Today, Klebsiella pneumoniae strains are sophisticatedly associated with the transmission of KPC, and ST11 clones carrying KPC-2 are an important target for anti-infective clinical therapy, posing a ...very high threat to patients. To present the detailed genetic features of two KPC-2 core structures of F94_plasmid pA, the whole genome of K. pneumoniae strain F94 was sequenced by nanopore and illumina platform, and mobile genetic elements associated with antibiotic-resistance genes were analyzed with a series of bioinformatics methods. K. pneumoniae strain F94, identified as a class A carbapenemase-resistant Enterobacteriaceae, was resistant to most tested antibiotics, especially to low-levels of ceftazidime/avibactam (avibactam ≤ 4 mg/L), owing to overexpression of the two KPC-2 in F94_plasmid pA. However, strain F94 was sensitive to high-levels of ceftazidime/avibactam (avibactam ≥ 8 mg/L), which correlated with further inhibition of ceftazidime hydrolysis by the KPC-2 enzyme due to the multiplication of avibactam. Collinearity analysis indicated that multi-drug resistance (MDR) regions of plasmids with the tandam repeats of two or more KPC-2 core structures share highly similar structures. This study characterized the MDR region of the F94_ plasmid pA as homologous to plasmids pKPC2_090050, pKPC2_090374, plasmid unnamed 2, pC2414-2-KPC, pKPC2-020037, pBS1014-KPC2, pKPC-J5501, and pKPC2-020002, which contained the tandem repeats of one, two, or more KPC-2 core structures, providing insight into the evolution of multidrug resistance in K. pneumoniae. An alternative theoretical basis for exploring the tandem repeats of two or more KPC-2 core structures was developed by analyzing and constructing the homologous sequence of F94_ plasmid pA.
Osteoarthritis (OA) is a common orthopedic disorder, and its incidence has been increasing among young adults in recent years. The purpose of this study is to investigate the global, regional, and ...national trends in OA burden and variation among individuals aged 30 to 44 from 1990 to 2019.
Data on the incidence, prevalence, and years lived with disability (YLDs) related to OA were sourced from the Global Burden of Disease Study 2019 among individuals aged 30 to 44. These measures were stratified by gender, region, country, and socio-demographic index (SDI). Additionally, we analyzed YLDs attributable to risk factors.
In 2019, there were a total of 32,971,701 cases of OA among individuals aged 30 to 44 years worldwide, with an additional 7,794,008 new incident cases reported. OA of the knee was the primary contributor to both incidence and prevalence rates over the past three decades. From 1990 to 2019, both males and females in countries with high SDI and high-middle SDI showed upward trends in age-standardized incidence, prevalence, and YLDs rates. In 2019, the United States of America had the highest age-standardized incidence, prevalence, and YLDs rates. Elevated body-mass index (BMI) was found to be the most prevalent risk factor for osteoarthritis-related YLDs. Age-standardized YLDs rates were positively associated with SDI.
OA remains a significant disease burden on individuals aged 30 to 44, with modifiable risk factors such as unhealthy lifestyle and obesity representing key targets for future interventions aimed at reducing the impact of this condition on younger generations.
