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Melioidosis is an endemic disease in southeast Asia and northern Australia caused by the saprophytic bacteria Burkholderia pseudomallei, with a high mortality rate. The clinical presentation is multifaceted, with symptoms ranging from acute septicemia to multiple chronic abscesses. Here, we report a chronic case of melioidosis in a patient who lived in Malaysia in the 70s and was suspected of contracting tuberculosis. Approximately 40 years later, in 2014, he was diagnosed with pauci-symptomatic melioidosis during a routine examination. Four strains were isolated from a single sample. They showed divergent morphotypes and divergent antibiotic susceptibility, with some strains showing resistance to trimethoprim-sulfamethoxazole and fluoroquinolones. In 2016, clinical samples were still positive for B. pseudomallei, and only one type of strain, showing atypical resistance to meropenem, was isolated. We performed whole genome sequencing and RT-qPCR analysis on the strains isolated during this study to gain further insights into their differences. We thus identified two types of resistance mechanisms in these clinical strains. The first one was an adaptive and transient mechanism that disappeared during the course of laboratory sub-cultures; the second was a mutation in the efflux pump regulator amrR, associated with the overexpression of the related transporter. The development of such mechanisms may have a clinical impact on antibiotic treatment. Indeed, their transient nature could lead to an undiagnosed resistance. Efflux overexpression due to mutation leads to an important multiple resistance, reducing the effectiveness of antibiotics during treatment.

Producing industrially significant compounds with more environmentally friendly represents a challenging task. The large-scale production of an exogenous molecule in a host microfactory can quickly cause toxic effects, forcing the cell to inhibit production to survive. The key point to counter these toxic effects is to promote a gain of tolerance in the host, for instance, by inducing a constant flux of the neo-synthetized compound out of the producing cells. Efflux pumps are membrane proteins that constitute the most powerful mechanism to release molecules out of cells. We propose here a new biological model, Deinococcus geothermalis , organism known for its ability to survive hostile environment; with the aim of coupling the promising industrial potential of this species with that of heterologous efflux pumps to promote engineering tolerance. In this study, clones of D. geothermalis containing various genes encoding chromosomal heterologous efflux pumps were generated. Resistant recombinants were selected using antibiotic susceptibility tests to screen promising candidates. We then developed a method to determine the efflux efficiency of the best candidate, which contains the gene encoding the MdfA of Salmonella enterica serovar Choleraesuis. We observe 1.6 times more compound in the external medium of the hit recombinant than that of the WT at early incubation time. The data presented here will contribute to better understanding of the parameters required for efficient production in D. geothermalis .

Background: Radiation cystitis (RC) results from chronic inflammation, fibrosis, and vascular damage. The urinary symptoms it causes have a serious impact on patients’ quality of life. Despite the improvement in irradiation techniques, the incidence of radiation cystitis remains stable over time, and the therapeutic possibilities remain limited. Mesenchymal stem/stromal cells (MSC) appear to offer2 a promising therapeutic approach by promoting tissue repair through their paracrine action via extracellular vesicles (MSC-EVs) or conditioned medium from human mesenchymal stromal cells (MSC-CM). We assess the therapeutic potential of MSC-EVs or MSC-CM in an in vitro model of RC. Methods:in vitro RC was induced by irradiation of human bladder fibroblasts (HUBF) with the small-animal radiation research platform (SARRP). HUBF were induced towards an RC phenotype after 3 × 3.5 Gy irradiation in the presence of either MSC-EVs or MSC-CM, to assess their effect on fibrosis, angiogenesis, and inflammatory markers. Results: Our data revealed in vitro a higher therapeutic potential of MSC-EVs and MSC-CM in prevention of RC. This was confirmed by down-regulation of α-SMA and CTGF transcription, and the induction of the secretion of anti-fibrotic cytokines, such as IFNγ, IL10 and IL27 and the decrease in the secretion of pro-fibrotic cytokines, IGFBP2, IL1β, IL6, IL18, PDGF, TNFα, and HGF, by irradiated HUBFs, conditioned with MSC-EVs or MSC-CM. The secretome of MSC (MSC-CM) or its subsecretome (MSC-EVs) are proangiogenic, with the ability to induce vessels from HUVEC cells, ensuring the management of bladder vascular lesions induced by irradiation. Conclusion: MSC-EVs and MSC-CM appear to have promising therapeutic potential in the prevention of RC in vitro, by targeting the three main stages of RC: fibrosis, inflammation and vascular damage.

