens for treatment of CRAB infections. Further surveillance and research on the evolutionary and epidemiological features of clinical CRAB strains are necessary.


Assuntos
Infecções por Acinetobacter , Acinetobacter baumannii , Infecções por Acinetobacter/tratamento farmacológico , Infecções por Acinetobacter/epidemiologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Proteínas de Bactérias/genética , Carbapenêmicos/farmacologia , Carbapenêmicos/uso terapêutico , Hospitais , Humanos , Unidades de Terapia Intensiva , Testes de Sensibilidade Microbiana , Filogenia , beta-Lactamases/genética
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