The objective was to investigate the effect of nonprotein nitrogen source, dietary protein supply, and genetic yield index on methane emission, N metabolism, and ruminal fermentation in dairy cows. ...Forty-eight Danish Holstein dairy cows (24 primiparous cows and 24 multiparous cows) were used in a 6 × 4 incomplete Latin square design with 4 periods of 21-d duration. Cows were fed ad libitum with the following 6 experimental diets: diets with low, medium, or high rumen degradable protein (RDP):rumen undegradable protein (RUP) ratio (manipulated by changing the proportion of corn meal, corn gluten meal, and corn gluten feed) combined with either urea or nitrate (10 g NO3−/kg of dry matter) as nonprotein nitrogen source. Samples of ruminal fluid and feces were collected from multiparous cows, and total-tract nutrient digestibility was estimated using TiO2 as flow marker. Milk samples were collected from all 48 cows. Gas emission (CH4, CO2, and H2) was measured by 4 GreenFeed units. We observed no significant interaction between dietary RDP:RUP ratio and nitrate supplementation, and between nitrate supplementation and genetic yield index on CH4 emission (production, yield, intensity). As dietary RDP:RUP ratio increased, intake of crude protein, RDP, and neutral detergent fiber and total-tract digestibility of crude protein linearly increased, and RUP intake linearly decreased. Yield of milk, energy-corrected milk, and milk protein and lactose linearly decreased, whereas milk fat and milk urea nitrogen concentrations linearly increased as dietary RDP:RUP ratio increased. The increase in dietary RDP:RUP ratio resulted in a linear increase in the excretion of total purine derivatives and N in urine, but a linear decrease in N efficiency (milk N in % of N intake). Nitrate supplementation reduced dry matter intake (DMI) and increased total-tract organic matter digestibility compared with urea supplementation. Nitrate supplementation resulted in a greater reduction in DMI and daily CH4 production and a greater increase in daily H2 production in multiparous cows compared with primiparous cows. Nitrate supplementation also showed a greater reduction in milk protein and lactose yield in multiparous cows than in primiparous cows. Milk protein and lactose concentrations were lower for cows receiving nitrate diets compared with cows receiving urea diets. Nitrate supplementation reduced urinary purine derivatives excretion from the rumen, whereas N efficiency tended to increase. Nitrate supplementation reduced proportion of acetate and propionate in ruminal volatile fatty acids. In conclusion, no interaction was observed between dietary RDP:RUP ratio and nitrate supplementation, and no interaction between nitrate supplementation and genetic yield index on CH4 emission (production, yield, intensity) was noted. Nitrate supplementation resulted in a greater reduction in DMI and CH4 production, and a greater increase in H2 production in multiparous cows than in primiparous cows. As the dietary RDP:RUP ratio increased, CH4 emission was unaffected and RDP intake increased, but RUP intake and milk yield decreased. Genetic yield index did not affect CH4 production, yield, or intensity.
Direct asymmetric reductive amination is one of the most efficient methods for the construction of chiral amines, in which the scope of the applicable amine coupling partners remains a significant ...challenge. In this study we describe primary alkyl amines effectively serve as the N-sources in direct asymmetric reductive amination catalyzed by the iridium precursor and sterically tunable chiral phosphoramidite ligands. The density functional theory studies of the reaction mechanism imply the alkyl amine substrates serve as a ligand of iridium strengthened by a (N)H-O(P) hydrogen-bonding attraction, and the hydride addition occurs via an outer-sphere transition state, in which the Cl-H H-bonding plays an important role. Through this concise procedure, cinacalcet, tecalcet, fendiline and many other related chiral amines have been synthesized in one single step with high yields and excellent enantioselectivity.
Nano-hydroxyapatite and its composites(nHA) have been widely used as grafts in inter-vertebral fusion. However, the safety and efficacy of the graft in inter-vertebral fusion is controversial. This ...meta-analysis aimed at evaluating the safety and efficacy of nHA and non-hydroxyapatite grafts (noHA) (autologous bone, etc.) in inter-body fusion.
A comprehensive search was performed in electronic database as follows: PubMed, EMBASE, the Cochrane Library, Web of Science, and China National Knowledge Internet (CNKI) from inception until October 2022. Clinical studies on the effect of nHA and noHA in spinal fusion were collected. Analysis of outcome indicators using RevMan 5.4 statistical software.
The meta-analysis showed that the operation time of patients who underwent inter-body fusion with nHA grafts was less than that of patients who underwent noHA (p < 0.05). Compared with the noHA group, the nHA group can achieve similar clinical effects in the fusion rate(OR = 1.29,95%CI: 0.88 to 1.88,p = 0.19),Subsidence rate(OR = 1.2,95%CI:0.44 to 3.28,p = 0.72), inter-vertebral space height(SMD = 0.04,95%CI:-0.08 to 0.15,p = 0.54),Cobb angle(SMD = 0.21,95%CI: 0.18 to 0.6,p = 0.21),Blood loss(SMD = -36.58,95%CI: -81.45 to 8.29,p = 0.11),operative time in 12 months(SMD = -5.82,95%CI: -9.98 to -1.67,p = 0.006) and in the final follow-up(SMD = -0.38,95%CI: -0.51 to -0.26,p < 0.00001),ODI(SMD = 0.68,95%CI: -0.84 to 2.19,p = 0.38), VAS(SMD = 0.17,95%CI: -0.13 to 0.48,p = 0.27) and adverse events(OR = 0.98,95%CI: 0.66 to 1.45,p = 0.92), and the differences are not statistically significant.