The synthesis of well dispersed cobalt phosphide nanoparticles (NPs) in SBA-15 mesoporous silica by wet impregnation of the molecular cluster [Co 4 (CO) 10 (μ-dppa)] ( 1 ) (dppa = HN(PPh 2 ) 2 ) is described. The thermal activation of the silica impregnated precursor under a H 2 /N 2 (5/95 %) stream at different temperatures to form NPs was studied and it was found that the size of the latter is limited in the 5.5–6.5 nm range by the size of the pores. The obtained materials were characterized by various analytical methods. The porosity and the structure of the mesoporous silica supports were analyzed by N 2 adsorption/desorption and small-angle X-ray diffraction. The nanoparticles were characterized by wide-angle X-ray diffraction, transmission electron microscopy in conventional and scanning modes, electron tomography, energy-dispersive X-ray spectroscopy, and magnetic measurements. Cobalt phosphide NPs of few nanometers were observed in the pores of SBA-15.

In electronic devices based on hybrid materials such as nonvolatile memory elements (NVMEs), it is essential to control precisely the dispersion of metallic nanoparticles (NPs) in an insulating polymer matrix such as polystyrene in order to control the functionality of the device. In this work the incorporation of AuNPs in polystyrene films is controlled by tuning the surface functionalization of the metallic nanoparticles via ligand exchange. Two ligands with different structures were used for functionalization: 1-decanethiol and thiol-terminated polystyrene. This paper presents a versatile method for the modification of gold nanoparticles (AuNPs) with thiol-terminated polystyrene ligands via phase transfer process. An organic colloid of AuNPs ( 5 ± 1 nm diameter) is obtained by the phase transfer process (from water to toluene) that allows exchanging the ligand adsorbed on AuNPs surface (hydrophilic citrate/tannic acid to hydrophobic thiols). The stability, size distribution, and precise location of modified AuNPs in the polymer matrix are obtained from UV-Vis spectroscopy, dynamic light scattering (DLS), and electron tomography. TEM tomographic 3D imaging demonstrates that the modification of AuNPs with thiol-terminated polystyrene results in homogeneous particle distribution in the polystyrene matrix compared to 1-decanethiol modified AuNPs for which a vertical phase separation with a homogeneous layer of AuNPs located at the bottom of the polymer matrix was observed.

Chikungunya virus (CHIKV) is a mosquito-borne pathogen responsible for an acute musculo-skeletal disease in humans. The viral RNA genome replication occurs in membrane spherules named replication organelles (ROs). In this work, we investigate the native structural organization of CHIKV ROs in their cellular context using in situ cryogenic-electron microscopy approaches at late replication stage. We observed previously unreported diameter heterogeneity of ROs at the plasma membrane of infected human cells. CHIKV ROs were only marginally detected in cytopathic vacuoles where they are homogeneous in size, suggesting a finely regulated internalization process. Our data show that ROs maintained at the plasma membrane beyond the first viral cycle are dynamically active both in viral RNA replication, in its export to the cell cytosol, but also in the production of viral proteins. We suggest that late CHIKV ROs have an amplifying role or represent an alternative pathway in the production of infectious viral particles. All these observations bring new insight into the CHIKV life cycle in human cells.Competing Interest StatementThe authors have declared no competing interest.

Worldwide, the leading cause of chronic liver disease is represented by nonalcoholic fatty liver disease (NAFLD) which has now become a global epidemic of the 21st century, affecting 1 in 4 adults, and which appears to be associated with the steadily increasing rates of metabolic syndrome and its components (obesity, type 2 diabetes mellitus (T2DM), and dyslipidemia). NAFLD has been reported to be associated with extrahepatic manifestations such as cardiovascular disease, T2DM, chronic kidney disease, extrahepatic malignancies (e.g., colorectal cancer), endocrine diseases (e.g., hypothyroidism, polycystic ovarian syndrome, psoriasis, and osteoporosis), obstructive sleep apnea, and iron overload. The prevalence of NAFLD is very high, affecting 25–30% of the world population and encloses two steps: (1) nonalcoholic fatty liver (NAFL), which includes steatosis only, and (2) nonalcoholic steatohepatitis (NASH) defined by the presence of steatosis and inflammation with hepatocyte ballooning, with or without fibrosis which can progress to liver fibrosis, hepatocellular carcinoma, and liver transplantation. Current data define a more complex relationship between NAFLD and T2DM than was previously believed, underlining a bidirectional and mutual association between the two entities. This review aims to summarize the current literature regarding the incidence of T2DM among patients with NAFLD and also the prevalence of NAFLD in T2DM patients, highlighting the recent key studies. Clinicians should screen, diagnose, and treat T2DM in patients with NAFLD in order to avoid short- and long-term complications.

