Bacterial infection has long been recognized to contribute to struvite urinary stone deposition; however, its contribution to the development of chronic kidney stones has not been extensively ...investigated. In the present study, we hypothesized another possible method of bacteria contributing to the formation of calcium oxalate (CaOx) that accounts for the biggest part of the kidney stone. Bacteria may play important roles by influencing renal Ca
-related ion channel activities, resulting in chronic inflammation of the kidney along with rapid aggregation of stones. We examined the correlation among infection-promoted CaOx kidney stones and alterations in Ca
-related ion channels in an animal model with experimentally induced
and foreign body infection. After the bladder was infected for 7 days, the data demonstrated that stones were presented and induced severe renal tubular breakage as well as altered levels of monocyte chemoattractant protein-1, cyclooxygenase-2, osteopontin, and transient receptor potential vanilloid member 5 expression, reflecting responses of kidney ion channels. Monocyte chemoattractant protein-1, osteopontin, and transient receptor potential vanilloid member 5 expression was significantly downregulated over time, indicating the chronic inflammation phase of the kidney and accelerated aggregation of CaOx crystals, respectively, whereas cyclooxygenase-2 exhibited no differences. These results indicated that bacterial infection is considerably correlated with an alteration in renal Ca
-related ion channels and might support specific and targeted Ca
-related ion channel-based therapeutics for urolithiasis and related inflammatory renal damage.
Display omitted
•A single step solid state crosslinking reaction has been developed to obtain hyaluronic acid hydrogels.•The use of microwave radiation reduces significantly the crosslinking ...time.•The synthesized materials allowed sustained release of a model molecule (methylene blue) for a period of up to 2days.•The material can be used to prepare micro-engineered devices such as microneedles through a micromoulding process.•The resulting hydrogels showed anti-infective and bacteriostatic properties.
Hyaluronic acid (HA) is a natural linear polysaccharide that has been used extensively in the biomedical field as it is a biocompatible, biodegradable, nontoxic and non-immunogenic polymer with high water affinity. Besides, the presence of multiple acid and hydroxyl groups in the HA molecule makes it an ideal candidate for chemical modification. The present paper describes the synthesis and characterization of HA-based hydrogels. For this purpose, aqueous mixtures containing 5% (w/w) of HA and different concentrations of Gantrez S97 (GAN) (1, 3 and 5% w/w) were used to prepare HA-based hydrogels. The mixtures were dried and the hydrogels were obtained after heating the solid material at 80°C for 24h. GAN is the acid form of an methylvinylether and maleic anhydride copolymer and contains multiple acid groups that can form ester bonds when reacting with the multiple hydroxyl groups present in HA chains. The method described here present potential to be applied for the preparation of HA-based biomaterials with a defined form as the crosslinking reaction between HA and the crosslinker takes place in solid phase. Besides, the method can be considered an environmental-friendly process as no organic solvents or potentially toxic substances were used. The esterification reaction was confirmed by infrared spectroscopy and dynamic scanning calorimetry measurements. The loading and release capabilities of the hydrogels were evaluating by using methylene blue (MB) as a model molecule. The hydrogels showed a high affinity for MB showing loadings up to 0.35mg MB per mg of hydrogel. Moreover, the hydrogels were capable of sustaining the MB release over two days. The use of microwave radiation was evaluated to reduce the crosslinking time from 24h to 1h, but this procedure needs to be optimized in future studies. As the crosslinking procedure takes place in solid state, the HA/GAN hydrogels were used to prepare micro-engineered device, microneedle arrays. Finally, the antimicrobial properties of the hydrogels were evaluated. The results showed that the hydrogels presented anti-infective properties.
The increasing adoption of electric vehicles (EVs) presents a promising solution for achieving sustainable transportation and reducing carbon emissions. To keep pace with technological advancements ...in the vehicular industry, this paper proposes the development of a hybrid energy storage system (HESS) and an energy management strategy (EMS) for EVs, implemented using Proteus Spice Ver 8. The HESS consists of a proton exchange membrane fuel cell (PEMFC) as the primary source and a supercapacitor (SC) as the secondary source. The EMS, integrated into an electronic board based on the STM32, utilizes a low-pass filter algorithm to distribute energy between the sources. The accuracy of the proposed PEMFC and SC models is validated by comparing Proteus simulation results with experimental tests conducted on the Bahia didactic bench and Maxwell SC bench, respectively. To optimize energy efficiency, simulations of the HESS system involve adjusting the hybridization rate through changes in the cutoff frequency. The analysis compares the state-of-charge (SOC) of the SC and the voltage efficiency of the fuel cell (FC), across different frequencies to optimize overall system performance. The results highlight that the chosen strategy satisfies the energy demand while preserving the FC’s dynamic performance and optimizing its utilization to the maximum.
Proteus mirabilis is one of the important pathogens of urinary tract and exhibits resistance to multiple drugs. Development of vaccine tends to be the most promising and cost-effective remedy against ...the said pathogen. Herein, we implement a combinatorial approach for screening proteins harboring potential broad-spectrum antigenic epitopes in the proteome of P. mirabilis. The targets are host non-homologous, essential and virulent, and have localization in the extracellular and outer membrane. Immuno-informatics revealed antigenic, surface exposed and broad-spectrum B-cell derived T-cell epitopes for three membrane usher family candidates: AtfC, PMI2533 and PMI1466, which could evoke a substantial immune response. Protein-protein interactions of targeted three proteins have shown their involvement in biologically significant pathways indispensable for the growth and survival of the pathogen. The antigenic epitopes are conserved among all completely annotated strains and docked deeply in the binding cavity of the most prevalent allele-DRB1*0101 in human population. Future work is necessary to characterize the shortlisted proteins and epitopes for immune protection in animal models.