This meta-analysis suggests that nHA matrix grafts are similar to noHA grafts in the safety and efficacy of spinal reconstruction, and are an ideal material for inter-vertebral bone grafting.
Bone marrow mesenchymal stem cells (BMSCs) exhibit the capacity to self-renew and differentiate into multi-lineage cell types, including osteoblasts, which are crucial regulators of fracture healing. ...Thus, this study aims to investigate the effect of microRNA (miR)-22-3p from BMSC-derived EVs on osteogenic differentiation and its underlying mechanism.
Extracellular vesicles (EVs) were isolated from BMSCs and taken up with BMSCs. Dual-luciferase reporter gene assay was used to verify the binding relationship between miR-22-3p and FTO. Loss- and gain-of-function experiments were performed to determine the roles of EV-delivered miR-22-3p and FTO in osteogenic differentiation as well as their regulatory role in the MYC/PI3K/AKT axis. To determine the osteogenic differentiation, ALP and ARS stainings were conducted, and the levels of RUNX2, OCN, and OPN level were determined. In vivo experiment was conducted to determine the function of EV-delivered miR-22-3p and FTO in osteogenic differentiation, followed by ALP and ARS staining.
miR-22-3p expression was repressed, while FTO expression was elevated in the ovariectomized mouse model. Overexpression of miR-22-3p, EV-delivered miR-22-3p, increased ALP activity and matrix mineralization of BMSCs and promoted RUNX2, OCN, and OPN expressions in BMSCs. miR-22-3p negatively targeted FTO expression. FTO silencing rescued the suppressed osteogenic differentiation by EV-delivered miR-22-3p inhibitor. FTO repression inactivated the MYC/PI3K/AKT pathway, thereby enhancing osteogenic differentiation both in vivo and in vitro.
In summary, miR-22-3p delivered by BMSC-derived EVs could result in the inhibition of the MYC/PI3K/AKT pathway, thereby promoting osteogenic differentiation via FTO repression.
Background
Today, the
bla
NDM
gene is widely distributed on several plasmids from a variety of Gram-negative bacteria, primarily in transposons and gene cassettes within their multidrug-resistant ...(MDR) regions. This has led to the global dissemination of the
bla
NDM
gene.
Methods
The determination of class A beta-lactamase, class B and D carbapenemases was performed according to the recommendations of the Clinical and Laboratory Standards Institute (CLSI). Antimicrobial susceptibility testing was performed using both the BioMerieux VITEK2 system and antibiotic paper diffusion methods. Plasmid transfer was then evaluated by conjugation experiments and plasmid electroporation assays. To comprehensively analyze the complete genome of
K. pneumoniae
strain F11 and to investigate the presence of mobile genetic elements associated with antibiotic resistance and virulence genes, Nanopore and Illumina sequencing platforms were used, and bioinformatics methods were applied to analyze the obtained data.
Results
Our findings revealed that
K. pneumoniae
strain F11 carried class A beta-lactamase and classes B+D carbapenemases, and exhibited resistance to commonly used antibiotics, particularly tigecycline and ceftazidime/avibactam, due to the presence of relevant resistance genes. Plasmid transfer assays demonstrated successful recovery of plasmids pA_F11 and pB_F11, with average conjugation frequencies of 2.91×10
-4
and 1.56×10
-4
, respectively. However, plasmids pC_F11 and pD_F11 failed in both conjugation and electroporation experiments. The MDR region of plasmid pA_F11 contained rare In1765, Tn
As2
, and Tn
As3
elements. The MDR2 region of plasmid pB_F11 functioned as a mobile genetic “island” and lacked the
bla
NDM-1
gene, serving as a “bridge” connecting the early composite structure of
ble
MBL
and
bla
NDM-1
to the recent composite structure. Additionally, the MDR1 region of plasmid pB_F11 comprised In27, Tn
As1
, Tn
As3
, and Tn
2
; and plasmid pC_F11 harbored the recent composite structure of
ble
MBL
and
bla
NDM-1
within Tn
3000
which partially contained partial Tn
125
.