Liver cirrhosis is the primary contributor to global mortality associated with chronic liver diseases (CLD). Certain liver infections, including viral hepatitis B (VHB) and C (VHC), alcohol-related liver disease (ALD), and metabolic dysfunction-associated steatotic liver disease (MASLD) are significant contributors to the development of liver cirrhosis. This study aimed to evaluate the prevalence of liver steatosis and fibrosis in individuals with vulnerable conditions. Subjects residing in a rural Romanian county or having lower educational attainment were selected for this study. Following the acquisition of informed consent, a demographic, clinical, and physiological characterization was conducted for each participant. The AUDIT-C questionnaire was obtained from every participant. Transient Elastography (TE) measured liver fibrosis, while blood tests screened for the presence of hepatitis viruses B and C. Among the 571 screened vulnerable subjects, 52.7% were males, and 17.3% were identified as heavy drinkers. Metabolic syndrome was identified in 37.3% of patients and 70% of subjects exhibited a body mass index of ≥ 25 kg/m 2 . Furthermore, 8.5% of participants tested positive for HBs antigen, while 6.1% had HCV antibodies. Additionally, 35.7% of the participants in our study had MASLD, and 7.1% had metabolic dysfunction and alcohol-related liver disease (MetALD) according to the AUDIT-C questionnaire. On TE exams, we found that 9.9% of the participants had advanced fibrosis, 16.1% had cirrhosis, and 24.5% had severe steatosis. Hence, the prevalence of advanced fibrosis and cirrhosis is elevated in asymptomatic healthy individuals from vulnerable conditions in Northeastern Romania, particularly among those with various risk factors. Most of the subjects were identified with MetALD and ALD demonstrating the efficacy of the new nomenclature in identifying the etiology of liver fibrosis.

Nonalcoholic fatty liver disease (NAFLD) has emerged as the most frequent cause of liver disease worldwide, comprising a plethora of conditions, ranging from steatosis to end-stage liver disease. Cardiovascular disease (CVD) has been associated with NAFLD and CVD-related events represent the main cause of death in patients with NAFLD, surpassing liver-related mortality. This association is not surprising as NAFLD has been considered a part of the metabolic syndrome and has been related to numerous CVD risk factors, namely, insulin resistance, abdominal obesity, dyslipidemia, hyperuricemia, chronic kidney disease, and type 2 diabetes. Moreover, both NAFLD and CVD present similar pathophysiological mechanisms, such as increased visceral adiposity, altered lipid metabolism, increased oxidative stress, and systemic inflammation that could explain their association. Whether NAFLD increases the risk for CVD or these diagnostic entities represent distinct manifestations of the metabolic syndrome has not yet been clarified. This review focuses on the relation between NAFLD and the spectrum of CVD, considering the pathophysiological mechanisms, risk factors, current evidence, and future directions.

Acute kidney injury (AKI) is a serious clinical condition that is linked to markedly higher rates of morbidity and mortality in cirrhosis patients. Its diagnosis is challenging due to overlapping clinical and laboratory features among causes such as hepatorenal syndrome (HRS), acute tubular injury (ATI), and prerenal hypovolemia. In order to address the distinct pathophysiology and clinical context of cirrhosis, the definitions and classification of AKI have changed over time, moving from RIFLE and AKIN to KDIGO and ICA-AKI. Because cirrhosis patients have altered muscle mass and fluid retention, traditional markers like serum creatinine (sCr) and urine output have significant limitations. Neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), interleukin-18 (IL-18), and cystatin C (CysC) are some of the new biomarkers that have shown promise in early AKI detection and in differentiating structural from functional kidney injury. NGAL and KIM-1 are sensitive indicators of tubular damage with potential prognostic implications. IL-18 reflects inflammatory injury, and CysC offers a more reliable measure of glomerular filtration. Incorporating these markers may improve early diagnosis, risk stratification, and treatment decisions, representing a key direction for future research in managing AKI in cirrhosis.