•Vaccine proteins harboring antigenic epitopes against Proteus mirablis are described.•Three novel potential vaccine candidates: AtfC, PMI2533 and PMI1466 are identified.•The proteins and epitopes need to be tested in animal models.
Animal models for host-microbial interactions have proven valuable, yielding physiologically relevant data that may be otherwise difficult to obtain. Unfortunately, such models are lacking or ...nonexistent for many microbes. Here, we introduce organ agar, a straightforward method to enable the screening of large mutant libraries while avoiding physiological bottlenecks. We demonstrate that growth defects on organ agar were translatable to bacterial colonization deficiencies in a murine model. Specifically, we present a urinary tract infection agar model to interrogate an ordered library of
transposon mutants, with accurate prediction of bacterial genes critical for host colonization. Thus, we demonstrate the ability of
organ agar to reproduce
deficiencies. Organ agar was also useful for identifying previously unknown links between biosynthetic genes and swarming motility. This work provides a readily adoptable technique that is economical and uses substantially fewer animals. We anticipate this method will be useful for a wide variety of microorganisms, both pathogenic and commensal, in a diverse range of model host species.
The rapid spread of the
gene is a major public health concern. Here, we describe the multidrug-resistant Proteus mirabilis strain XH1653, which contains a novel SXT/R391 integrative and conjugative ...element (ICE), harboring two tandem copies of
and 21 other resistance genes. XH1653 was resistant to all antibiotics tested, apart from aztreonam. Whole-genome data revealed that two copies of
embedded in the IS
element are located in HS4 of the novel ICE, which we named ICE
ChnXH1653. A circular intermediate of ICE
ChnXH1653 was detected by PCR, and conjugation experiments showed that the ICE can be transferred to the Escherichia coli strain EC600 with frequencies of 1.5 × 10
. In the recipient strain, the ICE exhibited a higher excision frequency and extrachromosomal copy number than the ICE in the donor strain. We also observed that the presence of ICE
ChnXH1653 has a negative impact on bacterial fitness and leads to changes in the transcriptome of the host.
evolution experiments under nonselective conditions showed that the two tandem copies of the IS
element and the IS
element can be lost during repeated laboratory passage. This is the first report of a novel SXT/R391 ICE carrying two tandem copies of
, which also illustrates the role that ICEs may play as platforms for the accumulation and transmission of antibiotic resistance genes.
The occurrence of carbapenemase-producing Proteus mirabilis, especially those strains producing NDM-1 and its variants, is a major public health concern worldwide. The integrative conjugative element (ICE) plays an important role in horizontal acquisition of resistance genes. In this study, we characterized a novel SXT/R391 ICE from a clinical P. mirabilis isolate that we named ICE
ChnXH1653, which contains two tandem copies of the carbapenemase gene
. We performed an integrative approach to gain insights into different aspects of ICE
ChnXH1653 evolution and biology and observed that ICE
ChnXH1653 obtained the carbapenemase gene
by IS
-mediated homologous recombination. Our study reveals that the transmission of
by IS
elements or ICEs may be an important contributor to the carbapenem resistance development across species, which could improve our understanding of horizontal gene transfer in clinical environments.
Proteus species are common opportunistic bacteria and foodborne pathogens. The proper detection of Proteus can effectively reduce the occurrence of food-borne public health events. Proteus mirabilis ...and Proteus vulgaris are the two most important pathogens in the Proteus genus. In this study, a dual TaqMan Real-Time PCR method was established to simultaneously detect and distinguish P. mirabilis and P. vulgaris in samples. The method exhibited good specificity, stability, and sensitivity. Specifically, the minimum detection concentrations of P. mirabilis and P. vulgaris in pure bacterial cultures were 6.08 * 10.sup.2 colony forming units (CFU)/ml and 4.46 * 10.sup.2 CFU/ml, respectively. Additionally, the minimum detectable number of P. mirabilis and P. vulgaris in meat and milk was 10 (3) CFU/g. In addition, the method can be used to distinguish between strains of P. mirabilis and P. vulgaris within two hours. Overall, it is a sensitive, easy-to-use, and practical test for the identification and classification of Proteus in food. Key words: Proteus mirabilis, Proteus vulgaris, TaqMan Real-Time PCR, food-borne pathogens, food poisoning
The emergence and spread of
have greatly weakened the function of tigecycline. Although studies have demonstrated the significance of
as carriers for
, the epidemic mechanism and characteristics of
...in
remain unclear. Herein, we deciphered that the
gene in VRIII of SXT/R391 ICEs was a hotspot for the integration of
-bearing mobile genetic elements by genomic analysis. The mobilization and dissemination of
in
were mediated by highly prevalent ICEs. Furthermore, the co-occurrence of
-bearing ICEs with other chromosomally encoded multidrug resistance gene islands warned that the chromosomes of
are significant reservoirs of ARGs. Overall, our results provide significant insights for the prevention and control of
in
.