Conclusion
This study demonstrated that complex combinations of transposons and integron overlaps, along with the synergistic effects of different drug resistance and virulence genes, led to a lack of effective therapeutic agents for strain F11, therefore its dissemination and prevalence should be strictly controlled.
Maternal obesity affects the risk of cardiovascular disease and inflammatory response in offspring. However, the impact of maternal obesity on offspring with Kawasaki disease (KD), the leading cause ...of childhood acquired heart disease, is still an understudied area. This study aimed to elucidate the impact of maternal obesity on offspring in KD-like vasculitis and the underlying mechanisms. Offspring of obese female mice and normal diet dams were randomly divided into two subgroups. The pups were injected intraperitoneally with either Candida albicans water-soluble fraction (CAWS) or phosphate buffered saline (PBS) to establish the obesity (OB)-CAWS group, OB group, wild type (WT)-CAWS group, and WT group. Their weight was monitored during the study. After four weeks, echocardiography was applied to obtain the alternation of cardiac structures. Mouse cytokine panel, Hematoxylin-Eosin (HE) staining, western blot, and real-time qPCR were used to study the pathological changes and protein and RNA expression alternations. Based on the study of pathology, serology and molecular biology, maternal obesity lead to more severe vasculitis and induced altered cardiac structure in the offspring mice and promoted the expression of pro-inflammatory cytokines through activating the NF-κB signaling pathway. Maternal obesity aggravated the inflammatory response of offspring mice in KD-like vasculitis.
Quantifying full left ventricular (LV) metrics including cavity area, myocardium area, cavity dimensions and wall thicknesses from cardiac magnetic resonance (MR) images, and then assessing regional ...and global cardiac function plays a crucial role in clinical practice. However, due to highly variable cardiac structures across different subjects, it is challenging to obtain an accurate estimation of LV metrics. In this paper, we propose a novel deep learning framework, called cascaded segmentation and regression network (CSRNet), to improve the quantification results. The CSRNet consists of two components: a segmentation component and a regression component. The segmentation component yields myocardial contours of the left ventricle from the input cardiac MR images, and then the regression component learns hierarchical representations from the segmented images and estimates the desired LV metrics. By introducing the myocardial contours, the regression component can pay more attention to the left ventricle, which contributes to more accurate quantification results, although the cardiac structures are variable. The extensive experiments on a dataset of 145 subjects demonstrate that our framework outperforms the state-of-the-art methods.
In this research, an innovative type of sediment resource treatment agent (SRA) was synthesized successfully, which could immobilize ammonia nitrogen (NH
-N), total phosphorus (TP), potassium (K), ...and simultaneously stabilize cadmium (Cd), lead (Pb), chromium (Cr), copper (Cu), nickel (Ni), and zinc (Zn) in dredged sediment. The effects of SRA dosage on stabilizing the nutrient elements and heavy metals were investigated. The results demonstrated that the increase of SRA dosage significantly enhanced the stabilization of nutrients and heavy metals. The 14-day rainwater infiltration and rainwater scouring experiments were carried out. With the simulation test of rainwater infiltration, the stabilization ratios of Cr, Cu, Ni, Pb, Zn, Cd, NH
-N, TP, and K with 2% SRA addition reached 80.8%, 76.8%, 80.3%, 77.5%, 78.0%, 72.7%, 64.3%, 73.9%, and 73.9%, respectively. Under the action of rainwater scouring, the stabilization ratios of Cr, Cu, Ni, Pb, Zn, Cd, NH3-N, TP, and K with 6.4% SRA addition reached 84.6%, 84.0%, 77.6%, 87.3%, 80.0%, 61.5%, 76.2%, 77.8%, and 91.7%, respectively. Therefore, the results demonstrate that SRA is an excellent composite material in stabilizing heavy metals while reserving the nutrients in dredged sediment, thus showing great potential in the application for dredged sediment resource treatment.
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